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竞争监测
Hankang Biotech and Fuhong Hanlin announce strategic collaboration to develop innovative immunotherapies
8On 28 October, Fu Hong Han Lin (2696.HK) and FBD Biologics Limited (" FBD "), the holding company of HanchorBio, have jointly announced a strategic cooperation framework agreement，Both parties will give full play to Hankang Biotech's proprietary multi-functional innovative biologics development platform FBDB™及复宏汉霖贯穿 The integrated biopharmaceutical platform advantage of the whole industry chain of "research, production and marketing", jointly develop new tumor immunotherapies including anti-drug resistance of PD-1/L1 products, and accelerate the expansion of innovative immunotherapy pipeline layout of both parties。Based on the terms of the cooperation, Fuhong Hanlin will enjoy the first option to jointly develop the specified products with Hankang Biotech。
In the future, the two parties will be based on Hankang Biotech's proprietary "FC-based multi-functional innovative biologics (FBDB)™"Platform and Fuhong Hanlin's rich experience in the field of antibody drug development and unique advantages in process development and technology path, joint innovation and joint development of new typesFBDB™The platform combines innovative drugs to further address unmet clinical needs。
（信息来源：复星医药）
Biotechnology company Vaxess Technologies has announced a collaboration with Astrazeneca to develop a potent mRNA patch vaccine
8月24日，Startup Vaxess Technologies has announced a partnership with AstraZeneca to develop a new type of RNA vaccine，It can be administered via a storage-resistant skin patch rather than by injection，Making it possible for patients to use it themselves without having to go through a health care provider，This may make it easier to distribute and administer vaccines in future pandemics。
VaxessMIMIX sustained-release patch technology is being developed。Once placed on the skin, each MIMIX patch delivers a slow-release microarray with bioactive tips into the dermal barrier。These bioactive tips gradually dissolve into the body after the patch is removed, releasing its payload of vaccines and therapeutic drugs over time。
VaxessIn an exclusive interview with Endpoints, Astrazeneca said it has partnered with Vaxess, which could receive up to $10.3 million from Astrazeneca to jointly develop a prototype vaccine for pandemic influenza。
The partnership follows Vaxess '$37 million Series B funding round over the past year and its announcement in June of positive results from a Phase 1 clinical trial of its seasonal flu vaccine patch, VX-103。According to scientists at MIT and Tufts University, the microneedle patch is made with the tip of a silk protein that dissolves in the skin to produce a longer-lasting, more potent immune response。
mRNAVaccines can be quickly designed to match the characteristics of emerging viruses, and the potent, storage-resistant nature of the microneedle patch could be an effective means of combating future pandemics。今年4月，Vaxess公司宣布，The silk protein formula used in its microneedles，Even at 37°C，It also kept the mRNA lipid nanoparticles stable and potent for up to two weeks，This toughness could make the skin patch vaccine easier to use in areas without refrigeration，This is good news for low - and middle-income countries, which generally lack refrigeration facilities, to accelerate the spread of vaccines。
（信息来源：药明康德）
Plus Semaglutide, Novo Nordisk and Thermo Feld entered into a production partnership
8In order to meet the growing market demand for Wegovy, Novo Nordisk has entered into a production partnership with manufacturing contractor Thermo Fisher to produce Wegovy。
According to a Reuters source familiar with the matter, Thermo Feld provides Novo Nordisk with manufacturing services for the Semiglutein-filled injection pens through its CDMO subsidiary Patheon at a facility in Greenville, North Carolina。
The Greenville facility is a multi-purpose pharmaceutical manufacturing facility that covers solid doses, sterile drugs, and secondary packaging。According to Thermo's website, this is Thermo Field's first factory with a fully functional continuous production line。
A spokesperson for Novo Nordisk confirmed that Thermo Fairchild's partnership with Novo Nordisk was launched in April。
That month, Novo Nordisk raised its 2023 revenue growth forecast to 24 to 30 percent from 13 to 19 percent in February。LarsFruergaardJ, CEO of Novo NordiskørgensenDuring the company's first-quarter earnings call in May, the Patheon production contractor helped Novo Nordisk achieve this significant growth。
In early August, Novo Nordisk further raised its full-year sales forecast by 7 percentage points。
According to the press release, Thermo Ferre is Novo Nordisk's second Simeaglutide manufacturing contractor, the first partner being Catalent, but due to various issues with the syringe filling facility, Catalent's delivery of Simeaglutide was temporarily halted at the end of 2021。The Catalent production plant also closed again in August 2022。
In March this year, Semiglutide quickly exploded because of its superior weight loss effect, which was once in short supply。In response, Novo Nordisk in May suspended some promotional activities around Simeaglutide, including television commercials and marketing outreach with healthcare professionals。To control the onset of the disease in new patients, Novo Nordisk's Danish pharmaceutical company has also begun restricting the supply of low-dose semaglutide。
2021At the end of the year, Novo Nordisk announced a 25.The $800 million plan will expand its industrial park in Kalenburg, Denmark, and build three new production sites。The program, which is expected to be completed by 2027, aims to increase the production capacity of Novo Nordisk's active drugs。
（信息来源：药智新闻）
Ai Kai Biology announced the completion of 100 million yuan A++ round of financing
8月28日，Ai Kai Biology announced the completion of 100 million yuan A++ round of financing，This round of financing is led by the original shareholder Zhiyi Investment，西湖科创投跟投，The funds raised will be used for the continuous industrialization of IPscs (induced pluripotent stem cells) that have "erased epigenetic memory.，And clinical advancement of product pipelines for cancer and Parkinson's disease。
Founded in March 2021, Eckbio is focused on the development of superpowered IPSC-derived cell therapeutics。Based on source innovation and industrial transformation capabilities, the company focuses on the field of immune cell therapy and regenerative medicine, and is committed to providing patients with universal, effective and accessible cell therapy drugs。Since its establishment more than two years ago, the company has built the ability of source innovation and effectively promoted the development, transfer and verification of technology in the fields of iPSC, gene editing and stem cell differentiation。
(Information source: 21st Century Business Herald)
Ruilong Nuo Fu announced the completion of nearly 200 million yuan Pre-B+ round of financing
8月30日消息，Ronovo Surgical announced the completion of a Pre-B+ round of financing of nearly RMB 200 million，由纽尔利资本领投，新进投资方翼朴资本跟投，All the old shareholders of the company, Eli Lilly Asia Fund, Weiwu Capital, Matrix Partners, GGV GGV Capital, LRI Jiangyuan Investment, participated in this round of financing。Haoyue Capital acted as the exclusive financial advisor for this round of financing。It is reported that the proceeds of this financing will be used for Ruilongnuo product registration and research and development, to accelerate the landing of modular surgical robots and brand promotion。
Public information shows that Ruilong Nuofu, founded in 2019, is an innovative company in the field of endoscopic surgical robots in China, committed to designing and developing innovative surgical robots for Chinese surgeons that match China's actual clinical needs。The company has assembled a team experienced in the design, development, manufacturing and commercialization of surgical robots, with a core team that has worked for world-renowned medical device or robotics companies。
(Information source: 21st Century Business Herald)
New Open source intends to increase the capital of 50 million yuan Liangyuan Biology, which has the intellectual property rights of the original tumor drug platform
8On the 29th, New Open Source announced that the company intends to sign the "Capital Increase Agreement on Beijing Liangyuan Biomedical Research Co., LTD." with Beijing Liangyuan Biomedical Research Co., Ltd. and its shareholders, agreeing that the company will invest 5000 in Liangyuan Biological in the form of capital increase.1 million yuan, used to subscribe to the new registered capital of Liangyuan Biology 44.64.29 million yuan, the remaining part is included in its capital reserve。Upon completion of the capital increase, the Company will hold Liangyuan Biological 23.81%的股权。
公告显示，The company's main business is the research and development of biomacromolecule delivery systems, oral delivery and therapeutic products based on PEG-PE and PEG-PE derivatives，It owns the intellectual property rights of the original oncology drug platform，In the future, it is expected to achieve the effect of lymph node targeted drugs in the treatment of tumors，It has a good synergistic effect with other cell immunotherapy products invested in by the new open source。The new Open source will obtain the priority cooperation right of the future commercialization of Liangyuan biological products, and under the same commercial conditions, Liangyuan Biological promises the future related production lines and drug marketing authorization holders (MAH) the main landing of the new open source Songjiang base。
（信息来源：智通财经）
Superluminal MedicinesClosed a $33 million seed round and officially came out of hiding mode
Recently, Superluminal Medicines, an AI-generated drug startup, announced the completion of a $33 million seed round of financing and officially stepped out of the hidden mode。RA Capital Management led the round with participation from software venture firms Insight Partners, Nvidia and Gaingels。According to PitchBook, this is the largest seed funding round in biotech this year。
The funds raised will be used to advance its platform and small molecule drug discovery programs targeting high-value GPCRS。
It's a Boston-based AI pharmaceutical company founded by former Schrodinger executive Cony D 'Cruz and RA Capital Management's Ajay Yekkirala。The company focuses on GPCR innovative drug development with the aim of increasing the speed and accuracy of drug production。
Said Andrew Levin, partner and managing director at RA Capital Management, which led the round，Superluminal Medicines combines biology, chemistry and AI technology，Has the potential to accelerate drug discovery and increase the success rate of small molecule drug development。The speed with which the company has moved from prediction to structural validation and seedling compounds is remarkable, and the company is now fully advancing its differentiated candidates。
Cony D 'Cruz, co-founder and CEO of the company, noted that the company's deep understanding of biology and its ability to effectively discover and modlate targets are key competencies and differentiators, and that these sciences and technologies will support the development of innovative therapies。
Founded by former Schrodinger executives to accelerate the development of new GPCR drugs
Superluminal MedicinesThe company is closely related to the experience of co-founder Cony D 'Cruz。
Cony D''CruzHe worked at Schr, a publicly traded company in computational chemistryödingerFor nearly 10 years, he served as the company's Executive vice President and Chief Commercial Officer, managing drug discovery partnerships。在SchrödingerTwo years after going public, Cony D 'Cruz joined venture capital firm RA Ventures as a venture partner。
最初的想法是，As the investment firm becomes more interested in computer-driven drug discovery，Cony D 'Cruz was tapped to help build a drug screening platform for the company's startup incubator，By combining physics-based approaches and machine learning，Helping company-backed biotech startups design and develop drug candidates。
In the process of leading the establishment of the drug screening platform, Cony D 'Cruz had more ideas and considerations。"It's clear that we can do a lot more, and these technologies that we're using can actually operate as a company on their own.。"Cony D 'Cruz recalled。
不久后，Cony D 'Cruz co-founded Superluminal Medicines with fellow RA Ventures colleague Ajay Yekkirala，即“超光速医药”，Reference is made to the concept of faster-than-light speed travel。Ajay Yekkirala, who serves as Senior vice president and head of drug discovery at the newly formed company, is also vice President of Biology at RA Ventures。He is an inventor and entrepreneur in biotechnology with more than 17 years of industry and academic experience in drug discovery and development, as well as extensive experience in financing and management。Previously, he co-founded and served as CSO of Blue Therapeutics, a neurological disease company。
In line with the company's name, Superluminal Medicines aims to revolutionize the speed and accuracy of drug development, using advanced technologies such as AI to reduce the development time of preclinical drug candidate molecules from the years previously required to months。Cony D 'Cruz revealed that the team, now just 10 people, has gone from picking a protein target to designing a compound molecule that targets that protein in five months, and has achieved the expected results in laboratory studies。
