Onasemnogene abeparvovec

6月5日，美国FDA在华盛顿召开了一场“细胞与基因治疗( CGT) 圆桌会议”，来自监管部门、学界、产业界和患者团体的代表就CGT产品研发中的监管障碍展开讨论。会上，卫生与公众服务部（HHS）部长肯尼迪呼吁参会者列举应取消的监管规定。他援引美国总统行政令指出：“特朗普总统下令，在我们制定一项新法规时，必须废除10项现行法规”，并要求专家提供建议。FDA局长马蒂·马卡里在开场白中表态将认真听取各方意见，他表示FDA代表“科学的金标准和常识”（gold-standard science and common sense），愿意听取各界意见并挑战根深蒂固的假设。FDA局长承诺要与研发者、发明者建立牢固伙伴关系，减少无谓的程序浪费，加速那些对公众有意义的疗法获批。细胞与基因治疗技术及其前景细胞与基因治疗（CGT）是一类利用活细胞或基因编辑技术来治疗疾病的新兴疗法，近年来在罕见病和肿瘤领域取得突破性进展。例如，CAR-T细胞疗法（如2017年获批的Kymriah和2018年的Yescarta）已显著改善某些血液癌症患者的生存率；基因替代疗法（例如2017年获批治疗视网膜疾病的Luxturna、2019年获批治疗脊髓性肌萎缩症的Zolgensma）也改变了患者预后。最新的基因编辑疗法Casgevy是FDA首个获批的CRISPR疗法，用于镰状细胞病，展示了对单基因遗传病“根治”潜力。此外，费城儿童医院研究人员近期为一名患有极罕见代谢缺陷的婴儿“KJ”量身定制了体内CRISPR治疗，挽救了这个几乎无救治方案的患儿。总体来看，美国FDA对CGT的关注度和审批速度正在加快：据统计，2024年有8个创新CGT产品获批，至少6个已上市CGT的适应症获扩展批准，显著高于往年水平。CGT研发的主要挑战尽管前景广阔，CGT研发面临一系列独特难题：生产和质量控制（CMC）：CGT产品通常是复杂的活细胞药物或基因载体，需要精细的工艺控制和个性化制造。与传统小分子药物不同，这些疗法对生产过程、原材料来源、批次间一致性等要求极高。FDA指南指出，早期CGT产品开发常遇到常规药物中很少出现的CMC问题。如何确保产品在制造、运输和储存过程中保持稳定、安全，是监管部门和生产者共同面临的挑战。临床试验设计：由于靶向对象多为罕见病患者或高度个性化疗法，患者数量极其有限，随机对照试验难以实施。专家们建议更多采用创新设计，如单臂研究、历史对照组或基于生物标志物的入组标准等。FDA领导层也表示愿意探索替代试验模式。例如，一位专家指出，美国CGT临床审批过慢，一些研究者宁愿赴境外开展试验。他提议借鉴中国“双轨制”模式：早期探索性人体试验只需伦理委员会审批，FDA仅在进入大规模多中心研究阶段时介入审批。这与FDA内部讨论内容不谋而合——如何降低临床试验设计的僵化要求，让创新更早进入人体验证。疗效终点和替代指标：很多罕见病和CGT研究缺乏明确的替代终点，因此研发者呼吁监管机构接受诸如生物标志物等替代疗效指标。FDA新任CBER主任文奈·普拉萨德（Vinay Prasad）就表示，将利用生物学效应作为早期信号，“快速提供”罕见病疗法。他承诺FDA会在看到“疗效的第一丝希望”时就行动起来，不再无谓等待。这从监管侧释放出信号：对于严重、无法治愈的疾病，政策有可能允许以较低标准批准，后续通过真实世界数据和后期确认试验补充评估。综上，CGT开发涉及创新疗法的多层面难题，需要监管部门在灵活审评与科学严谨之间找到平衡。FDA监管难题——借鉴中国模式？在此次圆桌会议上，与会各方对FDA现行监管流程表达了广泛关注，呼吁改革以消除冗余审批环节，缩短疗法上市时间。宾夕法尼亚大学的Carl June直言：美国CGT研发过程“太慢、太昂贵、缺乏灵活性”，研究人员不得不“把临床试验搬到海外”。他建议参考中国做法，将早期研究置于伦理监管之下，仅在疗法进入多中心大规模研究时才由FDA介入审批。这一观点反映出产业界对现行监管要求的焦虑——如果美国审批速度落后，可能会失去技术领先地位。与美国相比，中国近年来在细胞与基因治疗领域也迅速行动。自2017年起，中国实行细胞治疗双轨制监管：临床研究可走“科研单元”（相当于由医院伦理委员会批准）或者“注册临床试验”（由国家药监局NMPA审批）两条路径。这使中国CGT研发呈现爆发式增长：截至2024年，中国CGT管线规模跃升至全球第二，仅次于美国。中国已批准多项国内研发的细胞疗法和基因疗法，如近期，距离2024年12月FDA批准首款间充质基质细胞疗法 Ryoncil 仅相差不到半个月时间，2025年1月，NMPA通过优先审评审批程序附条件批准国内首款间充质干细胞治疗药品艾米迈托赛注射液上市，这是一种罕见病用药，用于治疗14岁以上因血液系统疾病造成造血干细胞移植后出现的并发症--急性移植物抗宿主病。此次圆桌会中，参与者建议部分放宽这一框架，例如借鉴中国模式让早期研究先行。有观点认为，美国监管改革可以结合两种模式：对无替代疗法、预期获益重大的罕见病，允许条件性早期获批，同时强化上市后真实世界证据收集；对于生产过程高风险的疗法，则维持严格监督。中美在监管思路上的差异，也促使FDA反思其政策：美国的流程“显得太慢”，而其他国家——尤其是中国——让创新更容易实现。换言之，CGT领域的国际竞争格局推动美国监管机构考虑转变策略。参考资料：FDA官方网站、行业媒体和政府报告等。https://www.raps.org/news-and-articles/news-articles/2025/6/stakeholders-urge-fda-to-update-cgt-regulations-tohttps://endpoints.news/fdas-vinay-prasad-says-he-will-rapidly-push-forward-rare-disease-advances/https://www.senate.gov/legislative/LIS/roll_call_votes/vote1191/vote_119_1_00293.htmhttps://www.gao.gov/products/gao-25-106980

iStock, Perception7 Gene therapies have ridden investor mania to huge valuations but commercialization challenges have pushed market caps to the floor. At an FDA roundtable last week, FDA leaders promised faster approvals and broad support to the industry. Following comments from FDA Commissioner Marty Makary and Center for Biologics Evaluation and Research Director Vinay Prasad signaling their support for rare diseases, the regulator hosted a roundtable last week to discuss the state of cell and gene therapies—still relatively young modalities often targeting rare indications. As the healthcare administors listened to feedback from the industry, they promised to help the technology reach its full potential. “We’re going to do everything in our power to sweep away the barriers from you getting those solutions to market and getting them funded and do everything that we can to support you,” Health and Human Services Secretary Robert