Evive Biotech

在美国药品监管实践中，PDUFA(处方药用户费用法案，Prescription Drug User Fee Act)日期是指FDA必须对新药申请或生物制品许可申请，做出回应日期的通俗名称。制药公司通常在提交新药申请时支付用户费，而FDA则在达到PDUFA日期前作出是否批准新药上市的决定，其有助于提高审批效率，加速新药上市，从而更快地使患者获得新的治疗选择。但并非所有的监管决定，都能按照PDUFA日期准时完成。012023年，7款新药错过PDUFA日期2023年，CDER批准了55款新药，但错过了6个PDUFA日期。CBER错过了1个。这一年里，FDA在遵守PDUFA日期方面的表现，大大违背与他们此前的KPI表现。7个PDUFA日期的延时，是FDA在过去12年里面的最差表现。CDER在PDUFA日期到期后批准了6种新药，占CDER 2023年批准的55种新分子实体和新型生物制剂的11%。2023年，CDER在PDUFA日期上的误时案例超过了过去11年的总和（图1）。在2012到2022年的11年间，CDER只有在2015年中错过了一个以上（2个）的PDUFA日期，其中有5年CDER保持了“零”的成绩。图1 CDERZAI 2012-2023年间按时和延误审批项目的数量和比例走势图图片来源：Pink SheetPDUFA的延时也许对于一般性的药物影响不大，但对那些潜在的重磅炸弹药物来说就真称得上“一寸光阴一寸金”了。我们可以做一个粗略的计算：如果一款药物上市后能达到重磅炸弹的地位，就以最低标准10亿美元来计算，每天的销售额就是274万美元。也就是说，FDA每耽搁一天，重磅炸弹药物的制药商的损失至少是274万美元，一周1918万美元，一个月8333万美元。这还是针对羽量级重磅炸弹，如果是Wegovy这样体量的重磅炸弹（2023年全年销售量数据尚未出炉，预计在131亿美元左右[[]Malone,E.Top 10 Best-Selling Drugs Of Q3 2023:Ozempic Challenges Humira As Keytruda Extends Leadership.Scrip.20.12.2023.]），延误一天等于3589万美元的损失。以上粗略的计算也解释了为什么有制药公司舍得花费价值在1亿美元左右的优先评审券（PRV，Priority Review Voucher）来将他们的资产审批时间缩短4个月。相对而言，CBER在遵守PDUFA日期这项KPI上表现尚可。只有Sarepta Therapeutics的杜氏肌营养不良症基因疗法Elevidys的审批被延误。CBER去年总共批准了17种新生物制剂，创下历史新高。022023年PDUFA日期延误分析COVID-19造成的限制，是2023年PDUFA延时最主要的原因。2023年批准的三种新型药物原本属于2022年的PDUFA日期，但因为Covid-19被推迟到了2023年审批（也被统计入2023年PDUFA延时）。Covid-19大流行恰逢中国制药公司寻求进入美国肿瘤市场的浪潮，但疫情和中国的防控政策导致了FDA的检查无法按时进行。Evive Biotech/Acrotech Biopharma LLC的Ryzneuta(efbemalenograstim alfa-vuxw)是一种长效粒细胞集落刺激因子融合蛋白，用于治疗化疗引起的中性粒细胞减少症，其PDUFA时间是2022年3月30日，但直到2023年11月16日才获得批准，因为Evive的北京原料药生产场地到2023年6月才能接受检查。同样，对无锡药明生物原料药和药品生产基地的检查也导致了Amicus Therapeutics,Inc.的Pombiliti（cipaglucosidase alfa-atga）的审批延迟。Pombiliti是一种针对罕见疾病庞贝病的酶替代疗法。君实生物和Coherus BioSciences,Inc.d的Loqtorzi（toripalimab-tpzi）是一款抗PD-1单克隆抗体，PDUFA日期为2022年12月23日，同样因为疫情控制而无法按时进行，最终于2023年10月27日获批，推迟了10个月的时间。另一款PD-1抑制剂是tislelizumab，目前仍在等待FDA的监管决定，距治疗食管鳞状细胞癌的初设PDUFA日期（2022年7月12日）已过去了17个多月。康方生物和中国生物制药的PD-1抑制剂penpulimab错过了2022年1月的三线NPC的PDUFA审批日期。FDA于2023年10月17日批准了UCB的Bimzelx(bimekizumab-bkzx)用于治疗斑块状银屑病，但此时已经距离其2020年7月15日BLA申请提交过去了三年零三个月，其中两次未能遵循PDUFA日期规定审批。CBER的PDUFA延期案例的原因较为清晰。CBER 2023年PDUFA延期孤例的“事主”是Sarepta的杜氏肌营养不良症基因疗法Elevidys。这款药物的上市本身就充满了争议。CDER在2016年加速批准Sarepta的外显子跳跃Exondys 51(eteplirsen)时，就已经制造出了FDA最具争议的事件之一。2023年，Sarepta再次为FDA奉上一份烫手山芋，只不过这次换成了CBER来决定Elevidys这款基因疗法的命运。CBER最初的反应是拒绝审查这份申请，但被CBER主任Peter Marks压下。由于对Elevidys替代终点的有效性和临床数据的分歧，CBER没有能够在Elevidys的2023年5月29日PDUFA日期做出监管决定。最终FDA进行了专家咨询会议进行投票表决，Elevidys在6月22日获得了批准。表1 FDA 2023年PDUFA日期延期一览表数据来源：FDA官网注：本文中延期的案例，针对的是PDUFA时间延期，但在2023年获批的情况。并非是2023年PDUFA没有按期审评的情况。1.Malone,E.Top 10 Best-Selling Drugs Of Q3 2023:Ozempic Challenges Humira As Keytruda Extends Leadership.Scrip.20.12.2023.2.Yan,D.Closed-Loop Inspections?Strict COVID Zero Policy Delays US FDA’s China Field Trips.Pink Sheet.26.05.2023.3.Sutter,S.Sarepta's Eteplirsen Approved After Contentious Internal FDA Debate.Pink Sheet.16.09.2016.声明：本内容仅用作医药行业信息传播，为作者独立观点，不代表药智网立场。如需转载，请务必注明文章作者和来源。对本文有异议或投诉，请联系maxuelian@yaozh.com。责任编辑 | 八角转载开白 | 马老师 18996384680（同微信）商务合作 |  张武龙 13368443108（同微信） 阅读原文，是受欢迎的文章哦