According to the website description, Superluminal Medicines focuses on the development of small molecule new drugs that target G-protein-coupled receptors (GPCR)。This is the largest family of cell membrane surface receptors in the human body, with more than 800 family members, and is closely related to many major diseases such as cancer, diabetes, and neurology, and is also regarded as one of the most ideal drug targets。
"There are about 850 GPCRS in the human body, and about 70 percent of them are currently considered 'unpharmaceutical' targets, leaving plenty of room for biotech startups to try to develop new therapies that target these receptors.。We see the opportunity to use AI technology to crack the GPCR drug development challenges and accelerate the drug discovery process。"Cony D 'Cruz said。
The plan is to launch candidate molecules within a few months
Unique AI technology is at the heart of the company's approach to drug discovery, accelerating the development of new drug candidate molecules。Its predict-design-test architecture accurately simulates the shape of proteins and enables the design of highly selective compounds that accurately target structural changes in GPCR targets for better therapeutic outcomes。
AIOne of the core techniques is called free energy perturbation, which is a physics-based method for determining the degree to which a compound molecule binds to its protein target。Accurate prediction of binding free energy is an important direction in computer-aided drug design。
This approach, a core product of Schrodinger's software business, has traditionally required a known protein structure to function。However, the precise structure of most GPCR protein targets has not been fully resolved, and these challenges have plagued drug development for targets such as GPCR。
2021In mid-year, the RA Ventures team began trying to solve these problems using AlphaFold2。AlphaFold2 is an accurate predictive deep learning tool for predicting the three-dimensional structure of proteins from amino acid sequences at a level comparable to laboratory analysis。As the research team used the structure predicted by AlphaFold2 for free energy perturbation calculations, after some tweaks and optimizations, they made important progress in 2022。
In the study, the research team performed free energy perturbation calculations on a well-studied set of protein-ligand complexes and made adjustments and deletions to the training set predicted by AlphaFold2。The study found that, under the right circumstances, the structure modeled by AlphaFold2 is accurate enough to be used for free energy perturbation calculations during the lead optimization phase of the drug discovery process。
Cony D''Cruz"We quickly realized the power of this method to determine not only the structure of GPCRS, but also how these proteins subtly change shape and play different roles.。This detail is crucial for designing selective drugs that can target specific conformations of specific GPCRS with minimal side effects。”
The company is also enhancing its virtual drug screening technology to predict key characteristics of molecules, including their absorption, distribution, metabolism, and excretion (ADME) properties, which describe how the body will dispose of a drug once it enters the body。These properties can make or break a drug when tested in humans。Last year, Superluminal Medicines obtained a large dataset from an undisclosed pharmaceutical company to train its ADME model。
"It is the company's ability to develop novel drug candidates, not just the technology, that determines whether a company will excel in AI drug discovery.。"Cony D 'Cruz said。
At this stage, the company is focusing on GPCR-targeted small molecule drugs, but did not disclose details of the selected GPCR targets or disease areas of focus, or when it plans to advance the first candidates into clinical trials。
Cony D''CruzThe company is accelerating the development of drug molecules and plans to design and develop a lead GPCR drug candidate molecule in the short term (expected in a few months)。
(Information source: Shenghui SciPhi)
Global anti-tumor drug research and development is vigorous
Research and innovation in the field of oncology therapy continues to develop globally, bringing new treatments to patients with advanced cancer and introducing the most advanced science and technology in the field of pharmaceuticals。These therapies represent the largest collective research areas and the direction of the most drug spending。
近日，IQVIA releases Global Oncology Trends 2023:Outlook to 2027，The report reviews the global progress in anti-tumor drug research and development in recent years，Includes key mechanisms, targets, and cancer types being studied，Some emerging fields and trends in drug use are pointed out，The market prospect and drug expenditure of antitumor drugs in the next 5 years are also predicted。
The number of pipelines under development remains historically high
Currently, more than 1,000 companies and nearly 50 academic research institutions worldwide are involved in the innovative development of oncology drugs。Drugs developed by China-based companies now account for 23% of the tumor pipeline, up from 5% a decade ago
The report shows that the number of clinical trials initiated in the field of oncology in 2022 remains at a historically high level, increasing by 22% compared to 2018, mainly in the field of rare tumors and solid tumors。
From the research and development stage, phase II clinical trials (including phase I/II, Ⅱa and Ⅱb) accounted for the largest proportion, 49%;This was followed by Phase I clinical trials (41%).Phase III clinical trials accounted for 10%。
By tumor type, 56 percent of clinical trials focused on rare tumors, but that's down 6 percent from 2021。In terms of tumor form, 75% of trials focused on solid tumors, which is essentially unchanged from 2021。In addition, more than 550 studies targeting blood tumors were initiated in 2022, an increase of 30% compared to 2017。Of course, clinical trials in this area represent only a small fraction of total research。
In terms of research sponsors, emerging biopharmaceutical companies (those with annual sales of less than $500 million and R&D spending of less than $200 million) accounted for 71 percent of the R&D pipeline in 2022, up from 45 percent 10 years ago。At the same time, emerging biopharmaceutical companies are working less and less with large pharmaceutical companies (companies with annual sales of more than $10 billion), only working with large pharmaceutical companies in the later stage of development or even after the drug is on the market。Of these emerging biopharmaceutical companies, 77 percent are focused solely on the development of anti-tumor drugs, and of these, 72 percent are focused on the development of only one drug。Correspondingly, Big Pharma's oncology pipeline has declined, accounting for 21 percent of products currently in development, compared to 36 percent in 2017。
2022Last year, China-based companies accounted for 23% of the oncology R&D pipeline, up from 10% five years earlier and 3% in 2007, overtaking Europe for the first time。These companies' active oncology pipelines have more than doubled in the past five years, indicating that they will play an important role in the development of new products worldwide in the future。
Over the past 10 years, the oncology research and development pipeline has increasingly focused on targeted drugs, and new therapeutic modalities with innovative mechanisms of action have developed rapidly。In the case of PD-1/PD-L1 inhibitors, although the number of pipelines has declined in 2022, the number of related clinical trials initiated in the past five years has increased by as much as 54%。Most ongoing late-stage clinical trials of PD-1/PD-L1 inhibitors are concentrated in a single country, and most are located in China, which means that these drugs are not necessarily targeted for international markets。At the same time, the pipeline of bispecific antibody therapies, antibody-coupled drugs, and next-generation biologic therapies, including cell therapies and RNA cancer vaccines, is growing rapidly。
The number of blood tumor drugs in the pipeline decreased by 4% in 2022 compared to 2021, while the number of solid tumor drugs in the pipeline increased by 5%。The market in the field of tumor immune agents has begun to become crowded, and it is inevitable that companies will change their research and development strategies and turn their attention to other newer targeted molecules。
中国临床试验活跃
Over the past 10 years, the number of products in development in the field of oncology has grown significantly, with more than 2,000 products currently in development。New therapeutic models with innovative mechanisms of action are developing rapidly。
2015The overall success rate of cancer drug development has been on a downward trend since last year, falling to 3 in 2022.5%。Oncology drug trials are much more complex than other disease areas in terms of the number of eligible patients, clinical trial endpoints, and research centers。Moreover, the "gap period" (that is, the time difference between the duration of a clinical trial and the trial phase) for oncology drugs is much smaller than in other therapeutic areas, but the trial duration is longer。Although the clinical development productivity of rare cancer drugs is high, the overall productivity of oncology drug research is the lowest of all therapeutic areas, based on their success rate, complexity, and duration。
It is worth mentioning that the number of clinical trials conducted in China is gradually increasing。More and more clinical trials are being conducted outside the United States。Although the average number of research centers in other countries and regions is smaller, the number of subjects per research center is constantly rising。In 2022, 57% of clinical trials will be conducted outside the US, up from 42% 10 years ago.In the same year, China alone accounted for 57 percent of trials conducted outside the United States, up from 12 percent in 2013, reflecting the growth in clinical trial activity in China。
Key research and development trends in oncology include the emergence of innovative therapeutic modalities and targets，New types of molecules and targeted therapies are being used to treat patients with more early-stage cancer，Innovative combination therapies to overcome drug resistance，A new generation of tumor immune targets other than PD-1/PD-L1 inhibitors has attracted attention，Clinical progress and validation of mRNA cancer vaccines，There is also an increase in the clinical use of subdividing patients based on biomarkers and liquid biopsies。
新成果更好惠及患者
Many new oncology drugs have demonstrated significant clinical value over the past 10 years, but patient access and use varies widely across countries and regions。
2022A total of 21 new active anti-tumor substances (NAS) were launched globally, down from the previous record of 35 launched in 2021。In the past five years, 115 new anti-tumor active substances have been marketed worldwide。Since 2003, a total of 237 new active anti-tumor substances have been listed worldwide。Although these drugs are not available in all countries and regions, most countries and regions have made some important breakthroughs in tumor immunology, and the use of precision biomarkers has become the standard therapy for many tumors。
It is worth noting that 75 new oncology drugs were launched in China in the last five years, compared with 46 between 2003 and 2017。This is due to the reform of the review and approval system of China's drug regulatory authorities, which enables Chinese patients to have faster access to innovative drugs developed at home and abroad。
Despite significant advances in cancer treatment worldwide, there are still differences in the resources and care available to cancer patients across countries and regions。
The number of cancer patients treated worldwide has increased by an average of 5% over the past five years and is expected to accelerate over the next five years as the use of new drugs expands further。Even so, progress in bringing novel anti-tumor therapies to patients varies across countries and regions, including rates of biomarker detection, adoption of novel therapies, and infrastructure capacity to deliver state-of-the-art therapies。
In the last five years, the treatment of non-small cell lung cancer has begun to shift - with PD-1/PD-L1 inhibitors and kinase inhibitors as the standard of care, resulting in an extension of the median sustained response time of first-line therapy by nearly 1 year。With the wider use of new therapies, gynecological oncology and multiple myeloma drugs have also made advances, improving the effectiveness of patient treatment。The use of a new generation of biologic therapies, including cell and gene therapies, in cancer treatment continues to grow。
Since 2020, the number of experienced CAR-T cell therapy research centers around the world has been increasing, reaching 1,791 in 2022, of which 360 are located in China, which means that a large number of innovative research on CAR-T therapy is being carried out in China。At the same time, the number of accredited research centers has grown from 386 in 2020 to 532 in 2022, which means that more CAR T cell therapies are approved and patient access to treatment is also increasing。However, due to geographical location and product availability, those patients who do not have the conditions to travel long distances are still unable to access treatment。
