FDA发布个体化基因编辑疗法指南草案：罕见病新变体达标可免新增临床试验 CMS同步扩大疗法可及模式
美国卫生与公众服务部（HHS）10月27日宣布，食品药品监管局（FDA）发布一份针对个体化基因编辑疗法的指南草案，为治疗罕见遗传病患者的个性化基因疗法如何申报上市、获批后如何增补新变体提供明确框架；医疗保险和医疗补助服务中心（CMS）同日宣布，将把细胞与基因疗法可及性模式从镰状细胞病扩大到更多病种，帮助更多参加医疗补助（Medicaid）的患者用上这类疗法。
这份指南名为《个体化人类基因组编辑产品：生物制品许可申请提交与获批后管理的考量》。HHS介绍，部分罕见病由因人而异的基因突变引起，同一种疾病在不同患者身上的致病变体并不相同，一种疗法难以适用于所有人；个体化基因编辑疗法正是针对每位患者各自的遗传变体量身设计，业界此前一直希望FDA明确这类「每位患者略有不同」的疗法应如何申请生物制品许可（BLA）。
指南的核心是「个体化特征空间」（IFS）概念：申办方先在一份BLA中预先界定产品可以变化的边界，只要针对新患者做出的新变体落在这些边界之内，且实验室检测显示其安全性与活性达标，就可以把新变体补进同一份许可，不必再为每个变体重复开展临床试验。指南同时涵盖生产、安全检测（包括非预期的基因改变风险）、产品命名与标签等事项。FDA正就草案征求公众意见，意见可在《联邦公报》刊登后30天内、通过案件号FDA-2026-D-11783提交。
HHS部长Robert F. Kennedy, Jr.表示：「面对罕见遗传病的家庭理应有更多治疗选择，无论与他们患同一种病的人有多少。」FDA代理局长Kyle Diamantas表示，一刀切的疗法对罕见病患者行不通，监管也不应一刀切，这份指南在保持严格科学与有效性标准的同时给申办方以明确指引。FDA生物制品审评与研究中心主任Karim Mikhail称，这是FDA支持个体化疗法开发的关键一步，让包括目前无药可治的超罕见病在内的患者能更快获得可能改变人生的疗法。
CMS方面，其细胞与基因疗法（CGT）可及性模式由CMS代表各州Medicaid项目与药企谈判、以疗效为基础达成协议。首轮针对镰状细胞病疗法的评估显示，由CMS统一谈判减轻了各州的行政负担，并因汇集了参保人群而增强了议价能力。CMS计划在未来几个月发布新的制造商申请征集，把模式范围扩大、让谈判能在疗法获FDA批准后更早启动，也接受已获批疗法的申请。CMS局长Mehmet Oz表示，医学突破只有患者用得上才有意义，CMS要让罕见病患者、尤其是儿童，不因费用被挡在疗法之外。
FDA Issues Draft Guidance for Individualized Gene-Editing Therapies; CMS to Expand Cell and Gene Therapy Access Model
The U.S. Department of Health and Human Services (HHS) announced on October 27 that the Food and Drug Administration (FDA) has issued a draft guidance giving sponsors a clear framework for developing and winning approval of personalized gene therapies for patients with rare genetic diseases. The Centers for Medicare & Medicaid Services (CMS) said the same day it will expand its Cell and Gene Therapy (CGT) Access Model beyond sickle cell disease, to help more Medicaid patients reach such treatments.
The guidance, titled "Individualized Human Genome Editing Products: Considerations for BLA Submission and Postapproval Management," addresses therapies tailored to each patient's specific genetic variant. Some rare diseases are caused by mutations that differ from patient to patient, so a single treatment cannot work for everyone with the same condition, and sponsors had sought clear FDA guidance on how to obtain approval for a therapy that may look slightly different for each patient it treats.
Central to the framework is the "Individualized Feature Space" (IFS): a set of pre-defined boundaries describing how a gene-editing product may vary from patient to patient while remaining within the scope of a single Biologics License Application (BLA). When a new patient-specific variant falls within those boundaries and laboratory assays show adequate safety and activity, sponsors can add it to the BLA without performing additional clinical trials. The guidance also addresses manufacturing, safety testing including risks of unintended genetic changes, and product naming and labeling. FDA is inviting public comment on the draft, which may be submitted to docket FDA-2026-D-11783 within 30 days of publication in the Federal Register.
"Families confronting rare genetic diseases deserve more treatment options, no matter how few patients share their diagnosis," said HHS Secretary Robert F. Kennedy, Jr. Acting FDA Commissioner Kyle Diamantas said a one-size-fits-all approach to treatment does not work for rare diseases and neither should a one-size-fits-all approach to regulation. Karim Mikhail, director of FDA's Center for Biologics Evaluation and Research, called the guidance a critical step that can help patients, including those with ultra-rare conditions for which no treatment exists, access life-changing therapies more efficiently.
At CMS, the voluntary CGT Access Model has CMS negotiate outcomes-based agreements with manufacturers on behalf of state Medicaid programs. Its first evaluation found that CMS-led negotiations for sickle cell disease therapies eased states' administrative burden and strengthened their leverage by pooling beneficiaries. In the coming months CMS will issue a new Request for Applications to broaden the model's scope, enable negotiations to begin sooner after a therapy is approved, and welcome therapies already approved or licensed. "A medical breakthrough only matters to patients if they can get it," CMS Administrator Dr. Mehmet Oz said.
来源：GSM·美国（原文链接）
图片来源：美国卫生与公众服务部（HHS）总部Hubert H. Humphrey大楼，位于华盛顿。照片：Matthew Bisanz，CC BY-SA 3.0，经Wikimedia Commons。
