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iStock, ALXR The approval of Mirum Pharmaceuticals’ ALK2 inhibitor for fibrodysplasia ossificans progressiva on Friday adds a third option for patients who had long been without any treatments, joining Regeneron’s recently approved Pasatru and Ipsen’s Sohonos. Mirum Pharmaceuticals notched an FDA approval Friday for zilurgisertib—to be marketed as Atebrioz—for the treatment of an ultra-rare bone-forming disease that for decades had no treatments. Mirum joins Regeneron and Ipsen in the tiny space as it brings a third option to the market in as many years. Colloquially called “ stone man syndrome ,” fibrodysplasia ossificans progressiva (FOP) causes bone formation within connective tissue including tendons, ligaments and muscles—known as heterotopic ossification (HO)—leading to pain, stiffness and immobility over time. “To put it simply, it’s a terrible disease,” Mirum CEO Chris Peetz told BioSpace ahead of the company’s new approval. “Even bumping into something and bruising can result in signaling that turns soft tissue into bone and accumulates over time. Into young adulthood, it can become life-threatening, and before these treatments, there was nothing that could stop progression.” The genetic disorder is estimated to affect one in a million people globally. FOP specialist Angela Cheung, director of the osteoporosis program at University Health Network in Toronto, described the patient experience. “People get trapped in their own skeleton, like tin soldiers, and they progressively get worse over time with an average life expectancy of 56 years, many even younger.” Cheung called the 20-year-old discovery of the ACVR1 gene, which causes this abnormal signaling, “groundbreaking,” adding that the knowledge enabled clinicians and researchers to develop therapies for patients with the disease. Ipsen’s Sohonos was the first to market, approved by the FDA in August 2023, then Regeneron’s Pasatru followed just last month. Mirum’s approval has thus now tripled the available options for patients with FOP in just five weeks’ time. Cheung told BioSpace that in a disease like FOP, patients need options, and that the three drugs available, each of which works in a different way and is “not for everyone,” offer just that. Atebrioz, approved by the FDA for patients 12 years and older, is a once-daily pill that inhibits the activin receptor-like kinase 2 (ALK2) protein, which has been found to cause abnormal bone growth in FOP. Originally discovered by Novartis and later licensed by Incyte for clinical development, rare disease–focused Mirum gained full ownership of Atebrioz in April. Friday’s approval was based on data from Cohort 1 of the Phase 2 PROGRESS study , in which treatment with Atebrioz elicited an 81% reduction in new lesion volume and a 99% reduction in total volume compared with placebo at 24 weeks, meeting the primary endpoint. These treatment effects were maintained through week 48 of an open-label-extension study, according to a press release issued by Mirum and Incyte on Friday. The drug was generally well tolerated, the companies said, with only mild or moderate side effects, including headache, joint pain, respiratory