美国仍是全球最大市场
2018Global spending on oncology drugs will grow from $129 billion to $196 billion in 2022, a compound annual growth rate of 12%.It is expected to reach $375 billion by 2027, with a compound annual growth rate of 13 percent.8%。
2022Global spending on oncology drugs reached $196 billion last year and is expected to reach $375 billion by 2027。Spending growth was driven by continued innovation, partially offset by adoption of biosimilars in major markets。The United States remains the world's largest market for antitumor drugs。
In the past five years, China's spending on oncology has grown by $6.8 billion, mainly due to the popularity of new therapies and an increase in the number of brands, but partly offset by drug control fees。Globally, seven of the top 10 oncology treatment areas have seen double-digit spending growth over the past five years, driven by the shift to early treatment lines of new drugs and novel therapies, including PD-1/PD-L1 inhibitors。
The new generation of biological therapies for cancer holds great clinical and commercial potential, but there is also considerable uncertainty, with global spending on cell, gene and RNA therapies likely to grow from $3 billion today to $19 billion by 2027。Expanding the use of these therapies to include new indications, adding existing cell therapies to earlier stages of treatment, and continuing to improve safety and efficacy could cost as much as $50 billion。
（信息来源：中国医药报）
Innovative pharmaceutical companies aim at the layout of tens of billions of large varieties, how to avoid the problem of high risk of "source" investment？
Lung cancer is the malignant tumor with the highest morbidity and mortality in China, and EGFR is the most common type of driver gene mutation in NSCLC。EGFR Exon20ins mutation is a rare type of EGFR mutation, accounting for about 12% of EGFR mutations. Due to its special spatial configuration and strong heterogeneity, safe and effective targeted therapies have been lacking for a long time, and the survival benefit of patients is short, which is a clinical pain point that needs to be solved urgently。
From 2016 to 2020, China's EGFR small molecule targeted drug market grew from 2.2 billion yuan to 10.8 billion yuan, with the popularity of genetic testing technology and medical insurance access speed, relevant institutions predict that by 2025, China's EGFR small molecule targeted drug market size will reach 36.8 billion yuan。The ability of EGFR small molecule targeted drugs to attract money is obvious to all, and in 2022, Astrazeneca's global sales of Ocitinib reached nearly 5.5 billion US dollars。
In this ten-billion-level track, there is still a large number of unmet needs, and many pharmaceutical companies want to become the next ocitinib。
近日，Local innovative pharmaceutical company Dizhe Pharmaceutical announced，Its first self-developed new lung cancer targeting drug, Suvotinib, was officially approved by the National Medical Products Administration (NMPA)，For disease progression after previous platinum-containing chemotherapy，或不耐受含铂化疗，Patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with exon insertion mutations in epidermal growth factor receptor (EGFR) No. 20 were confirmed by testing，Become the first national innovative drug for EGFR exon20ins mutant advanced NSCLC。
At present, there are also many pharmaceutical companies in the layout of EGFR Exon 20ins mutation, such as Re Ding Pharmaceutical, Jun Jing biological and saddle stone biological, and Dizhe Pharmaceutical project earlier。
Zhang Xiaolin, chairman and general manager of Dizhe Pharmaceutical, said in an interview that Dizhe Pharmaceutical has discovered the unmet need for EGFR exon20ins mutations before other companies in the world, and in this direction, there is great hope to develop a new generation of small molecule targeted drugs。At the beginning of the project, the EGFR exon20ins mutation received little attention。
根据公开信息，Digitalpharma was formerly known as Astrazeneca's Asia Research and Development Center，Operated independently in October 2017，Founder Zhang Xiaolin previously led and participated in the global R&D strategic layout of Astrazeneca，Led the team to discover the resistant mutation T790M of Iressa，在此基础上，立项了泰瑞沙的研发，The product remains Astrazeneca's best-selling drug。
肿瘤药源头创新难
The field of oncology has always been the focus of new drug research and development，从2016年开始，The proportion of tumor field is more than 50% year by year，The early development of products are still dominated by me-too products，But in recent years, with the improvement of research and development strength，The model of innovative drug development is also changing，Products with FIC (first-in-class) potential continue to emerge。
Of course, this trend shift can not be generalized, China's true sense of the world's first drug is still insufficient。In the field of small molecules, the selectivity difference of kinases may lead to the emergence of multi-target drugs, thus improving the drug data of FIC.In the field of antibodies, with the advancement of technology, the combination of dual-target and multi-target antibodies has also increased the number of FIC drugs to a certain extent。
Zhang Xiaolin said that pharmaceutical research and development must avoid the "inner volume", dozens of hundreds of companies in the hot target research and development phenomenon is not desirable, it is not worth putting money and life into a lot of simple Me-too。This is also why five or six years ago, when many companies gathered PD-1/L1, we began to select the unnoticed exon20ins mutation as a target。
在靶点的选择上，Thomas Suderhoff, winner of the 2013 Nobel Prize in Physiology or Medicine, said，The biggest challenge in drug development is finding targets that are druggable，换句话说，Drugs can be developed against this target，And it has relative disease specificity，So that when a drug for that target comes along，To really help people who are suffering from certain diseases，如果不想靠运气找到靶点，Meeting this challenge requires a deep understanding of disease biology and the biological processes involved。
根据公开信息，At present, the clinical first-line treatment for this target is still mainly chemotherapy，Third generation EGFR small molecule targeting drugs，Immunotherapy has attempted to overcome the EGFR Exon 20ins mutation，但都没有取得明显的效果，因此，There is still a large unmet medical need in this area。
To this end, there are also many pharmaceutical companies in the layout of EGFR Exon 20ins mutation, such as Re Ding Medicine, Jun Jing biology and saddlestone biology, etc., due to the early project, research and development efficiency, Dizhe Medicine's Suvotinib ran the whole course at the fastest speed。
"Of course, choosing rare targets and focusing on source innovation is not cheap, and wanting to take shortcuts will add additional risks to enterprises.。The concept of Biotech in China and the United States is very different. The United States only focuses on innovation. Many companies only have one main product and the follow-up product pipelines are embellished, but this product often has its own unique features。If it works out there's a big takeover soon, if it doesn't work out there's no sense it's over。Zhang Xiaolin said that the concept of China's pharmaceutical investment is that it wants to innovate and do not want to lose money, which requires risk control。
Zhang Xiaolin pointed out that local Biotech companies need to manage risks from the product line, especially focusing on the areas they are familiar with, only in this way can they ensure early success and survival。"We chose to prioritize Suvotinib and Golicitinib due to the team's previous experience with Astrazeneca's gefitinib and osiecitinib。Based on our accumulation in the EGFR field, we quickly completed the dosage climb in preclinical studies, and at this point, we felt that the likelihood of success was very high, so as to push suvotinib into the clinic as quickly as possible。”
把控研发风险
Because many market-oriented capital is more willing to invest in products with clear targets and can be quickly marketed, China's basic research strength is still weak。
The report "Promoting Innovation in China - Best International Practices" issued by the World Bank makes nine specific recommendations, including strengthening basic research and investment。The NIH and NSF are responsible for 60% of the annual funding for basic scientific research。This compares with 17% of OECD countries in 2017&D invested in basic scientific research, while China's less than 5%。
At present, most capital and enterprises have to give up the rush for quick success, and instead pay more attention to the long-term layout of research and development, strengthen basic scientific research and investment, and develop new mechanisms and new targets。In this way, innovative drug companies are forced to avoid homogenization competition, strive to move towards the stage of "original innovation", strengthen the research and development of "First-in-class" innovative drugs, and pay attention to the research and development of important varieties that do not meet the requirements。
"Source innovation" is not easy, which also requires enterprises to do a good job in advance of the corresponding R & D risk control, in this regard, Zhang Xiaolin suggested that we need to pay attention to three dimensions:
一是时间维度。For example, for the "great innovation" in the concept, the results may not be seen until 10 years later, and this kind of innovation needs to be carefully selected for start-ups, and there must be a time to promote the plan;
二是科学分析维度。As long as the third phase of clinical work is not completed, the risk will not be fully exposed, so it is necessary to scientifically control the risk, and not all bet on the same target and the same principle.
三是资金管理维度。In many cases, Biotech does not have no money, but does too many things, so companies need to plan their funds properly and focus on competitive areas。
"In our view, risk management needs to be done through a reasonable balance。Our first goal is as soon as possible in the scientific more secure products, as soon as possible to market, to achieve self-hematopoietic。At the same time, in the early stage, we chose to focus on the field of oncology, but we also realized that the field of oncology is not only in China, and over the past 20 years, more and more companies around the world have chosen this field, making the track very crowded。Therefore, in my opinion, the field of cancer needs the next breakthrough, after all, from the perspective of tumor in a large field, from chemotherapy, radiotherapy, targeted therapy, immunotherapy, etc., has gone to an extreme, and the treatment direction is becoming more and more detailed。
这也是由于，一方面，对患者而言，The advent of personalized therapy (CAR-T) has made tumor treatment more and more accurate，Clinical selection Clinical design based on individual patient needs，But these drugs are also more expensive，这也意味着，It is necessary to strike a balance between R&D and revenue;On the other hand，From early chemotherapy to today's targeted therapies，甚至是个体化治疗，下一步，Science will also shed new light on the most fundamental theories，这是一个螺旋上升的过程。
"All projects have risks, but as a business we will never do Me-too。那怎么办？This requires us to trust the science, according to the data of science, although it is still possible to fail, if we do not follow the science, then we are doomed to fail。Therefore, we should make science solid and do what should be done according to science, "Zhang Xiaolin stressed。
国际化需“因人而异”
From an industrial point of view or from a capital point of view, the current stage is considered to be the beginning of a new cycle in the pharmaceutical industry, after a bubble, the tide receded to know who is really naked swimming, a real group of excellent companies can begin to cash in growth, a group of globally competitive companies, began to show。
Therefore, at this point, it is still a very good time to invest in biological drugs, and it is also under the pain point of market development, how to find the right development path has become the focus of the current innovative drug companies。For this reason, Biotech companies that had only focused on the Chinese market began to grasp the international market opportunities, hoping to avoid market risks to the greatest extent。
In the development of the pharmaceutical industry in the past few years, as a domestic innovative drug company, based on China for the global market has become the consensus of the industry。From the perspective of investors, they want to explore more globally competitive enterprises and innovation pipelines, but internationalization is not an overnight success。In the past two years, there have also been domestic innovative drug companies ready to take the domestic clinical phase III data directly to FDA declaration, which was directly rejected by the FDA and broke the overseas market。
Many analysts believe that in this case, it can be noticed that the valuation of many companies around the capital is much higher than the value of the enterprise itself, so it is inevitable that the fall will happen。Especially in the past two years, we have also observed that innovative drugs are risky assets, the research and development cycle is relatively long, the investment is relatively large, and will definitely be affected by internal and external factors such as the interest rate environment。