F. Kennedy Jr. said at the event . This comes after Makary said in April that the agency would roll out a type of conditionalapproval pathway for therapies based on a “plausible scientific mechanism” for rare, incurable conditions. It also comes at a much-needed time. The gene therapy space, in particular, has seen one hit after another in recent months and faces commercialization challenges highlighted by bluebird bio’s go-private deal earlier this year. Combined with a patient death tied Sarepta’s Duchenne muscular dystrophy gene therapy Elevidys in March, the departure of gene therapy’s regulatory champion Peter Marks and other macro headwinds, the sector is keen to see the tides turn. “Right now we’re in a cold winter,” Seth Ettenberg, CEO of Bayer gene therapy subsidiary BlueRock Therapeutics, told BioSpace . “Interest rates are up, companies are doing add-ons, valuations are coming down as we speak.” But inside industry there’s hope that summer will come sooner rather than later—and last week’s roundtable disussion appeared to analysts to be a net positive for the space, including such companies as Vertex , uniQure and Denali . “The FDA Cell and Gene Therapy Roundtable was bullish for the space, particularly for those focused on rare disease, in our view,” Stifel wrote in a note to investors on June 5. Bluebird Bought In February 2025, investment firms Carlyle and SK Capital Partners made a buyout offer to bluebird bio for a scant $30 million. Though the number has crept up to $48.9 million in a new deal, the whole ordeal came as a shock to the industry, given that the company was once worth two orders of magnitude more, valued at $11.5 billion in March 2018. With their purchase, bluebird’s new owners will get a handful of cutting-edge gene therapies with valuable FDA approvals for sickle cell disease, β-thalassemia and cerebral adrenoleukodystrophy. But even with those marketed treatments, the biotech couldn’t bridge the cash gap that loomed large late last year. Bluebird is not alone in its struggle. At a glance, the valuations of almost all high-pro therapy companies over the last five years have gone from the atmosphere to the dirt. The medical value of gene therapies continues to be obvious—look no further than last month’s news of baby KJ’s personalized CRISPR treatment —but the business value faces serious challenges. Investments in cell and gene therapy (CGT) have been similarly challenged. Prior to the COVID-19 pandemic, investment in the space was consistently in the double-digit billions, thanks in large part to clinical trial results out of Ohio State University. In November 2017, pediatrics professor Brian Kaspar and AveXis published the results of a Phase I trial of 15 infants with spinal muscular atrophy type 1. A devastating disease, patients often do not survive past the age of two; without ventilatory support, 92% of patients died by 20 months of age. In the trial, however, every single patient was still alive at 20 months. “That was the moment where people said, ‘Oh my god, gene therapy is actually working, and working in a monumental way,’” Graig Suvannavejh, managing director at Mizuho Securities, told BioSpace . The reward for AveXis was immediate. The following year, Novartis bought AveXis for a bellowing $8.7 billion, a 72% premium over the biotech’strading price and a valuation based entirely on the promise of that Phase I trial, according to Suvannavejh. AveXis’ treatment, onasemnogene abeparvovec, was approved in 2019 and is now sold by Novartis under the