The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has given a thumbs up to Bristol Myers Squibb's Abecma and a thumbs down to Apellis' geographic atrophy drug Syfovre. Shortly after Europe’s Committee for Medicinal Products for Human Use (CHMP) recommended refusal of a marketing authorization for Apellis’ geographic atrophy (GA) drug Syfovre, the company said it will appeal the guidance. On the positive side of the ledger, the European Medicines Agency committee recommended marketing authorizations for four products, including a label expansion for Bristol Myers Squibb's multiple myeloma CAR-T Abecma. The thumbs down for Apellis' groundbreaking drug—which became the first treatment for GA upon its approval by the FDA in February of last year—was not a surprise. Last month, Apellis revealed that a panel of experts voted down the treatment after an “oral explanation meeting,” triggering a 17% slide in the company’s share price. Apellis' drug stumbled soon after its U.S. launch because of reports of vascular retinitis. The CHMP determined that the benefits of using Syfovre don't outweigh the risks. “Although the studies showed that Syfovre slowed the growth of geographic atrophy lesions, this did not lead to clinically meaningful benefits for patients,” the CHMP concluded. “It was noted that benefits of a treatment should impact patients’ everyday functioning, and this was not demonstrated in the studies.” For its part, the Massachusetts-based company pointed to results from two phase 3 trials which showed that the treatment reduced GA lesion growth, with treatment benefits accumulating over time.  “We are very disappointed in this outcome on behalf of the millions of Europeans with GA who currently have no treatment options for this irreversible form of blindness,” Jeffrey Eisele, Ph.D., Apellis’ chief development officer, said in a statement. “We plan to promptly initiate the re-examination of our application and address CHMP questions.” BMS scores with Abecma Meanwhile, the CHMP’s positive opinion on BMS’s Abecma is the first in earlier lines of treatment for a CAR-T cell therapy for multiple myeloma, according to the drugmaker.  CHMP specifically recommended the drug for patients who've tried two prior therapies, as opposed to the drug's initial EU nod in the fourth line of treatment. Samit Hirawat, M.D., BMS’s chief medical officer, called the endorsement an “important milestone.” “(It) moves us closer to offering a first-in-class, personalized therapy to patients in Europe battling this incurable disease after exhausting prior treatment options with the three standards of care.” Also gaining recommendations for label extensions were Apellis and Sobi's PNH drug Aspaveli, Pfizer's pneumococcal vaccine Prevnar 20 and Eli Lilly's thyroid cancer drug Retsevmo.  CHMP gives thumbs up to 3 products The CHMP recommended a marketing authorization for Allecra’s Exblifep (cefepime/enmetazobactam) for urinary tract infections accompanied by hospital-acquired pneumonia and for the treatment of patients with bacteria in the bloodstream. The antibiotic combination treatment also is under review by the FDA. Also getting a positive recommendation from the committee was Evive Biotech and Acrotech Biopharma’s Ryzneuta (efbemalenograstim alfa) for neutropenia and febrile neutropenia caused by chemotherapy. The FDA signed off on the leukocyte growth factor two months ago. The CHMP also said yes to Neuraxpharm’s schizophrenia medicine Niapelf (paliperidone), which is the generic version of Johnson & Johnson’s Invega Sustenna, which was approved in the U.S. in 2009 and in Europe as Xeplion in 2011. CHMP recommends rejection of Nezglyal Minoryx Therapeutics’ Nezglyal (leriglitazone) got a negative recommendation from the committee. The drug is for the treatment of the genetic condition cerebral adrenoleukodystrophy, which damages the brain and spinal cord. The Spanish company gained FDA fast-track designation for the treatment in 2020.