This also requires all Biotech companies to do a good commercial layout。When it comes to commercialization, we have to focus on the topic of "going to sea". At present, many Biotech companies believe that the internationalization of "going to sea" can strengthen the hematopoietic function of local innovative pharmaceutical companies。张小林有更深刻的见解。He points out that going "out to sea" is not for all Biotech companies。If you want to do source innovation, you must be able to get first-hand market feedback，In this way, we can really understand the clinical needs，目前的治疗手段中，需要改进的地方，We need to have front-line information to feedback on our own products，This is the new development of these new ideas, new targets，新的手段至关重要，
"So we have our own commercialization team in China, and the overseas market, although the current measurement of the success of the commercial layout is' going to sea ', especially we do not see many Biotech companies successfully 'going to sea' business cases.。Every enterprise should clearly consider the purpose of "going to sea"。Zhang Xiaolin said that if the purpose of "going to sea" is to gimmicks, or to attract investment, it is not advisable。
In fact, compared with previous years, it can be found that the overall progress of domestic innovative drugs "going to sea" has slowed down recently。不少企业也愈发认识到，Want to achieve the smooth "sea" of products，一方面，There is a real clinical unmet need to be tapped，Develop truly differentiated competitive advantage products，Avoid being involved in homogeneous competition;On the other hand，Preclinical and clinical studies need to be done，加快海外临床，靠科学数据说话，Increase the likelihood of successful commercialization of the product。这也是行业良性发展方向。
(Information source: 21st Century Business Herald)
Dang Dang fast medicine released the strategy of thousands of cities and millions of stores, and laid out the national pharmacy alliance
8On October 28, Dingdang Fast Medicine, a subsidiary of Dingdang Health, a listed company in Hong Kong, released a strategy of thousands of stores and laid out the national pharmacy alliance。As the first landing support of the new strategy, Dingdang Fast Medicine "one-stop digital intelligence omni-channel solution" was released。
Individual pharmacies are facing structural competition pressure from the market。According to a recent report from Guohai Securities, the number of pharmacies in China is steadily expanding, with a growth rate of more than 5% since 2018, and the number of retail pharmacies in the country will reach 62 by 2022.3万家。At the same time, the chain rate of national pharmacies is also rapidly improving, and the national chain rate of pharmacies will reach 57 in 2022.By 2025, the figure is expected to be close to 70%。
Compared with chain pharmacies, individual pharmacies face difficulties such as weak bargaining power with upstream suppliers, higher relative unit management costs, and insufficient brand influence。机遇与挑战并存。CMH data show that from 2015 to 2022, the overall sales scale of retail pharmacies in China maintained steady growth, and the sales scale in 2022 has reached 542.1 billion yuan, and the proportion of drug sales in physical pharmacies has increased significantly。The reason is that after 2018, the national drug collection continued to develop, compressed the overall drug market size, and the products that failed to win the bid in the hospital turned to outside channels。
At the same time of releasing the strategy of thousands of cities and thousands of stores and laying out the national pharmacy alliance, Dingdang Fast Medicine jointly empowers tens of thousands of pharmacy terminals from the four directions of drug supply chain, digital infrastructure, platform service and operation empowerment with "one-stop digital intelligence omni-channel solution"。
（信息来源：新京报）
How to improve the success rate of anti-tumor drug development
The research and development of novel anti-tumor drugs has high cost, high failure rate and challenging process。最近，The JAMA subsidiary journal JAMA Network Open published an article analyzing the status of the development of insulin-like growth factor-1 receptor (IGF-1R) inhibitors，并以此为例，The challenges in the clinical transformation of antitumor drugs were analyzed，And potential ways to address these challenges。
At the beginning of this century, due to the key role of IGF-1R in cell proliferation, growth and survival, drug developers have developed a strong interest in it and have invested in this field for new drug research and development。The paper states that 16 IGF-1R inhibitors are available in nearly 1.A total of 183 clinical trials have been conducted on 20,000 patients, yet not a single drug has received regulatory approval for clinical use in cancer。The cost of these tests is estimated at $1.6 billion。
更为关键的是，Published preclinical data based on in vivo animal trials (hereinafter referred to as in vivo preclinical data)，Half showed that IGF-1R inhibitors inhibited tumor growth by less than 50%，This further suggests that the quality of preclinical study data may be a key factor in the high failure rate of antitumor drugs。By analyzing the factors that lead to drug development failures, the authors also hope to find strategies to improve the success rate of anti-tumor drug development and ultimately benefit patients。
新药研发的惊人投入
This study uses a cross-sectional design to explore the cost and causes of clinical translational failure in the development of anti-tumor drugs, using the IGF-1R inhibitor development process as a case study。To that end, the researchers dug deep into PubMed and ClinicalTrials.gov, a public database, identified clinical trials of IGF-1R inhibitors for oncology treatment between January 1, 2000, and July 31, 2021。
Studies have shown that 16 therapies that work primarily by inhibiting IGF-1R have entered clinical studies, and their therapeutic modalities include small molecule drugs, combination cell therapies and antibodies。According to the data, 183 clinical trials have been conducted under these IGF-1R inhibitor-based treatment strategies, involving a total of about 1.20,000 patients, and the overall cost is estimated at more than $1.6 billion。
Further data analysis revealed that the number of clinical trials of IGF-1R inhibitors fluctuated between 2000 and 2015 based on their trial phase (phase I to III)。The first Phase I clinical trial of the IGF-1R inhibitor figitumumab was initiated in 2003, and the first phase III clinical trial was initiated in 2008。From 2003 to 2009, the number of trials launched each year continued to rise, but then the number began to taper off and fell sharply from 2013。
Notably, the study also noted that about half of published in vivo preclinical data showed that IGF-1R inhibitors were less than 50% effective in inhibiting tumor growth。This suggests that the lack of preclinical evidence may be one of the key factors in the high failure rate of clinical trials of antitumor drugs。
失败原因究竟为何
The study points out that the poor performance of IGF-1R inhibitors in clinical trials is mainly due to their lack of sufficient clinical efficacy - a necessary condition for regulatory approval of oncology treatment。In trials conducted by any pharmaceutical or biotechnology company, IGF-1R inhibitors have failed to show significant clinical benefit against tumors。
These findings shed light on potential core problems in clinical trials。For example, when the IGF-1R signaling pathway is inhibited, other alternative pathways may be activated to take over its function。In addition, the underuse or inappropriate use of predictive biomarkers in selecting subjects for clinical trials may also be a contributing factor。Through in-depth retrospective analysis, the researchers concluded that the failure of clinical trials is closely related to the lack of biomarker-based utilization strategies。
Regarding the preclinical models used in the development of IGF-1R inhibitors, some have argued that they fail to accurately capture the core features of the disease or provide effective guidance for the decision to advance drug candidates to clinical trials。For example, data on single drug activity in vivo from xenograft models showed inconsistencies, with half of the studies showing tumor growth inhibition rates of less than 50%。
In addition, most studies did not consider the recurrence of tumors after treatment ended。Although the in vivo data at the preclinical stage of the study appear convincing, there is no conclusive evidence that IGF-1R inhibitors achieve long-term therapy in tumor-bearing mouse models。Although some researchers believe that xenograft model data can predict the clinical performance of IGF-1R inhibitors, to date, these inhibitors have not demonstrated a clear therapeutic effect in clinical trials。Therefore, the main focus should now be on more rigorous validation of targets and further optimization and improvement of preclinical models。
From the perspective of drug development costs, this study found that 183 IGF-1R trials generated a cumulative R&D cost of 16.3亿美元。In the pharmaceutical industry, about $50 billion to $60 billion a year is invested in anti-tumor research and development projects that may ultimately fail。Due to the high intensity of trials in oncology, many trials may be repetitive and may even be unnecessary。This phenomenon may be related to excessive expectations for new drugs, increased competition in the industry, and continuous pressure to constantly update the drug development pipeline。
Regarding this phenomenon of a lot of "copycat research" in a hot area in a short period of time, Dr. Arthur Suckow, founder and CEO of DTx Pharma, has pointed out that "many companies are doing the same thing in different places.。I don't know how it would be integrated, but it would lead to inefficient use of funds because there is a lot of duplication of work being done。”
In the future, it will be a meaningful research direction to conduct in-depth research on the costs and results caused by competition in the field of oncology。
提升研发成功率有策略
From the experience of the IGF-1R inhibitor project，There are at least three important lessons for researchers，Anticancer drugs should undergo rigorous evidence screening before development;secondly，技术应保持多样化，To avoid over-reliance on a particular mechanism;finally，当临床研发失败时，应进行深入的原因分析。
There are also some factors that can not be ignored on the efficiency of new drug development。Laksh Aithani, founder and CEO of CHARM Therapeutics, emphasizes the importance of data sharing，他认为在临床前研究阶段，更好地收集数据，And it will be sorted out, standardized and integrated，Sharing data between different companies and academia can make research and development more efficient。In addition, facilitating the close cooperation of the staff of the research and development team is also considered by some in the industry to be one of the starting points for improving the efficiency of research and development in the pharmaceutical industry。Dr. Jeffrey Bluestone, CEO of Sonoma Biotherapeutics, spoke about how to improve the efficiency of new drug development，R&d efficiency and industry productivity in general depend on two things - what is the treatment model being developed and how is it being tested，R&d efficiency is actually the link between research and development。In his view, the more closely we can get researchers, early-discovery scientists and manufacturing teams to work together, the more effective and reliable treatments will be developed。
Finally, the inadequacy of preclinical models undoubtedly affects the success rate of new drug development。Josh Mendel-Brehm, CEO of CAMP4 Therapeutics, emphasized the important role of preclinical models in the development of new drugs。Drug discovery and development begins with the identification of a target, followed by researchers designing the drug and testing it in as many models as possible, before moving on to clinical trials that fundamentally validate the initial hypothesis, he said。Therefore, in his view, the emergence of biological models, tissue chips, or other models that more closely resemble real human situations and can more accurately predict the effects of drugs in the human body is very valuable。If you can have a higher success rate from the start, there is no need to pursue second -, third - or fourth-generation drugs。Therefore, efforts should be made to ensure success on the first try。He believes that better clinical trial design and more advanced research methods will help。
In summary, by exploring the barriers to clinical translation of new drug molecules and the costs of research and development, we can not only more intelligently screen out high-potential drug candidates, thereby improving research and development efficiency, but also help to innovate and improve research and development strategies。The core of these strategies is to enhance target validation, optimize preclinical trial models, increase the diversity of drug forms and technical approaches, and allocate research and development resources more efficiently。Implementing these strategies is expected to significantly reduce mortality from major diseases such as cancer, reduce the failure rate of clinical trials, and avoid exposing patients to potential drug toxicity。
（信息来源：中国医药报）
