Ataluren

摘要：威斯康星州共和党参议员罗恩・约翰逊宣布调查 FDA 近期罕见病药物审批驳回事件，导火索是 uniQure 亨廷顿病基因疗法的临床试验要求引发激烈分歧，多款罕见病药物接连遭拒或撤申请。FDA 坚称审批决策合规，却未提供关键佐证数据，其标榜的 “激进透明” 也因执行不一遭质疑，药企、患者与监管机构的矛盾持续升级。 颅骨钻孔争议，议员痛批官僚 罗恩・约翰逊最近的火气，全撒在了 FDA 身上。这位执掌参议院常设调查小组的议员，直接把 FDA 要求 uniQure 为亨廷顿病基因疗法做假手术对照试验的决定，骂成了 “官僚白痴”。 “你让患者挨颅骨钻孔的假手术？这太离谱了。” 约翰逊的质问直截了当。这款疗法本就需要在头骨打孔、向颅内注射药物，uniQure 早在 3 月 2 日就明确表态，这样的对照试验会给患者带来巨大风险，甚至触及伦理底线。 FDA 这边却有不同说法。一位匿名高层 —— 外界普遍认为是即将离职的疫苗与细胞基因疗法主管维奈・普拉萨德 ——3 月 5 日出来辩解，称对照组只是给患者麻醉后在头皮划 1-3 道小口，并非颅骨钻孔。 但这番解释没平息争议。隔天就传出消息，普拉萨德将在 4 月底离职，这已是他第二次离开 FDA，其继任者目前还在物色中。约翰逊直言，FDA 这副样子，看着就像在找借口拒绝药企。他已经要求查看 FDA 近期发出的完整审批回复函，甚至不排除传唤 FDA 高层到参议院作证。多款药折戟，专家患者皆心寒 亨廷顿病疗法的争议，只是冰山一角。其实早在 2 月底，佛罗里达州参议员里克・斯科特主持的听证会上，FDA 就因罕见病药审批问题，被医生、药企和患者代表集体质疑。 约翰逊当时也在听证会上发声，矛头直指 FDA 去年 11 月驳回 Biohaven 脊髓小脑共济失调药物 troriluzole 的决定。哈佛医学院神经学教授杰里米・施马曼的话，听着就让人揪心。2023 到 2025 这两年，他和 17 位同行联名给 FDA 写了 6 封信，只求 FDA 重新审核这款药，哪怕获批后再做上市后研究也行，可始终没收到任何回复。 更让人无奈的是 PTC Therapeutics 的 Translarna。这款治疗杜氏肌营养不良的药，在 2 月中旬因 FDA 反馈不佳，药企直接撤回了上市申请。约翰逊很快就要和这款药的患者及家属开一场新闻发布会，那些即将失去用药希望的家庭，成了这场审批争议里最无辜的受害者。 约翰逊想不通，为什么 FDA 就是不肯听一线专家的话，明明这些药物能实实在在帮到罕见病患者。FDA 硬刚却缺实证，透明化成空话 面对接连的质疑，美国卫生与公众服务部发言人安德鲁・尼克松替 FDA 做了回应。他说 FDA 始终站在科学家这边，审批理由都会在完整回复函里详细说明，而且这些函件如今首次对公众开放，这是 FDA 在推进 “激进透明”。 可实际情况并非如此。特朗普政府二度执政后，FDA 承诺审批回复函与药企同步公开，但执行起来却毫无章法，公开的内容和时间都没个准数。尼克松还称，本届政府任内 FDA 的审批通过与驳回数量，和过去十年的历史数据一致，去年 12 月生物制品评估和研究中心的审批数量还创了纪录。 但当被要求拿出具体数据佐证时，FDA 却哑口无言，拿不出任何资料。面对罕见病领域的强烈反对，尼克松只强调 FDA 的职责是守护患者和公共健康，还搬出了 CRISPR 疗法的审批框架草案，称现在的 FDA 比以往任何时候都更努力推进超罕见病疗法研发。 这些话听着漂亮，却没多少说服力。坦白讲，罕见病患者等不起，药企的研发投入也耗不起。FDA 口中的科学严谨，在患者和专家眼里，有时更像冰冷的官僚流程。 约翰逊的调查已经箭在弦上，这场围绕罕见病救命药的拉扯，到底是 FDA 在坚守科学底线，还是官僚主义拖慢了药物上市的脚步，或许只有等调查结果出来，才能有一个让人信服的答案。 参考来源：https://www.fiercebiotech.com/biotech/republican-senator-slams-fda-rare-disease-rebuffs-pledges-investigate-recent-actions 识别微信二维码，添加生物制品圈小编，符合条件者即可加入 生物制品微信群！ 请注明：姓名+研究方向！ 版 权 声 明 本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观不本站。

Wisconsin Sen. Ron Johnson told Bloomberg that he may call on top FDA leaders to testify before the Senate’s Permanent Subcommittee on Investigations.\n As tensions around the FDA continue to escalate, a Republican U.S. senator has announced an investigation into recent approval rejections for rare disease candidates, according to Bloomberg News.  Wisconsin Sen. Ron Johnson is asking to see several of the complete response letters that have been delivered of late and also told Bloomberg that he may call on top FDA leaders to testify before the Senate’s Permanent Subcommittee on Investigations, which Johnson chairs.The probe comes on the heels of heightened interactions between gene therapy developer uniQure and the FDA as an unnamed senior agency official—widely believed to be the now-departing Vinay Prasad, M.D.—defended the FDA’s demand that the biotech launch another sham-controlled trial for its Huntington’s disease candidate. The one-time uniQure therapy is given directly into the brain through small holes in the skull. Now, Johnson is categorizing the request for a new trial as “bureaucratic idiocy,” according to Bloomberg. “You’re expecting people to go through sham surgeries where they get holes drilled in their heads?” Johnson said to the outlet. “That’s just unbelievable.” On March 2, uniQure leaders argued that a sham-controlled study “could impose significant risks and burden to patients—some might even consider this trial design to be unethical.” A few days later, the anonymous FDA official denied that the control group would require that patients get holes drilled in their heads. “We asked uniQure to take their product and randomize patients to getting the treatment the way they give the treatment, which requires a skin incision, a hole in the skull and an intracranial injection of the product, versus a control arm, where all they do is anesthetize the patient and put one to three nicks in the scalp,” the unknown official said on March 5. “We did not ask them to compare against a partial sham burr hole.”One day later, news broke that Prasad would be departing his role as the FDA’s top regulator of vaccines and cell and gene therapies at the end of April—the second time the leader has left the agency. A search is currently underway for Prasad’s successor.