CAMBRIDGE, Mass., Dec. 10, 2023 /PRNewswire/ -- Nona Biosciences, a global pioneer of technology innovation and antibody discovery and development solutions, and Evive Biotech, a global biopharmaceutical company devoted to developing a portfolio of novel biological therapies for patients worldwide, today announced a collaboration agreement on antibody discovery based on the Harbour Mice® antibody technology platform of Nona Biosciences. The collaboration brings together professional advantages of Nona Biosciences and Evive Biotech, aiming to accelerate the process of antibody discovery and drug development to benefit patients faster. Harbour Mice® is a proprietary antibody technology platform that utilizes the transgenic mouse to generate fully human monoclonal antibodies in both a traditional two heavy and two light chain (H2L2) format and a heavy chain only (HCAb) format. This platform holds significant potential for the development of therapeutic antibodies and the acceleration of drug discovery and development. "Nona Biosciences is committed to bringing antibody discovery and research solutions to our partners better and faster," said Jingsong Wang, MD, PhD, Chairman of Nona Biosciences. "With the capabilities of Harbour Mice®, we look forward to empowering our partners in antibody drug discovery and development, and helping more patients benefit from cutting-edge technologies and therapies." "There is tremendous potential in antibody-based therapy, and I am very excited about this collaboration," said Simon Li, MD, PhD, CEO & CMO of Evive Biotech. "Evive Biotech's mission is to develop innovative biologic therapies for patients worldwide. We eagerly anticipate collaborating with Nona Biosciences to accelerate the discovery of innovative antibody therapies to benefit patients across the globe." About Nona Biosciences Nona Biosciences (a wholly-owned subsidiary of HBM Holdings Limited, HKEX: 02142) is a global biotechnology company committed to cutting-edge technology innovation and provides a total solution from "Idea to IND" (I to ITM), ranging from target validation and antibody discovery through preclinical research. The integrated antibody discovery services range from antigen preparation, animal immunization, highly robust antibody screening, to antibody lead generation and engineering, developability assessment and pharmacological evaluation, leveraging advantages of Harbour Mice® technology and the experienced therapeutic antibody discovery team. Harbour Mice® generate fully human monoclonal antibodies in a traditional two heavy and two light chain (H2L2) format, and a heavy chain only (HCAb) format. Integrating Harbour Mice® with highly robust antibody screening platforms, Nona Biosciences is focused on driving global inventions of transformative next-generation drugs. For more information, please visit: About Evive Biotech Evive Biotech (a subsidiary of Yifan Pharmaceutical Co., Ltd., SZSE: 002019) is a global biopharmaceutical company devoted to developing a portfolio of novel biological therapies for patients worldwide. We leverage our proprietary technology platforms to advance a series of innovative drug candidates for oncology, inflammatory and metabolic diseases. Founded in 2004, we currently have operations in the US, Singapore, and China. As the first biopharmaceutical company to build a platform bringing innovative therapies from China to the world, Evive adopts a holistic approach to drug development, combining exceptional research and commercialization capabilities with our world-class in-house regulatory expertise and extensive international management experience. Through partnerships with industry, physicians, and regulatory authorities, we strive to bring revolutionary remedies to the global market quickly and efficiently to address unmet medical needs, making a real and lasting difference to patients and their families worldwide. For more information, please visit: SOURCE Nona Biosciences