brand name Zolgensma. “At that moment, everyone said, ‘I’m starting a gene therapy company,’” Suvannavejh said. “The business model seemed like just you run one trial and get bought for $9 billion.” Indeed, investment jumped a massive 512% the very next year and maintained similarly high levels until it doubled in 2021 during the biotech boom of the pandemic. But like all areas of biopharma, CGT felt the bubble burst. And in gene therapy specifically, investor nervousness pervades the conversation—especially amid the fallout of bluebird and other examples of commercialization challenges of successful therapies. Baked In Problems Some of the difficulty in getting the CGT space off the ground is baked into the types of diseases most treatments are currently targeting. “Gene therapies are often difficult case studies,” BlueRock’s Ettenberg said. “They have large price points and small patient populations.” The incidence for many diseases targeted by CGT puts them squarely in the rare diseases category. Spinal muscular atrophy occurs in about one of every 10,000–20,000 births. Beta-thalassemia, which bluebird’s beti-cel therapy treats, occurs in about 1.5 of every 100,000 births. Contrast those numbers with the cost of developing these therapies and the challenging economics of the space become clear. One recent analysis put the cost of developing a new cell or gene therapy at about $2 billion , which significantly outstrips the average cost of developing any new drug, which ranges from $100 million to $800 million. “What we’re coming to recognize is that the initial capital to get through preclinical and manufacturing is larger than other modalities,” Ettenberg said. Given the high investment and often small patient populations, it’s no surprise that many gene therapies have exorbinate price tags. Bluebird’s beti-cel, for instance, costs $2.8 million for one dose. And that’s not even the most expensive treatment. Orchard Therapeutics’ Lenmeldy for pediatric metachromatic leukodystrophy costs a whopping $4.25 million, while Sarepta’sElevidys costs $3.2 million. New regulatory action could help here. Analysts at Stifel noted that last week’s CGT roundtable included “plans to incentivize the reimbursement of CGT products.” These potentially include novel, innovative payment models, the group continued, “which HHS views as ROI-positive from a healthcare net-spend perspective.” Outside of rare diseases, those in the field look for gene therapies to break into more common disease spaces, bringing more money into the space and potentially bringing down costs across the board as the field’s infrastructure improves, knowledge of how to manufacture these therapies becomes more widespread and the treatments themselves become more common. “My hope is that gene therapy makes inroads in oncology,” , Omar Dabbous, former vice president at Novartis Gene Therapies, told BioSpace , adding that “advances in the science in oncology translates into benefits.” The FDA’s roundtable discussion has further buoyed the sector’s spirits. “The comments from the FDA leadership are very encouraging,” Beam Therapeutics CEO John Evans told BioSpace in an email. “Accelerating cures for serious diseases is a compelling area for FDA to focus on, and they can play a pivotal leadership role in advancing some of these policy changes.” Majors agreed. “We don’t recall a time where there was this level of alignment among the highest levels of government around the promise of CGT. Stakeholders, including investors, are taking notice.”