Hengrui Pharmaceutical announced the latest research results of "double AI" combination of nasopharyngeal cancer
8On the 28th, Hengrui Pharmaceutical announced that the clinical study results of the innovative drug carrilizumab combined with Apatinib (" double ai "combination) in the treatment of recurrent or metastatic nasopharyngeal cancer were published in Nature Communications, a sub-journal of Nature。The study was led by Professor Haiqiang Mai of the Nasopharyngeal Department of Cancer Prevention and Control Center of Sun Yat-sen University。Results of the study showed that the objective response rate (ORR) of carrellizumab combined with apatinib in second-line treatment of recurrent or metastatic nasopharyngeal carcinoma was 65% in patients progressing with first-line platinum-containing chemotherapy (cohort 1) and 34 in patients progressing with first-line immunotherapy (cohort 2).4%, and the overall safety of the combination therapy was good。
The press release of Hengrui Medicine said that this is another exploratory breakthrough in the treatment of multiple cancers in the combination of "double ai", which is expected to bring new treatment options for patients with recurrent or metastatic nasopharyngeal cancer。In July this year, the research results of "double ai" in the treatment of liver cancer were published in the main journal of the Lancet, an international medical journal, and its U.S. listing application was accepted by the FDA。
According to the literature, nasopharyngeal carcinoma (NPC) has unique geographical, etiological and biological characteristics that distinguish it from other head and neck tumors。Patients with recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) typically have a poor prognosis, with a median overall survival of about 20 months。Cisplatin combined with gemcitabine is the standard first-line chemotherapy regimen for RM-NPC。Immunotherapies, particularly PD-1/PD-L1 inhibitors, have shown therapeutic efficacy in various cancers as well as in RM-NPC in recent years。The Chinese Society of Clinical Oncology (CSCO) Clinical guidelines recommend carrilizumab in combination with gemcitabine as first-line treatment for patients with RM-NPC。There are few treatment options for patients who are refractory or progressive after treatment with chemotherapy combined with PD-1 inhibitors, and there is currently no standard treatment。
According to a press release from Hengrui Medicine, carrilizumab is a humanized anti-PD-1 monoclonal antibody that has been approved for nine indications in five tumor species: lung cancer, liver cancer, esophageal cancer, nasopharyngeal cancer and lymphoma。Apatinib is a small molecule tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR) and is currently approved for three indications。The combination of PD-1/PD-L1 inhibitors with anti-angiogenic agents has shown promising efficacy against a variety of malignancies。From a mechanism point of view, anti-angiogenic drugs can directly reduce the proliferation of regulatory T cells by increasing the normalization of blood vessels, increase the infiltration of immune effector cells into the tumor, promote dendritic cell maturation, and reshape the tumor microenvironment。Anti-angiogenic drugs can increase the density of small veins in the tumor microenvironment, promote T cell transport to the tumor, and overcome the endothelial immune cell barrier。
The study, published in Nature Communications, is an open-label, two-cohort, single-center phase 2 clinical trial。The main entry criteria of the experiment were: 18-75 years old，Histologically or cytologically confirmed recurrent/metastatic nasopharyngeal carcinoma，不适宜接受局部治疗，ECOG Fitness status score is 0 or 1，First-line progression after receiving platinum-containing chemotherapy (cohort 1) or immune checkpoint inhibitor treatment with or without platinum-containing chemotherapy (cohort 2)，Have at least one measurable lesion;Subjects who had received VEGFR-targeted therapy were excluded。The primary endpoint was objective response rate (ORR), and secondary endpoints included disease control rate (DCR), progression-free survival (PFS), duration of response (DoR), and safety。
2020From September to January 2021, a total of 72 subjects were enrolled, including 40 in cohort 1 and 32 in cohort 2。As of October 2022, the median follow-up time in cohort 1 was 23.At 3 months, the ORR was 65%, the DCR was 80%, and the median PFS was 12.Six months later, the median OS was not reached。The median follow-up time in cohort 2 was 18.5个月，ORR为34.4%，DCR为68.8%，中位PFS为4.5个月，中位OS为16.2个月。The results of this study suggest that carrilizumab combined with Apatinib has good antitumor activity in patients with refractory recurrent/metastatic nasopharyngeal carcinoma who have failed first-line therapy。
The press release of Hengrui Medicine said that this means that the exploration of "double ai" in the treatment of multiple cancers has taken another step。In recent years, Shuangai has been studied in different tumor species such as liver cancer, esophageal cancer, stomach cancer, melanoma, endometrial cancer and lung cancer, respectively, and has achieved positive results and appeared on the international stage。In the future, "Shuangai" will continue to explore a wider range of cancer treatments to benefit more cancer patients。
（信息来源：医药观澜）
一年平均减重13.3%, Novo Nordisk announces Phase 3 clinical results of Simeaglutide in heart failure
8Novo Nordisk today presented data from a Phase 3 STEP HFpEF study of Semaglutide。
The study results showed that semaglutide 2.4mg was superior to placebo in reducing symptoms and physical limitations in obese and heart failure patients with ejection fraction retention (HFpEF)。
In the STEP HFpEF study, where semaglutide was administered once a week for more than a year, patients lost an average of 13 pounds.The average weight loss in the placebo group was only 2.6%。
In addition, Semaglutide significantly improved patient scores on the Kansas City Cardiomyopathy Questionnaire, which is a measure of symptoms and physical limitations of HFpEF。
According to the findings published in the New England Journal of Medicine on the same day, GLP-1 agonists also improved motor function and weight loss in patients to a greater extent。
HFpEFThe symptoms of the patient are normal myocardial contraction, but the diastolic function of the heart ventricles is impaired。In patients with lower ejection fraction, the heart muscle does not contract normally。Both conditions result in reduced blood flow。
In a recent press release, Novo Nordisk noted that HFpEF is the most common type of heart failure, accounting for 50% of all heart failure cases, and about 80% of HFpEF patients are overweight or obese, with symptoms associated with increased burden of symptoms, decreased physical function and lower quality of life。
STEP HFpEFDr. Mikhail Kosiborod, the trial's lead investigator, said in a statement，The positive results of the Simeaglutide Phase III trial for heart failure indicate a fundamental paradigm shift for cardiologists in selecting potential treatment options for obese people with HFpEF，It is expected to provide new treatment options for patients with HFpEF，Especially for overweight or obese patients。
In addition, Yigal Pinto, MD, another participant in the trial, added that how these findings translate into endpoints remains to be determined, but will be critical to determine the role of GLP-1 excitatory action compared to SGLT2 inhibition in heart failure patients with ejection fraction preservation。
Novo Nordisk has previously reported that semiglutide can reduce the risk of cardiovascular events in obese people by 20%，除了减肥外，Semaglutide has favorable effects on a variety of metabolic and hemodynamic disorders common in HFpEF obesity phenotype，These include insulin resistance, inflammation and high blood pressure，在2型糖尿病患者中，Semaglutide reduces the risk of MACE，Not only has its cardiovascular safety been demonstrated，还证明了其心血管优势。
（信息来源：药智新闻）
Astrazeneca applied for clinical application of 2 new anti-tumor drugs in China: ADC and PARP inhibitors
Recently, according to the CDE official website, Astrazeneca's clinical application for two Class 1 new drugs was accepted。AZD5335, a new FRαADC drug, and AZD5305, a PARP1 inhibitor。
7At the end of the month, according to Astrazeneca's 2023 semi-annual report, its blockbuster HER2ADC drug Enhertu (DS-8201) sales reached 11.$6.9 billion, up three times from a year earlier。今年的ASCO会议上，Astrazeneca and Daiichi SAN announced two clinical results，The DESTINY-PanTumor02II trial was designed to evaluate the efficacy and safety of Enhertu in patients with locally advanced, unresectable or metastatic, previously treated HER2-expressing solid tumors that do not qualify for curable therapy，The results showed that DS-8201 has a certain effect on biliary tract cancer, bladder cancer, cervical cancer, endometrial cancer, ovarian cancer, pancreatic cancer and rare cancers。
As indications expand, it may only be a matter of time before Enhertu becomes a billion-dollar product。
At the same time, Astrazeneca is also actively promoting other ADC products in its pipeline。The AZD5335 is Astrazeneca's third self-developed ADC。The drug consists of a targeted FRα antibody coupled with a TOP1i payload (AZ14170132) with a DAR of 8。
At this year's AACR meeting, Astrazeneca first revealed AZD5335 research data in the form of the LateBreakingPoster (LBP) : AZD5335 (2.5mg/kg,IV,SD）在卵巢癌细胞系异种移植（CDX）中肿瘤生长抑制（TGI）为75%-94%；在评估的14/17（82%）卵巢癌患者的异种移植模型（PDX）中，中位最佳肿瘤皱缩>30%。In two PDX models with low - to medium-frα expression at the same or higher dose, AZD5335 had superior preclinical activity than a targeted FRαADC based on a microtubule inhibitor (MTI) payload。
AZD5305It is Astrazeneca's second PARP1 selective inhibitor, which was first declared clinically in China in 2021。In 2022, AZD5305 will initiate clinical trials in China to conduct an international multi-center Phase I/IIa clinical trial in patients with advanced malignant tumors to evaluate the safety and efficacy of AZD5305 as dose-increasing monotherapy and in combination with anti-cancer drugs。
Astrazeneca already has several PARP inhibitors。The world's first PARP inhibitor, Olapalil, was developed by Astrazeneca, and since its approval in 2014, its sales have soared, reaching 26 percent worldwide in 2022.38亿美元。However, olapalil has some side effects, and the patent for the compound will expire in March 2024。
AZD5305As Astrazeneca's second PARP1 selective inhibitor, it is expected to overcome the side effects of Olapalil and become a "successor".。Studies have shown that AZD5305 is better tolerated than first-generation PARP inhibitors in patients with ovarian, HER2-negative breast, pancreatic and prostate cancers with BRCA1/2, PALB2 and RAD51C mutations。
At the same time, Astrazeneca is still actively expanding the indication of Olapalil and deploying a new brain-penetrating PARP1 inhibitor, AZD9574。
小结
2023Astrazeneca's China revenue reached 30 percent in the first half of the year.$4.3 billion, up 9 percent from a year earlier。In its earnings report, Astrazeneca also expects three new drugs to make new progress in China。Under the accelerated state of innovation, Astrazeneca may achieve more breakthroughs in the second half of the year。
（信息来源：药智新闻）
Keep your cholesterol down for 6 years!Novartis announces positive data from Phase 3 trial of PCSK9 targeted siRNA therapy
Novartis today announced new long-term data from its Phase 3 clinical trial of ORION-8。数据表明，Its twice-yearly RNAi therapy Leqvio (inclisiran) plus statin therapy，Sustained low density lipoprotein cholesterol (LDL-C) reduction for more than 6 years in patients at increased risk for atherosclerotic cardiovascular disease (ASCVD), ASCVD, or heterozygote familial hypercholesterolemia (HeFH)。Detailed results were presented at the European Society of Cardiology (ESC) 2023 annual meeting。
Over time, atherosclerotic lesions occur gradually due to the accumulation of lipids, and the main culprit is the low-density lipoprotein cholesterol in the inner wall of the arteries。Unplanned rupture of atherosclerotic plaque can lead to atherosclerotic cardiovascular events such as heart attack or stroke。Events due to ASCVD, including heart attacks and strokes, account for 85% of all cardiovascular disease deaths。Many patients with elevated LDL-C levels also have other conditions, such as high blood pressure, obesity, or diabetes, which significantly increases their risk of ASCVD and cardiovascular events。
LeqvioRNAi is an Rnai therapy targeting PCSK9 protein mRNA that is prescribed for injection as an adjunct to dietary and statin therapy for the treatment of adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia, to reduce LDL-C levels。Leqvio was initially approved by the US FDA in December 2021。The press release notes that it is the first small interfering RNA (siRNA) therapy capable of lowering LDL-C。
ORION-8Results from the open-label extension trial showed that treatment with Leqvio twice a year, in addition to statin therapy, sustainably reduced patients' LDL cholesterol after 6 years of treatment。Of these, 8 out of 10 patients reached the target LDL-C threshold, consistent with previously reported phase 3 data。Long-term safety data are consistent with previous results, confirming that Leqvio therapy has a well-established and favorable safety profile。
（信息来源：药明康德）
Bayer BRT-DA01 therapy in Parkinson's disease: Phase 1 clinical study meets primary endpoint