“The stories are so outrageous,” Johnson said to Bloomberg. “It just appears that they’re looking for excuses to say no.”In response, Department of Health and Human Services spokesperson Andrew Nixon told Fierce that the FDA “stands by the scientists evaluating these applications and each rationale is explained in detail through CRL’s, which, for the first time, are made available to the public.” Under the second Trump administration, the drug regulator pledged to publicly release CRLs at the same time they are issued to sponsoring companies, part of what the FDA calls a push toward “radical transparency.” The agency has released batches of certain rejection letters, but it has not been consistent in what is published and when. “The number of FDA approvals and rejections under this administration are consistent with historical data over the last decade. In fact, CBER had a record number of approvals in December,” HHS’ Nixon said.The agency did not provide the referenced data behind this claim when asked.When asked about the intensifying pushback from the rare disease community, the HHS spokesperson said, “Our obligation is to patients and public health, and we remain committed to a regulatory approach that brings safe, effective individualized treatments to patients who urgently need them.”He also cited the agency’s plausible mechanism framework, which is draft guidance for an approval pathway that could see custom CRISPR therapies formally embraced by the agency. “This FDA is doing more than any other time in history to help speed up the development of ultra-rare disease cures for the American people,” the spokesperson said. In late February, a panel of physicians, biotech leaders and patient advocates took aim at the FDA during a Senate hearing chaired by Sen. Rick Scott, R-Fla., on how the agency’s bureaucracy affects innovation.Sen. Johnson spoke during that hearing, which included a discussion of the FDA’s November rejection of Biohaven’s experimental drug, troriluzole, for spinocerebellar ataxia. “I wrote six letters to FDA leadership between 2023 and 2025, cosigned by 17 ataxia colleagues asking FDA to review the application again and work with Biohaven to make the drug available [and], if necessary, performing post-marketing studies. I never heard back,” Jeremy Schmahmann, M.D., a neurology professor at Harvard Medical School and founding director of Massachusetts General Hospital’s Ataxia Center, said during the hearing.Johnson told Bloomberg that he is also upset about the spinocerebellar ataxia rebuff, adding that he doesn’t understand why FDA officials aren’t listening to specialists who say rare disease candidates are helping their patients.The senator will be holding a press conference alongside patients and families who are losing access to ataluren, also known as Translarna, a treatment designed to treat Duchenne muscular dystrophy (DMD). In mid-February, drugmaker PTC Therapeutics revealed that it withdrew its FDA application for Translarna in nonsense mutation DMD after receiving feedback from the regulator. As of publication, Johnson’s office has not responded to Fierce Biotech’s inquiries for additional comment.