多数专家反对,3名评委辞职,FDA为何批准阿尔兹海默症新药?
FDA的加速审批项目 图:FDA
1.替代终点和疾病缓解直接有关:如果改善替代终点即可直接达到缓解疾病、逆转病程等目标,那么企业只需要提供药物改善替代终点的数据即可上市,且无需预先申请加速审批。这方面的典型代表就是治疗高血压的各类药物。根据FDA的有关指引,高血压治疗药物只需证明其可明显降低血压,即可在说明书上标明该药“降低血压可降低致命或非致命性心血管事件,主要是卒中、心肌梗死的风险”。
2.替代终点是疾病预后的有力标志物:对于一些病程缓慢的疾病,临床试验或许需要极长时间,但倘若此类疾病存在已知的预后生化标志物,那么企业就可以先证明药物可以改善预后生化标志物水平,获得加速批准后再进行更大规模的研究。这方面的典型案例是Intercept公司治疗原发性胆汁性胆管炎的奥贝胆酸(Obeticholic Acid),该药在临床研究中可有力降低患者的碱性磷酸酶水平,而早前的大量研究已经证实,该病患者的碱性磷酸酶水平越高,预后越差。
3.替代终点仅暂时反映了药物的有效性,但疾病缺乏治疗手段:这种“替代终点”通常用于抗肿瘤药物的上市申请中。某些肿瘤进展极快,但可能缺乏进行大规模试验的受试患者,对于治疗此类肿瘤的药物,肿瘤综合缓解率(ORR,指研究组中获得缓解的患者占整体患者的比例)、缓解持续时间(DoR,服用药物疾病缓解后的患者,疾病从缓解到再次进展的时间)等指标均可拿来作为“替代终点”,让药物尽快服务于缺乏希望的患者。
aducanumab在临床研究中使用了多种生物标志物作为研究终点,但它们的意义尚未明确。图:渤健公司
渤健公司公布的aducanumab的临床结果数据一览 图:渤健公司
在争议中批准的氟班色林,最终落得了一地鸡毛
[1]The U.S. Food and Drug Administration. FDA’sDecision to Approve New Treatment for Alzheimer’s Disease[EB/OL].[2021-06-07] https://www.fda.gov/drugs/news-events-human-drugs/fdas-decision-approve-new-treatment-alzheimers-disease[2]The U.S. Food and Drug Administration.Delivering Promising New Medicines Without Sacrificing Safety and Efficacy[EB/OL].[2019-08-27]https://www.fda.gov/news-events/fda-voices/delivering-promising-new-medicines-without-sacrificing-safety-and-efficacy[3]BioPharmaDive. FDA advisers vote againstBiogen's Alzheimer's drug, leaving its future in doubt[EB/OL].[2020-11-08] https://www.biopharmadive.com/news/fda-advisory-panel-vote-biogen-alzheimers-aducanumab/588580/[4]The U.S. Food and Drug Administration.Accelerated Approval Program[EB/OL].[2020-10-26] https://www.fda.gov/drugs/information-health-care-professionals-drugs/accelerated-approval-program[5]Nisbet RM, Götz J. Amyloid-β and Tau inAlzheimer's Disease: Novel Pathomechanisms and Non-Pharmacological TreatmentStrategies[J]. J Alzheimers Dis. 2018;64(s1):S517-S527. doi:10.3233/JAD-179907.[6]Hardy JA, Higgins GA. Alzheimer'sdisease: the a-myloid cascade hypothesis[J]. Science. 1992 Apr10;256(5054):184-5. doi: 10.1126/science.1566067.[7]Sevigny J, Chiao P, Bussière T, et al.The antibody aducanumab reduces Aβ plaques in Alzheimer's disease[J]. Nature.2016 Sep 1;537(7618):50-6. doi: 10.1038/nature19323.[8]Knopman DS, Jones DT, Greicius MD.Failure to demonstrate efficacy of aducanumab: An analysis of the EMERGE andENGAGE trials as reported by Biogen, December 2019[J]. Alzheimers Dement. 2021Apr;17(4):696-701. doi: 10.1002/alz.12213.[9]Nevens F, Andreone P, Mazzella G, et al;POISE Study Group. A Placebo-Controlled Trial of Obeticholic Acid in PrimaryBiliary Cholangitis. N Engl J Med. 2016 Aug 18;375(7):631-43. doi:10.1056/NEJMoa1509840.[10] Bhatt DL, Stone GW, Mahaffey KW, et al;CHAMPION PHOENIX Investigators. Effect of platelet inhibition with cangrelorduring PCI on ischemic events[J]. N Engl J Med. 2013 Apr 4;368(14):1303-13.doi: 10.1056/NEJMoa1300815.[11]Haeberlein, S.B., von Hehn, C., Tian,Y., et al. Emerge and Engage topline results: Phase 3 studies of aducanumab inearly Alzheimer’s disease[J]. Alzheimer's Dement., 16: e047259. doi:10.1002/alz.047259[12]Biogen Inc. EMERGE and ENGAGE ToplineResults: Two Phase 3 Studies to Evaluate Aducanumab in Patients With Early Alzheimer’sDisease[EB/OL].[2020-05-09] https://investors.biogen.com/static-files/8e58afa4-ba37-4250-9a78-2ecfb63b1dcb[13]The U.S. Food and Drug Administration.FDA grants accelerated approval to new treatment for advanced soft tissuesarcoma[EB/OL].[2019-02-22] https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-new-treatment-advanced-soft-tissue-sarcoma
一次产下10胞胎!多胞胎真的想生就能生吗?18年了,FDA终于批了一个老年痴呆新药
神经科医生患老年痴呆后,把自己的病例发了论文……
点击“阅读原文”,查看更多资讯~