Bayer (Bayer) and its BlueRock Therapeutics (Bluerock Therapeutics) announced on August 29 that their stem cell-derived therapy bemdaneprocel (BRT-DA01) reached its primary endpoint in a phase 1 clinical trial for the treatment of Parkinson's disease。Detailed data were presented at the International Congress on Parkinson's Disease and Movement Disorders。Based on these results, a phase 2 clinical trial of the therapy is being planned, with patient enrollment expected to begin in the first half of 2024。
Parkinson's disease is the most common neurodegenerative movement disorder, affecting more than 10 million people worldwide。It is caused by damage to nerve cells in the brain, leading to decreased levels of dopamine in the brain, a neurotransmitter involved in processes such as memory or movement。The condition usually begins with tremors in one hand, and other symptoms include muscle stiffness, spasms, and dyskinesia (involuntary twisting movements of the face, arms, legs, or torso).。Dopamine substitutes are commonly used to reduce disease symptoms, such as levodopa, but their effects diminish as the disease progresses。By targeting the root cause of the disease, cell and gene therapy aims to move beyond a treatment model that alleviates symptoms。
BemdaneprocelIt's an ongoing cell therapy consisting of dopamine-producing neurons derived from pluripotent stem cells that can be surgically implanted into the brains of people with Parkinson's disease。When these cells are transplanted, they have the potential to rebuild damaged neural networks in the brains of patients with Parkinson's disease, thereby restoring motor and non-motor function。
The study met its primary goal of demonstrating that bemdaneprocel was safe and tolerated in all 12 subjects in the low - and high-dose groups, with no reported serious adverse events associated with the therapy within one year。Two serious adverse events unrelated to bemdaneprocel, including one surgically induced seizure and one case of COVID-19, resolved without sequelae。In addition, 18F-DOPA PET imaging scans showed evidence of cell survival and implantation in both the low - and high-dose groups。The 18F-DOPA PET imaging scan is a neuroradiological technique used to visualize and evaluate dopaminergic activity in Parkinson's disease。
Hauser Diary was used to classify patients. Patients in the "open" state indicated that their symptoms were well controlled.In the "off" state, symptoms worsen。Compared with baseline, participants in the high-dose group of the bemdaneprocel clinical trial spent 2 percent more time in the "switched on" status after one year.16 hours, and no movement disorders;The time in the "off" state is reduced by 1.91小时。Subjects in the low-dose group spent 0. 0 more time in the "on" state than at baseline.72 hours, and no movement disorders, the time in the "off" state decreased by 0.75小时。
In the high-dose group, the one-year efficacy of bemdaneprocel in the "discontinuation" state was scored using Part III of the Parkinson's Disease Rating Scale MDS-UPDRS, which was 13 points lower than baseline.0分的结果。In the low-dose group, results were 7 percent lower than baseline.6分。
（信息来源：药明康德）
Two Phase 3 trials meet primary endpoint!Abbvimab completes European and American regulatory applications for the treatment of ulcerative colitis
AbbVie has submitted a new indication application for Skyrizi (risankizumab) to the U.S. FDA and the European Medicines Agency (EMA) for the treatment of adults with moderate to severe ulcerative colitis (UC)。The application is based on data from two Phase 3 trials, INSPIRE and COMMAND, supporting risankizumab as induction and maintenance therapy, and analysis showed that the trial met the primary endpoint of clinical response (based on the adaptive Mayo score) and key secondary endpoints。
Ulcerative colitis is a chronic, idiopathic, immune-mediated inflammatory bowel disease (IBD) that causes persistent mucosal inflammation of varying degrees from the rectum to the more proximal colon。The signature signs and symptoms of ulcerative colitis include rectal bleeding, abdominal pain, bloody diarrhea, posttenesia (pressure), urgency to urinate, and fecal incontinence。The course of ulcerative colitis varies from patient to patient, and in some cases can cause complications (including cancer and death) or lead to the need for surgery。The severity of the symptoms and the unpredictability of the course of the disease place a heavy burden on patients and are often disabling。
RisankizumabIt is a humanized monoclonal antibody to the IgG1 subtype that selectively antagonizes IL-23 by binding to the p19 subunit of IL-23。IL-23 is a cytokine involved in inflammation and is thought to be involved in many chronic immune diseases。Skyrizi currently has three FDA-approved indications, including Crohn's disease, moderate-to-severe plaque psoriasis, and active psoriatic arthritis in adults。
分析显示，接受180mg、360mg risankizumab治疗的患者中，有显著更高比例在52周时达到临床缓解：分别为40%和38%，此数值在对照组中为25%（p<0.01）。接受180mg与360mg risankizumab治疗的患者中，分别有51%与48%达到内镜检查改善，而仅有32%对照组患者产生改善（p<0.001）。此外，接受180mg与360mg risankizumab治疗的患者中，分别有43%和42%的患者达到组织学内镜检查粘膜改善，显著高于对照组患者（23%，p<0.001）。此外，接受180mg与360 mg risankizumab治疗的患者中，亦有显著更高的比例在52周时达到无皮质类固醇的临床缓解（p<0.01）。
Safety results were consistent with the safety profile of risankizumab in other indications observed in previous studies, and no new safety risks were observed。
（信息来源：药明康德）
基石药业择捷美®A registered clinical study of first-line treatment for gastric/gastroesophageal junction adenocarcinoma met the primary endpoint of overall survival
8On October 29, Cstone Pharmaceutical, an innovative pharmaceutical company in Hong Kong, announced its potentially best-in-class tumor immunotherapy drug Zemet®The Phase III study (GEMSTONE-303) of Suglizumab injection in combination with first-line chemotherapy for inoperable locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma (GC/GEJ) with ≥5% PD-L1 expression met the primary endpoint of overall survival (OS)。研究显示，择捷美®Combined chemotherapy as first-line therapy can significantly prolong OS in patients with locally advanced or metastatic GC/GEJ, and the difference is statistically significant and clinically significant。It is important to note that the GEMSTONE-303 study has reached the pre-set double endpoints of progression-free survival (PFS) and OS, as well as key secondary endpoints, and detailed study data will be presented at an international academic conference in the near future。
In response, Dr. Jianxin Yang, Chief Executive Officer of Cstone Pharmaceutical, said, "We are very pleased to see Zemei®It has proved its outstanding efficacy and clinical value in the first-line treatment pattern of gastric cancer。此前，择捷美®It has been successful in the treatment of stage III and IV non-small cell lung cancer (NSCLC), esophageal cancer (ESCC), and relapsed refractory extratodal NK/T cell lymphoma (R/R ENKTL)。至此，择捷美®All registered clinical trials have been successfully concluded。We also plan to engage with the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) to explore global registration paths and strive to bring Zemet to market®This innovative treatment has brought gastric cancer patients around the world。”
It is understood that the NMPA is reviewing Zemei®Application for a new indication for the first-line treatment of advanced gastric cancer with combination chemotherapy, Zemei®It is expected to become the world's first PD-L1 monoclonal antibody approved in GC/GEJ indications。
达成OS和PFS双终点
择捷美®带来胃癌新治疗选择
Stomach cancer is one of the most common cancers in the world. According to GLOBOCAN 2020, there are more than 1 million new cases of stomach cancer worldwide in 2020, and 76 deaths.90,000 cases, the fifth most common cancer and the fourth leading cause of cancer death worldwide;China is one of the countries with the most serious gastric cancer burden in the world, with nearly half of the new cases and deaths of gastric cancer in the world every year。The incidence of gastric adenocarcinoma accounts for more than 90% of gastric malignant tumors, and the incidence of gastroesophageal junction adenocarcinoma is also on the rise in recent years。
For reaching the main study endpoint of OS this time, Zemei®GEMSTONE-303Professor Lin Shen, principal investigator of the study from Peking University Cancer Hospital, said: "Clinically, most patients with gastric adenocarcinoma are already in an advanced stage at the time of diagnosis and cannot be surgically removed, while patients with advanced or metastatic gastric cancer usually have a poor prognosis and unmet medical needs。Today, we are pleased to see positive OS results from the GEMSTONE-303 study。择捷美®Combination chemotherapy significantly prolongs PFS and OS in GC/GEJ patients and is safe and tolerable。我们相信未来择捷美®Could bring much anticipated new treatment options to this patient population。”
GEMSTONE-303It was a multicenter, randomized, placebo-controlled Phase III registered clinical trial to evaluate Zezimet®Efficacy and safety of combination chemotherapy as a first-line treatment for locally advanced or metastatic GC/GEJ with inoperable PD-L1 expression ≥5%。The primary endpoints of the study were investigator-assessed PFS and OS; secondary endpoints included PFS assessed by a blind independent central review committee, and investigator-assessed objective response rate and duration of response。Public information shows that in November 2022, the GEMSTONE-303 study reached the PFS primary study endpoint and showed a clear benefit trend in the OS interim analysis。Compared to a control group with placebo combined with chemotherapy, Zemet®Combination chemotherapy significantly improved PFS assessed by the investigators, and the difference was statistically significant and clinically significant。
Five registered clinical studies were successful
It is expected to be approved overseas in the first half of next year
Cornerstone Pharmaceutical 2023 semi-annual report shows that choose Jiemei®Has been successful in five registered clinical studies covering stage III NSCLC, Stage IV NSCLC, R/R ENKTL, GC/GEJ, and ESCC。
值得注意的是，择捷美®In a number of clinical studies in a number of different indications, it has shown efficacy beyond that of other PD-L1 monoclonal antibodies。It is the first PD-L1 monoclonal antibody in combination with chemotherapy to improve OS in patients with squamous and non-squamous stage IV NSCLC.It is the first PD-(L)1 monoclonal antibody in the world to significantly improve PFS in patients with stage III NSCLC who do not have disease progression after concurrent or sequential chemoradiotherapy.It is the first PD-L1 monoclonal antibody in the world to achieve positive results in GC/GEJ Phase III clinical study.It is expected to become the world's first approved tumor immunotherapy drug for R/R ENKTL and the world's first PD-L1 monoclonal antibody for the treatment of locally advanced, relapsed or metastatic ESCC that cannot be resected surgically。Data from the above studies have been published in top international journals such as The Lancet Oncology and the Journal of Clinical Oncology。
In the domestic market, the NMPA has approved Zemei®For two indications in the field of stage III and stage IV NSCLC。In addition to GC/GEJ, marketing applications for new indications in the R/R ENKTL and ESCC fields have also been accepted by NMPA and are currently under review。
In the overseas market, the marketing authorization application for the first-line treatment of stage IV NSCLC of Suglizumab was accepted in the EU and the UK in February this year and December last year, and the progress is in the first echelon of domestic PD-(L)1 antibodies to the sea。In July this year, Cstone has received a clinical trial verification notice issued by the EMA, and the road to the overseas listing of Suglizumab has made significant progress, which is expected to achieve overseas approval in the first half of 2024。
（信息来源：生物探索）
Hengrui medicine dexmedetomidine hydrochloride nasal spray for children was approved
8On October 24, the latest announcement on NMPA's official website, Hengrui Pharmaceutical's 2.The application for dexmedetomidine hydrochloride nasal spray, a class 2 new drug, has been approved。According to the CDE priority review announcement, the approved indications for this product are: preoperative sedation for children (such as general anesthesia for children).。Previously, the product has been approved by the NMPA for pre-operative sedation/anti-anxiety use in adults。
Dexmedetomidine hydrochloride is a relatively selective α2-adrenoceptor agonist, originally developed by Oricon Pharma and Abbott and first approved in the United States in 1999 (Precedex).。According to the earlier press release of Hengrui Medicine, dexmedetomidine has the characteristics of strong, short-acting, high selectivity, short action time, easy to adjust the sedation level, and can quickly adjust the sedation score of the expected target。The advantages of this product are that it maintains wakeability while sedating, rarely induces clinically significant respiratory depression, and has minimal hemodynamic effects, making it a good choice for sedation before, during, or other procedures in non-intubated patients。