infection, nosebleed and nausea. There were no adverse events that led to treatment discontinuation or dose reduction. Rare diseases Regeneron wins FDA approval to challenge Ipsen for rare bone disease market Regeneron’s Pasatru is the second fibrodysplasia ossificans progressiva drug approved in the U.S., following the 2023 approval of Ipsen’s Sohonos. August 20, 2026 · 2 min read · Nick Paul Taylor Read more Paving the way Peetz credits a small but vocal patient advocacy group, the International FOP Association, for putting FOP on the clinical map and guiding drugmakers’ efforts from a patient perspective. Mirum, which has three other rare disease drugs on the market, has learned how to bring these therapies to even the smallest populations. “I’m really proud of what we’ve created as a platform to find these great medicines that fall through the cracks,” Peetz said. “Things that look like maybe they’re too small but have tremendous patient impact.” In blazing the trail for FOP therapies, Ipsen met with a difficult path marked by missed clinical endpoints and an initial FDA rejection before ultimately squeaking Sohonos over the regulatory finish line. Sohonos, a daily pill that suppresses cartilage and bone development, reduced the volume of new bone growth by 54% in the Phase III MOVE trial . Despite being the first and only treatment for the disease, Sohonos came with risks that included early growth plate closure in children due to changes in bone formation. An advisory committee in June 2023 voted in support of the benefit-risk profile, leading to the drug’s approval in girls 8 years and older and boys 10 years and older. Sales of Sohonos, which was first approved in Canada in early 2022, dwindled even before competition entered the scene, however, with an almost 50% decline reported year-over-year in the first quarter of 2025. In the first half of 2026 , the drug was lumped into Ipsen’s $13.4 million rare disease portfolio. The FDA approval of Regeneron’s infused antibody Pasatru for adults with FOP marked the second treatment for FOP. In the Phase 3 OPTIMA trial , Pasatru significantly reduced the number of lesions in patients compared to placebo. Aris Economides, Regeneron’s vice president of research, points to early mouse models developed by his team that made clinical progress in FOP possible, providing insights into the specific ligands that caused an abundance of bone formation. “With this antibody, you completely block this heterotropic bone from forming in the mouse model, which told us that this was ligand-dependent, and not based on the receptor,” Economides said of Pasatru. This mechanism is more discerning than Sohonos’, he added, with Ipsen’s drug operating more broadly on bone formation. Pasatru’s FDA nod covers adults with the disease, but because FOP is a progressive genetic condition that begins from birth, Regeneron is exploring pediatric use in a Phase 3 study called OPTIMA 2 set to begin later this year, according to a spokesperson. Mirum is also conducting clinical trials in children as young as 2 years. Finding patients Peetz credits Atebrioz’s strong clinical data for helping to forge a clear regulatory path for the drug, particularly