Previously, the dexmedetomidine hydrochloride injection developed by Hengrui Medicine was approved for market in China in 2009 for the sedation of tracheal intubation and mechanical ventilation in patients undergoing surgery under general anesthesia。To facilitate clinical use, the company also developed dexmedetomidine hydrochloride sodium chloride injection, which was approved in China in 2021, for sedation during intubation and mechanical ventilation in intensive care patients, and for pre-operative and/or intraoperative sedation in non-intubated patients, as well as other procedures。
In addition, the company has developed a nasal spray of dexmedetomidine hydrochloride, which was approved in China in March 2023 for pre-operative sedation/anti-anxiety in adults。Spray is a kind of drug delivery system in which the drug enters the deep respiratory tract or the mucous membrane of the lumen after being administered by a special drug delivery device, and then exerts systemic or local effects。This product is mainly absorbed through the nasal mucosa and has the advantages of easy to use and rapid effect。
The NMPA approved dexmedetomidine hydrochloride nasal spray for children。Previously, the application was included in the priority review by the CDE for "new varieties, dosage forms and specifications of children's drugs that meet the physiological characteristics of children" and are intended to be used for preoperative sedation of children (such as children's general anesthesia).。
In recent years, with the increase of the amount of anesthesia, the prevention and treatment of preoperative anxiety has been paid more and more attention。Before anesthesia, children are separated from their parents, fear of unfamiliar environment and anesthesia and other factors can cause tension and anxiety. Pre-operative tension and anxiety not only affect the normal operation of anesthesia, but also may affect postoperative recovery。Good preoperative sedation can effectively reduce the tension and anxiety of children and reduce the pain of separation from parents。
The new indication of dexmedetomidine hydrochloride nasal spray of Hengrui Medicine was approved, which is expected to bring better anesthesia treatment options for more children。
（信息来源：医药观澜）
Hengrui JAK1 inhibitor Amexitinib new indication for listing
8On October 24, the CDE official website showed that the marketing application for the new indication of Hengrui JAK1 inhibitor Amexitinib tablet (SHR0302) was accepted。According to the progress of clinical trials, it is speculated that the indication for listing in this application is to treat adult patients with active ankylosing spondylitis。
SHR0302It is a highly selective JAK1 inhibitor independently developed by Hengrui Medicine, a national Class 1 new drug, and an oral small molecule innovative drug independently developed in China with a class of intellectual property rights, which can play a biological effect of anti-inflammatory and immune suppression by inhibiting JAK1 signal transduction。
SHR0302At present, clinical studies have been carried out in various fields including rheumatoid arthritis, ulcerative colitis, atopic dermatitis, alopecia areata, psoriatic arthritis and so on。2021年1月，SHR0302 tablets are granted breakthrough therapy status by the National Drug Administration，For the treatment of moderate and severe atopic dermatitis in adults and adolescents over 12 years of age，At present, the clinical results of Ill stage have reached the common primary endpoint and secondary endpoint，Hengrui submitted a marketing application for this indication in June 2023。
2018年1月，Hengrui Pharma has entered into a cooperation agreement with Arcutis Inc. for SHR0302，按照协议的内容，Arcutis received exclusive clinical development, registration and marketing rights for the SHR0302 program in the United States, the European Union and Japan，The licensed dosage forms of SHR0302 developed and marketed are topical preparations for the treatment of skin disorders;Hengrui Medicine can get a total of 2.A $2.3 billion down payment and milestone payments, plus sales commissions。
（信息来源：医药魔方）
The world's only for the treatment of IgA nephropathy drugs!Genting Xinyao Fu Kang®The application for marketing authorization was officially accepted by the Drug Administration of Macao, China
Genting Xinyao, a biopharmaceutical company focused on the development, manufacturing and commercialization of innovative drugs and vaccines, announced on August 25 that the Drug Administration of the Macao Special Administrative Region of China has officially accepted Nefukang®A marketing Authorization application (NDA) for the treatment of adult patients with IgA nephropathy is expected to be approved within 2023。China's National Medical Products Administration and Singapore's Health Sciences Authority have accepted Nefukang in November 2022 and April 2023, respectively®NDA, the approval of the listing application in Macau marks that Genting Xinyao is expected to provide more Asian patients with IgA nephropathy with the first treatment for this disease。
耐赋康®It has been successively approved for marketing in the United States and the European Union, and the United States FDA has accepted the submission of the partner Calliditas Therapeutics®The fully approved Supplemental New Drug Marketing Application (sNDA) for the treatment of IgA nephropathy has been granted priority review and a review decision is expected by December 20, 2023。此外，耐赋康®The new drug marketing authorization application has also been granted priority review status by the China National Medical Products Administration and is expected to be approved in the second half of this year。耐赋康®It was also included in the breakthrough Therapeutics program as the first non-tumor drug in China, underscoring the importance of this first-of-its-kind drug for the approximately 5 million IgA nephropathy patients in China。From April 2023, Nefu Kang®It has been applied to clinical use in Hainan Hospital, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine through the early access project。
关于耐赋康®（Nefecon®）
耐赋康®（Nefecon®It is an oral targeted budesonide delayed release capsule. As the world's only therapeutic drug for IgA nephropathy, it is a mucosal immunomodulator targeting the intestine, which can reduce the decline of renal function by 50% and delay the time of disease progression to dialysis or kidney transplantation for more than 10 years。Budesonide is a kind of glucocorticoid with strong glucocorticoid activity and weak salt corticoid activity. The first pass metabolism degree reaches 90% and has good safety。耐赋康®专为IgA肾病患者研制，Delayed release capsule contains budesonide 4mg，通过特殊的制作工艺，Targeted release of budesonide to mucosal B cells at the end of the ileum (including Pyle aggregate lymph nodes)，胶囊溶解后，The three-layer coated pellets consistently and steadily release budesonide，高浓度覆盖整个靶区域，Thus, the production of IgA1 antibody (Gd-IgA1) that induces galactose deficiency in IgA nephropathy is reduced，Then intervene the upstream stage of pathogenesis，It has the effect of treating IgA nephropathy。In June 2019, Genting Xinyao entered into an exclusive licensing agreement with Calliditas to develop and commercialize Nefukang in the Greater China region and Singapore®的权利。The agreement was extended in March 2022 to include South Korea in the scope of Genting Xinyao's licensing。
（信息来源：药智新闻）
Kingax/Ingapai PARP inhibitors were declared for the first line maintenance treatment of ovarian cancer in the whole population
8月25日，君实生物发布一则公告，Announced that its joint investment with Yingpai Pharmaceutical Junpai Yingshi Pharmaceutical received the State Drug Administration approved and issued the "Acceptance Notice"，New Drug Application for polyadenosine diphosphoribose polymerase (PARP) inhibitor senaparib Accepted (CXHS2300073)，For the maintenance of patients with stage III-IV epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer who have achieved complete or partial response to first-line platinum-containing chemotherapy。
SenaparibIt is a PARP inhibitor, which has obtained the project support of the "13th Five-Year Plan" national major New drug creation special project and successfully completed the acceptance。In August 2022, senaparib and Temozolomide, a fixed-dose combination capsule for the treatment of adult patients with small cell lung cancer, received orphan drug designation from the U.S. Food and Drug Administration。
This new drug marketing application is mainly based on FLAMES research (NCT04169997).，The study was a randomized, double-blind, placebo-controlled, multicenter Phase III clinical study，To evaluate the efficacy and safety of senaparib monotherapy maintenance in patients with FIGO stage III-IV ovarian cancer after achieving complete response (CR) or partial response (PR) with first-line platinum-containing chemotherapy。
FLAMESThe interim analysis of the study showed that senaparib significantly extended progression-free survival (PFS) in patients with advanced ovarian cancer, regardless of their breast cancer susceptibility gene (BRCA) expression。
Ovarian cancer is one of the most common fatal malignancies of the female reproductive tract。According to statistics, the annual number of new cases of ovarian cancer in the world is about 310,000, and the annual number of deaths is about 210,000。Because the early symptoms of ovarian cancer are insidious and non-specific, about 80% of patients are diagnosed with advanced stage, and the 5-year survival rate is only 40%。Although ovarian cancer can go into remission after initial platinum-containing chemotherapy, most patients inevitably face recurrence。In recent years, PARP inhibitors are changing the treatment landscape of ovarian cancer, and their maintenance therapy can extend the duration of remission after first-line platinum-containing chemotherapy and delay recurrence。
According to the Pharmaceutical Rubik's Cube database, there are currently four PARP inhibitors approved for sale in China, namely Astrazeneca/Merck's Orapalil, GSK/ Re Ding's Nilapalil, Henri/Hausen's Fluzopalil and Beigene's Paripalil。However, of these four products, only nilapalil is approved for population-wide first-line maintenance for advanced ovarian cancer。
Recently, Hengrui announced that the marketing authorization application for the new indication of fluzopalil has been accepted by the State Food and Drug Administration, and it is intended to be used for maintenance treatment of patients with advanced epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer after achieving complete or partial remission in first-line platinum-containing chemotherapy。
（信息来源：医药魔方）
The European Union approved Roche Evrysdi for the treatment of infants under two months of age with spinal muscular atrophy
8月29日，罗氏(RHHBY.US)在一份声明中表示，The European Commission has approved the extension of its Evrysdi or risdiplam treatment to infants under two months of age diagnosed with spinal muscular atrophy，This means that Evrysdi is now available to treat spinal muscular atrophy patients of all ages in the EU，包括出生后的婴儿。
据了解，The Swiss pharmaceutical company said on Tuesday，The approval is based on interim data from an ongoing RAINBOWFISH trial，该试验显示，Most infants treated with Evrysdi were able to stand and walk within the typical time range of healthy infants after 12 months of treatment。
Evrysdi is the only non-invasive SMA treatment approved in 100 countries and has treated more than 11,000 patients worldwide, according to Roche。
It is worth mentioning that the company is currently studying Evrysdi in combination with an anti-myostatin molecule that targets muscle growth for the treatment of SMA in the Ph II/III trial MANATEE。
（信息来源：智通财经）
Bristol-myers Squibb announces FDA approval of Reblozyl®As a first-line treatment for anemia in low-risk adult patients with myelodysplastic syndrome
Bristol-myers Squibb announced on August 29 that the US FDA has approved Reblozyl®(luspatercept-aamt)For the treatment of anemia without the use of a previous erythropoietic stimulator for adult patients (who have not received ESA) with very low - to moderate-risk myelodysplastic syndromes (MDS) who may require regular red blood cell (RBC) transfusions。The expanded indication for this first-line treatment is based on interim results from the pivotal Phase 3 COMMANDS trial，Among them, Reblozyl is compared to Alfa Epotin (an ESA)，No matter what the status of the cycloblast is，It showed excellent efficacy in the simultaneous increase of RBC transfusion independence (RBC-TI) and hemoglobin (Hb)。These results highlight Reblozyl's ability to address chronic anemia in a wider range of patients earlier in the course of treatment。
Lead investigator Guillermo Garcia-Manero, MD, said: "For low-risk MDS patients, current standard therapies, including ESA, have limited effectiveness in controlling anemia, with only one in three patients responding within 6-18 months。Director of myelodysplastic syndromes at the University of Texas MD Anderson Cancer Center。"The results of the COMMANDS study showed that nearly twice as many patients treated with Reblozyl achieved at least 12 weeks of blood transfusion dependence with a simultaneous increase in hemoglobin compared to alfa epotin。Today's approval is an important step forward for low-risk MDS patients。”
In the Phase 3 COMMANDS trial, results showed 58 of the patients treated with Reblozyl.5%(n=86) compared with 31 in patients treated with epoetin alfa.2%(n=48) achieved an average Hb increase of at least 1 in the 24 weeks prior to the primary endpoint of RBC-TI for at least 12 weeks.5 g/dL (p<0.0001)。最常见（>10%）的不良反应是腹泻、疲劳、高血压、外周水肿、恶心和呼吸困难。