at an FDA that has recently pushed for rare disease reform . “If the data is clear in a rare disease, there are pathways to get medicine to patients in a reasonable amount of time, and to not put more draconian, larger indication standards on it,” Peetz said. Atebrioz previously received the FDA’s Fast Track and Orphan Drug designations. But with the approval now in hand, Mirum now embarks on a journey to bring the drug to patients. Even with “striking data,” that’s no easy task in such a small population, Peetz acknowledged. “Our biggest focus has been how quickly we can handle this transfer from Incyte to Mirum to get the drug out to patients, so expect that to happen in October,” he said. Another important part of access is price. Rare disease drugs often come with a hefty price tag, and treatments for FOP are no different. Sohonos kicked off at launch with a $624,000 annual list price , and Regeneron’s will start with its own list price of $1.4 million annually varying by dose, a company spokesperson said. Both drugmakers acknowledge the significant cost based on years of R&D and offer patient support programs. Mirum, which predicted peak sales of more than $200 million earlier this year for Atebrioz, has not yet revealed a list price and will announce the cost when it becomes available in October, Peetz said. The therapy is expected to be available through the company’s Mirum Access Plus (MAP) patient support program, according to Friday’s release, with eligible patients paying as little as $0 per month. “Access is a big thing,” Cheung said. “The companies have to get back their investment in research and development, but when you make it too high, it’s never going to work.”

北京必诺达 · 注册科学观察 国内最专业的医药注册公众号 · 全球视野，科学客观 栏目二 · 新药批准深度解读 ｜ 第 030 期 · 2026-09-27 结论卡 · 本期一句话 Atebrioz 于 9 月 25 日获批，靠的不是它自己预设的主要终点——那个终点 P=0.0986，没过线。FDA 改用了"新发异位骨化总体积"这把连续尺子（名义 P=0.004）批准。这不是终点偷换，而是罕见病小样本下比例型终点的天然脆弱。三款 FOP 药同场，Atebrioz 用口服 + 12 岁下限站住了位置。新药批准深度解读｜第 030 期：Atebrioz（zilurgisertib）——一款"主要终点没过线"却拿到常规批准的罕见病药一分钟速读批准 ：2026 年 9 月 25 日，FDA 批准 Atebrioz（zilurgisertib），用于减少 12 岁及以上纤维发育异常性骨化（FOP）患者新发异位骨化（HO）总体积。依据 ：II 期 PROGRESS 试验 Cohort 1（n＝63，双盲安慰剂对照 24 周）。两组数字 ：预设主要终点（第 24 周出现新发 HO 病变者比例）3.1% vs 16.7%，P＝0.0986，未达统计学显著；FDA 采信的"新发 HO 总体积变化"为 −3.2 cm³ vs 安慰剂 +24.6 cm³，名义 P＝0.004。格局 ：FOP 三年内从零获批到三药同场——2023 年 Ipsen 的 Sohonos、2026 年 8 月 Regeneron 的 Pasatru、以及今天的 Atebrioz。为什么值得看 ：一个试验里两个数差距如此之大，逼出的问题是——当样本量只有 63，终点应该怎么选。一、机制与定位：ALK2 上的第二个节点 Atebrioz 是口服小分子 ALK2（activin receptor-like kinase 2）抑制剂。ALK2 在多数 FOP 患者中异常激活，驱动本不该骨化的肌肉与韧带形成异位骨。阻断这个受体，等于在信号链的上游关闸。 它的同靶点前辈 Pasatru（garetosmab）走的是另一头：不是阻断受体，而是阻断与 ALK2 结合的配体激活素 A（activin A）。两个药在同一条通路的相反两端。专家视角 ：机制差别最终要翻译成标签人群的宽窄。Pasatru 只能覆盖肌肉注射给药、标签限于成人；Atebrioz 是每日一次口服、标签下探到 12 岁。同一个通路，一个卖的是给药方式，另一个卖的是年龄下限。二、未满足需求与疾病负担 FOP 极其罕见：全球约 900 例，美国约 300 例。疾病的过程是把肌肉、肌腱、韧带逐段落成骨，且以不可预测的体积发作——患者可能一夜之间活动度显著下降，随着骨量增加，关节强直、神经受压、慢性疼痛接踵而至。 Mirum 在过去五年对患者图谱的研究里有一个判断：临床上在试验方案里的 FOP 患者，比在用已上市药物的更多。这句话是它敢把适应症做窄、把终点选严的商业前提。三、PROGRESS 怎么设计：63 例撑起一份标签 Cohort 1：63 例 12 岁以上患者，1:1 随机，双盲、安慰剂对照，24 周，治疗组 32 例、安慰剂组 31 例，基线平均年龄约 21 岁。双盲期结束后进入单臂开放延长期，全部接受 100 mg 每日一次。 推荐剂量：100 mg，口服，每日一次，餐前餐后均可。注册知识库提示 ：这个样本量决定了后面所有数字的命运。63 例、两组各约一半，任何"事件发生比例"型终点能落到的事件数都只有个位数。这不是试验做得不小，而是罕见病注册的硬约束——它直接决定了终点该怎么选。四、两个终点，两个数：P＝0.0986 与 P＝0.004 的分工 这是本期最值得细看的一节。同一个试验里，FDA 拿到了两组数字： 终点 试验组 安慰剂组 结果预设主要终点 ：第 24 周出现新发 HO 病变的患者比例 1 例（3.1%） 5 例（16.7%） 相对降低 81%，P＝0.0986，未达统计学显著FDA 采信的终点 ：新发 HO 总体积变化 −3.2 cm³ +24.6 cm³ 名义 P＝0.004 关键次要终点：新发 HO 病变平均体积 0.003 cm³ 6.57 cm³ 降幅 >99%，名义 P＜0.0001 年化新发 flare 2.34 4.55 — 三点必须讲清： 1. P＝0.0986 是真的没过线，不是"接近显著"的修辞。在 0.05 的门槛下，它落在门外。 2. −3.2 vs +24.6 cm³ 是名义 P 值（nominal），未做多重性校正——它比"已校正的 P"要乐观一些，但仍远低于 0.05，且方向明确。 3. FDA 的批准建立在这一个连续型终点上，而不是那个比例型主要终点。专家视角 ：这不是终点偷换，而是比例型终点在小样本下的天然脆弱——当事件数是 1 对 5，任何统计模型都很难把它推过 0.05，哪怕绝对差距看起来有 81%。真正把证据撑住的是"体积"这个连续量：它把每个人的测量信息都用上了，而不是只数人头。对做罕见病的人，这是一条可复用的判断：人群极小时，优先选择能利用连续信息的终点，并把主要终点的预设写清。五、第 48 周：交叉之后发生了什么 24 周双盲期结束后，安慰剂组交叉接受治疗。至第 48 周： 61 例有全身 CT 数据的患者（含交叉者）未观察到新发 HO 病变； 第 24→48 周，持续治疗组总体积平均变化 −6.37 cm³，交叉组 −5.32 cm³。 两组数值接近，治疗效应在交叉后没有崩塌——这是 FDA 判断"效应不是安慰剂假象"时最看重的旁证之一。专家视角 ：交叉设计能出这种结果，前提是疗效评估靠的是定量影像而不是主观量表。FOP 用全身 CT 量体积，交叉后的数据仍然可信；换成疼痛评分或功能量表，交叉几乎一定会毁掉效应估计。六、三药同场：与 Sohonos、Pasatru 的对照 Sohonos（palovarotene） Pasatru（garetosmab-grts）Atebrioz（zilurgisertib） 批准 2023 2026-08-192026-09-25 机制 RARγ 激动剂 抗 activin A 单抗ALK2 小分子抑制剂 给药 口服 静脉输注，每 4 周一次口服，每日一次 标签人群 — 成人12 岁及以上 依据试验 — III 期II 期 PROGRESS（n＝63） Pasatru 在 III 期同时显示了新发骨形成减少与疼痛 flare 显著减少，证据更完整；Atebrioz 则以口服和年龄下限换来一个差异化的位置。专家视角 ：这是"证据更硬"与"覆盖更广"的典型交换。三款药同场，值得争的其实不是谁更有效，而在于各自切走了哪一段人群。9 月这场入场，把一个三年内刚刚成型的赛道分成了三块。七、安全性与剂量：一条儿科尾巴 安慰剂对照期内，多数不良事件为轻至中度，未因不良事件导致停药或减量。标签带有胚胎-胎儿毒性警告——这在育龄人群用药里是一条硬约束。 PROGRESS 的第二个队列（<12 岁儿童）数据预计明年可读，支撑补充申请；Regeneron 也在计划儿童试验但尚未公布细节。注册知识库提示 ：胚胎-胎儿毒性警告 + 儿童队列未完成，意味着这份标签是一个有缺口的状态。对引进方来说，管线价值不能只算已批适应症——应把"儿童队列能否在下一轮补上"当作独立的估值变量，同时评估该警告对育龄患者用药覆盖的实际影响。八、中国路径与全球同步 Atebrioz 由 Incyte 研发、Mirum 于 2026 年 4 月以 1600 万美元首付获得全球商业化权益（另有监管与销售里程碑）。本次批准同时向 Incyte 授予罕见儿科疾病优先审评券（PRV），且比其优先审评期限提前 1 天落地。 到 2026 年 9 月，未见 Atebrioz 已向 NMPA 递交上市申请的公开信息；亦未见企业公告或 CDE 受理公示。专家视角 ：PRV 是可以变现的资产，提前 1 天落地则说明审评队列排位很紧。对 License-in 方而言，这里有两个常被漏算的账：一是 PRV 的变现时点能否与上市首年产能爬坡对齐——拿到券却发不出货，等于白拿；二是儿童队列的读出节奏，它决定补充申请的窗口，也决定你从美国学到的"12 岁下限"在中国能不能原样平移。Mirum 预计 10 月上市并公布定价，分析师估计全球峰值销售约 1.5 亿美元——对一个全球不足千人的适应症，这是合理的量级。九、注册数据库速查 数据库 入口方 这次能帮查到什么ClinicalTrials.gov 美国国立医学图书馆 PROGRESS 的登记号、终点定义原文与状态变更；儿童队列的实际入组与预计读出月份FDA Drugs@FDA FDA Atebrioz 标签原文（剂量、胚胎-胎儿毒性警告措辞、_indication_ 限定语），用于判断美欧标签宽度CDE 药物临床试验登记与信息公示平台 国家药监局药审中心 中国是否已受理、拟纳入优先审评的情况 如果时间只够查一个，查 ClinicalTrials.gov——理由：PROGRESS 是这份标签的全部依据，而登记库里能看到试验方案与终点定义的原始版本，包括那个"未过线"的主要终点是怎么写的。企业新闻稿和媒体转述往往只挑 P＝0.004 那个数字说。十、解读边界 1. P＝0.0986 为预设主要终点的实际检验结果，未达统计学显著；−3.2 vs +24.6 cm³ 为名义 P 值（nominal），未作多重性校正。两者不可互相替代。 2. 上述数字来自不同终点、同一试验、同一人群；不构成统计学比较，只能作为效应方向的参考。 3. 第 48 周数据来自延伸期，含安慰剂交叉者，不是双盲对照数据，不能据此推断长期疗效。 4. Mirum 的定价、销售预测与儿童队列读出时间均为企业公开表述，非官方承诺。 5. 中国申报状态基于截至 2026 年 9 月 27 日的公开信息；未见公开信息不等于未申报。 可直接引用 · 数据卡 Atebrioz：2026-09-25 获批（FOP，12 岁及以上）｜PROGRESS Cohort 1，n＝63，双盲安慰剂对照 24 周｜预设主要终点 3.1% vs 16.7%，P＝0.0986 未过线｜FDA 采信终点 −3.2 cm³ vs +24.6 cm³，名义 P＝0.004｜剂量 100 mg QD｜全球 FOP 患者约 900 例。 适用场景：罕见病注册终点选择、小样本试验设计评估、License-in 品种估值材料可直接落笔引用。 行动项卡 · 如果你是注册人 ① 复查：在研罕见病项目的主要终点，在 n 很小时是否仍依赖比例型终点② 预设：若计划改采连续型终点，须在方案定稿时写成主要终点，不能事后换③ 跟踪：PROGRESS 儿童队列读出月份，作为补充申请排产的输入④ 评估：License-in 报价时把 PRV 变现时点与产能爬坡合并测算 关注「北京必诺达 · 注册科学观察」国内最专业的医药注册公众号 · 全球视野，科学客观 每期从全球主要监管机构与临床一线筛选真正值得注册人花时间的事，欢迎转发给同行。觉得有用请点「收藏」，需要时回看。 在公众号对话框回复「提问」，可提交你想让我们拆解的品种或事件。 本栏目由北京必诺达生物医药科技有限公司注册科学团队整理，仅供医药专业人士参考，不构成诊疗或投资意见。 ---