Wendy Short-Bartie, senior vice President and general manager, said: "Today's expanded approval of Reblozyl marks an important milestone in our commitment to patients with anemic MDS，By providing lasting and more effective treatment options，And more convenient and less frequent dosing，”美国血液学和细胞治疗，百时美施贵宝。"We remain committed to addressing difficult-to-treat diseases that place a heavy burden on patients and look forward to providing this important option early in the treatment process.。”
"Most MDS patients have chronic anemia and require red blood cell transfusions," says Tracey Iraca, executive director of the MDS Foundation。"The approval of Reblozyl for the first-line treatment of anemia in low-risk MDS patients represents a critical step towards enabling more patients to have independent blood transfusions.。”
COMMANDSThe results of the study were featured in June as part of the news program of the Annual meeting of the American Society of Clinical Oncology (ASCO) and the plenary session of the General Assembly of the European Society of Hematology (EHA), and simultaneously published in The Lancet。As of November 2021, Reblozyl is being developed and commercialized through a global collaboration with Merck。
COMMANDSCOMMANDS(NCT03682536) is a phase 3, open-label, randomized study evaluating Reblozyl versus Epoetin alfa for the treatment of very low, low, or moderate risk (IPSS-R) -induced anemia
Efficacy and safety Myelodysplastic syndrome (MDS) occurs in patients who rely on red blood cell (RBC) transfusion and are not treated with erythropoietic stimulants (ESAs)。
The primary endpoint assessed in this study was red blood cell transfusion independence (RBC-TI) for 12 weeks with an increase in mean hemoglobin (Hb) of ≥1.5 g/dL。Key secondary endpoints included red blood cell response (HI-E) for at least 8 weeks between weeks 1 and 24 of the study, RBC-TI≥12 weeks, and RBC-TI persistence for 24 weeks。Eligible patients are those ≥18 years of age who have low-risk MDS and require blood transfusion。Patients were randomized 1:1 to receive subcutaneous injections of Rebrozyl (initial dose 1.0 mg/kg titrated to 1.75 mg/kg) once every 3 weeks or alfa epotin (starting dose 450IU/kg titrated to 1050 IU/kg) once a week for ≥24 weeks。大多数研究参与者(>90%)不在美国，此类患者的对照组使用的是非美国许可的阿法依泊汀产品。
(Source: biospace)
Merck's cancer drug Keytruda received EU approval for the combination treatment of stomach cancer
默沙东(MRK.US) announced on August 29 that the European Commission approved its anti-PD-1 drug Keytruda as part of a combination regimen as a first-line option for the treatment of gastric or gastroesophageal junction (GEJ) adenocarcinoma。
Therefore, the immunotherapy Keytruda will be used in the region for human epidermal growth factor receptor 2(HER2) positive gastric cancer or GEJ adenocarcinoma for chemotherapy and the anti-cancer drug trastuzumab。
The decision, which applies to EU member states as well as Iceland, Liechtenstein, Norway and Northern Ireland, was given a positive opinion in July by a panel of experts from the EU's drugs regulator, the European Medicines Agency (EMA)。
The approval was supported by data from the Phase 3 KEYNOTE-811 trial of Merxadon, in which patients with first-line Keytruda+ trastuzumab and chemotherapy showed significant improvements in progression-free survival (PFS) compared to patients with trastuzumab + chemotherapy。
However, the 732-patient trial did not meet the other primary endpoint of overall survival (OS), but there was a trend toward improvement。Overall survival analysis data is currently in progress。
（信息来源：智通财经）
第一三共优赫得®It is the first HER2-targeted therapy approved in Japan for HER2-mutated metastatic non-small cell lung cancer
8On 23 October, Daiichi Sankyo announced that Yohod®(Tetrastuzumab for injection) was approved in Japan for the treatment of adult patients with unresectable advanced or recurrent non-small cell lung cancer (NSCLC) with HER2 (ERBB2) mutations whose disease has progressed after chemotherapy。
Lung cancer is the second most common cancer in Japan, with more than 138,000 cases diagnosed in 2020。在日本，只有18.Two percent of patients with metastatic NSCLC survive more than three years after diagnosis, resulting in a particularly poor prognosis for this subset of patients。
The Japanese Ministry of Health, Labour and Welfare (MHLW) approved the project based on Youhede®Results of the Phase II clinical study DESTINY-Lung02, presented at the 2022 Annual meeting of the European Society of Medical Oncology (ESMO)。优赫得®It previously received MHLW "orphan drug designation" for this tumor, which also supports Youhde®获得优先审评资格。
As evaluated by a blinded Independent Center Review (BICR), a preset interim analysis of previously treated patients with HER2-mutated NSCLC in DESTINY-Lung02 showed that Youhde was positive®（5.The proven objective response rate (ORR) of 4mg/kg in patients with unresectable advanced or recurrent non-small cell lung cancer with HER2 (ERBB2) mutations who had previously received chemotherapy was 53.8% (n=52;95% confidence interval [CI] : 39.5～67.8）。
In DESTINY Lung02, Yohod®The safety profile was consistent with previous clinical studies and no new safety concerns were identified。接受优赫得®（5.93 patients treated with 4mg/kg (92.1%) treatment-related adverse events (aes) occurred。The most common treatment-related AE was nausea (59.4%) and decreased neutrophil count (33.7%）、贫血（28.7%）、食欲下降（28.7%）、疲乏（25.7%）、便秘（24.8%), decreased white blood cell count (23.8%）和呕吐（22.8%）。在中期分析中，2.Seven percent of Japanese patients are receiving Eucat®(5.4mg/kg)Interstitial lung disease (ILD) developed during treatment.。
优赫得®The efficacy and safety of neoadjuvant therapy, adjuvant therapy, or first-line metastatic therapy in patients with advanced unresectable or relapsed NSCLC with HER2 (ERBB2) mutations have not been established。优赫得®Only for NSCLC patients with HER2 (ERBB2) mutations confirmed by an approved test。
关于优赫得®
优赫得®(Dextrastuzumab for injection;fam-trastuzumabderuxtecan-nxki in the United States is a HER2-targeted antibody-coupling drug (ADC).。优赫得®Using Daiichi Sankyo's unique DXd-ADC technology, it is the leading ADC product in Daiichi Sankyo's oncology portfolio and the most advanced project in Astrazeneca's ADC Science platform。Yohde consists of a HER2 monoclonal antibody linked to a topoisomerase I inhibitor payload (an ehitecan derivative) via a stable cleavable tetrapeptide linker。
Based on the findings of the DESTINY-Breast03 study, Yohede®（5.4mg/kg) has been approved in more than 50 countries，For the treatment of adults with unresectable or metastatic HER2-positive breast cancer who have previously received (one or more) anti-HER2 regiments during or during neoadjuvant therapy or adjuvant therapy and who have experienced disease recurrence during treatment or within 6 months after completion of treatment。
Based on the findings of the DESTINY-Breast04 study, Yohede®（5.4mg/kg) has been approved in more than 40 countries，It is used to treat patients who have previously received a systemic therapy during the metastatic phase，Or adult patients with unresectable or metastatic HER2 low expression (immunohistochemical [IHC]1+ or IHC2+/ in situ hybridization [ISH]-) breast cancer who experienced disease recurrence during adjuvant chemotherapy or within 6 months after completing adjuvant chemotherapy。
Based on the results of the DESTINY-Lung02 study, Yohed®（5.4mg/kg) has been approved in Israel and Japan，且在美国获得加速批准，For the treatment of adults with unresectable or metastatic NSCLC whose tumors have HER2 (ERBB2) activating mutations detected by a locally or regionally approved test and who have previously received one systemic therapy。When the clinical benefit in confirmatory studies is validated and established, full approval of this indication in the United States will be supported。
Based on the results obtained from the DESTINY-Gastric01 study and/or the DESTINY-Gastric02 study, Youhede®（6.4mg/kg is approved in more than 30 countries for the treatment of locally advanced or metastatic HER2-positive gastric or esophagogastric junction (GEJ) adenocarcinoma in adults who have previously received trastuzumab based therapy。
（信息来源：药智新闻）
亳州市场8月31日快讯
太子参价格：Recently, the market continues to produce new listings, the market to increase the amount of goods, the demand is general, the market correction。At present, Anhui unified goods price is about 55 yuan /kg in the market, Guizhou unified goods price is about 60 yuan /kg, small unified goods price is about 50 yuan /kg, and the selection of small particles is different from the price of 80-120 yuan /kg。
五味子价格：Origin began to produce new harvest, small batch of new goods listed, the market supply of general purchase and sales, the market stabilized。At present, the price of unified goods on the market is 64-65 yuan /kg, and the price of high-quality goods is 68-70 yuan /kg。
天南星价格：There are business consulting purchase and sales, small batch purchase and sales of goods, the market is stable。At present, the market Arilium unified goods 45-50 yuan /kg, the selection of particle size and quality of different prices 60-70 yuan /kg。
乌梢蛇价格：The volume of the market has increased, the current demand is general, there are inquiries to buy and sell, the market remains stable。At present, the market price of Wuzao snake in Sichuan unified goods is 630-650 yuan /kg。
首乌藤价格：There are merchants to buy, small batch to move around, the market is stable。At present, the price of Wuteng Sichuan unified goods in the market is 15-16 yuan /kg, and the selection of goods is 18-20 yuan /kg。
水菖蒲价格：Recently, the quantity of goods from the origin is not much, the market demand has increased, and the market is stable。Now the market water calamus large unified goods price 20-24 yuan /kg, small unified goods 16-17 yuan /kg。
桂枝价格：The market supply is sufficient, the supply volume is moving, and the market is stable。At present, the market price of small pieces of cassia branch is 12-13 yuan /kg, small pieces 8-9/kg, and large pieces 5-6 yuan /kg。
石菖蒲价格：The overall circulation of the market is OK, and the market fluctuates slightly。At present, Anhui unified goods asking price 75-80 yuan /kg, Hunan and Fujian region unified goods asking price 73-75 yuan /kg。
鸡内金价格：The supply of chicken gold in the market is generally moving, and the market is stable。At present, the market price of chicken inner gold unified goods is 10-11 yuan /kg, and the optional price is 12-13 yuan /kg。
(Information source: Kangmei Chinese Medicine Network)
安国市场8月31日快讯
昆布，The previous market decline, the recent impact of nuclear water pollution in Japan, concern about the increase of businesses, the supply of goods to go smoothly, the market has risen, and the market is now the price of laminai full inspection beverage pieces at 30 yuan。
海藻，Recently, affected by Japan's nuclear water sewage, there are more businesses concerned, and the supply volume is sold smoothly, and the market is steadily rising, and the market price of seaweed leaves is 15 yuan, and the price of small-leaf goods is 20 yuan。
辛夷花，At present, the market is in the off-season, the recent supply of goods is generally sold, the market is running in the firm, the price of Xinyi florets is 60 yuan, the price of large flowers is between 65-66 yuan, and the price of handless goods is between 73-74 yuan。
佛手，At present, the new production continues, there are businesses concerned, the supply of goods to go smoothly, the holder shouted the price is strong, the market now Guangxi Buddha hand price in 52 yuan, Sichuan goods price in 53 yuan, Guangdong goods price in 65 yuan。
伸筋草，At present, the processing of production areas continues, the market and production areas are sufficient for supply, the market and the previous period remain stable, and the current market price of extended grass is 7.5元。
水栀子，At present, it is green, business attention is general, the market and the previous period to maintain stability, the market price of good water gardenia color is between 27-28 yuan, the pharmaceutical factory price is about 24 yuan。
五味子，Recently affected by the new production, the cargo holder is willing to ship stronger, the market has declined significantly, and the market price of schisandra schisandra is about 64 yuan。
鳖甲，In the near future, there are more businesses to pay attention to, the batch of goods is sold smoothly, the market is running strongly, and the market price of turtle shells is between 130-135 yuan。
淡豆豉，The market sales volume is relatively small, the supply of goods is generally sold, the market has remained stable with the previous period, and the general price of light soy beans in the market is between 12-15 yuan, and the price of full inspection goods is 17 yuan。
肉豆蔻，The supply is sufficient, the recent business attention is general, the normal purchase and sale of goods, the market and the previous period remained stable, the current market nutmeg stock price between 58-60 yuan, the special jade fruit price between 67-69 yuan。
熟地黄，Affected by the downward adjustment of Rehmannia market, the processing cost is reduced, the recent normal purchase and sale of goods, the market performance is weak, and the market price of cooked Rehmannia small pieces is 26 yuan, and the price of large unified goods is 28 yuan。
乌药，The supply of goods is sufficient, the recent sale is general, the market and the previous period remain stable, and the current market price of black medicine is 17 yuan, and the selection price is 25 yuan。
(Information source: Chinese Herbal Medicine World)
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