Ponesimod

摘要：2025 年末，美国 FDA 接连批准两款重要新药：12 月 23 日核准 Agios 制药的口服药物 Aqvesme 用于治疗成人α或β地中海贫血相关贫血，12 月 30 日又为 Vanda 制药的晕车药 Nereus 亮绿灯。这两项审批均历经波折，却为特定患者群体带来新希望，也成为 FDA 年度监管工作的收官亮点。地中海贫血治疗突破：Aqvesme 减轻患者输血负担 Agios 制药的 Aqvesme（活性成分 mitapivat）获批之路并不顺畅。FDA 最初将审批日期从 9 月 7 日推迟至 12 月 7 日，需额外时间审查其风险评估与缓解策略（REMS），以应对潜在肝损伤风险。12 月初，因需完善 REMS 计划的标签文件，审批再次延后。 这是 mitapivat 获得的第二项 FDA 批准。四年多前，该药物以 Pyrukynd 为商品名获批，用于治疗罕见遗传病丙酮酸激酶缺乏症引发的溶血性贫血。此次获批使适用人群大幅扩大，涵盖输血依赖型和非输血依赖型α或β地中海贫血成人患者。 Agios 首席执行官布莱恩・戈夫在圣诞夜电话会议中表示，Aqvesme 让患者摆脱了输血或皮下注射治疗的负担，也是首个能改善非输血依赖型患者生活质量的药物。该药将于 1 月底 REMS 计划实施后上市，年供应价 42.5 万美元，高于 Pyrukynd 的 33.5 万美元批发采购价。 值得注意的是，Aqvesme 标签包含肝细胞损伤的黑框警告，患者用药前需接受肝功能检测，用药后 24 周内每四周检测一次。Agios 称，单独设立商品名可使 Aqvesme 的 REMS 计划仅适用于地中海贫血患者，避免与 Pyrukynd 的监管要求混淆。2025 年前三季度，Pyrukynd 销售额达 3400 万美元，三季度用药患者 149 人。四十载新突破：Nereus 成晕车治疗新选择 Vanda 制药的 Nereus（活性成分 tradipitant）则结束了晕车治疗四十余年无新药理疗法的局面。这款口服神经激肽-1（NK-1）受体拮抗剂的获批，距其因胃轻瘫适应症被 FDA 拒绝仅过去 15 个月。 此前的完整回应函曾引发 Vanda 强烈不满，该公司抨击 FDA 延迟决策且未召开咨询委员会会议讨论药物价值。此次转机源于 12 月 4 日 FDA 解除部分临床暂停，认定晕车并非慢性疾病，Nereus 属于 "急性、事件驱动型疗法"，无需进行六个月的毒性研究。 三项 III期临床试验为获批提供了有力支持，其中两项在船上开展。在一项 365 人参与的船载研究中，服用 Nereus 的患者呕吐发生率为 19%，而安慰剂组达 44%，该药对有晕车史患者的恶心症状也有改善作用。 Nereus将于未来数月上市，成为 Vanda 旗下第四款获批药物。该公司现有精神分裂症治疗药物 Fanapt（2024 年扩展用于双相 I 型障碍）、睡眠障碍药物 Hetlioz 和复发型多发性硬化症治疗药物 Ponvory。2025 年前三季度，Fanapt 销售额达 8400 万美元，同比增长 24%。 Vanda 并未放弃 tradipitant 的胃轻瘫适应症申请，同时正研究其用于预防 GLP-1 类减肥药引发的恶心呕吐。此外，FDA 将于1月7日决定是否批准 Hetlioz 用于时差反应障碍治疗。参考来源：https://www.fiercepharma.com/pharma/vandas-motion-sickness-drug-and-agios-thalassemia-treatment-make-grade-fda 识别微信二维码，可添加药时空小编 请注明：姓名+研究方向！

Over the holidays, the FDA gave thumbs up to Vanda Pharmaceuticals' motion sickness pill Nereus and to Agios Pharmaceuticals' thalassemia treatment Aqvesme. The FDA delivered a pair of holiday season approvals a week apart, signing off on Agios’ oral medicine Aqvesme for the treatment of anemia in adults with alpha- or beta-thalassemia on Dec. 23, and then issuing its final new drug approval of the year to Vanda Pharmaceuticals for motion sickness pill Nereus on Dec. 30.As has been the case with many FDA decisions in this year of cutbacks and leadership transition, neither nod was accomplished easily.The endorsement for Agios came after the FDA shifted its decision date from Sept. 7 to Dec. 7, needing additional time to review the company’s Risk Evaluation and Mitigation Strategy (REMS) to mitigate potential liver injury that comes with the use of Aqvesme (mitapivat). Then, in early December, the company explained that there was another decision delay as it was working with the agency to “finalize the labeling documents” for its REMS plan.As for Vanda, its approval arrived after the FDA lifted a partial clinical hold on Dec. 4, concluding that motion sickness is not a chronic condition and that Nereus (tradipitant) is an “acute, event-driven therapy.” With that, the U.S. regulator determined that a six-month toxicity study of tradipitant was not necessary. Agios’ 2nd nod for mitapivatThis is not Agios’ first go-round with the FDA on mitapivat. Nearly four years ago, the agency blessed it with the commercial name Pyrukynd as the first treatment to reduce hemolytic anemia in adults with the rare, genetic blood disorder pyruvate kinase (PK) deficiency.The endorsement for twice-daily Aqvesme opens the treatment up to a larger patient population, including those with non-transfusion-dependent or transfusion-dependent alpha- or beta-thalassemia. It relieves patients from the burden of transfusions or subcutaneous treatments. It is also the “first medicine to show quality of life improvements in non-transfusion-dependent patients, which we understand to be of critical importance,” Agios CEO Brian Goff said in a Christmas Eve conference call. The company will make Aqvesme available in late January after its REMS program is implemented, Agios said. It will charge $425,000 for a yearly supply of Aqvesme, which is up from the $335,000 wholesale acquisition cost of Pyrukynd. The separate brand names for mitapivat allows Agios to “isolate the Aqvesme REMS to thalassemia, ensuring regulatory clarity and confirming that it does not apply to Pyrukynd for PK deficiency,” Goff added.The label of Aqvesme will include a boxed warning for hepatocellular injury. The REMS program will require patients to undergo liver testing before beginning treatment and then every four weeks of the next 24 weeks after initiating its use.Agios reported sales of Pyrukynd reached $34 million for the first three quarters of 2025, with 149 patients on therapy in the third quarter, up from 136 in the first quarter. The company estimates the addressable thalassemia patient population at 4,000 in the U.S. Vanda scores with NereusThe FDA motion sickness blessing for Nereus comes 15 months after the FDA rejected the oral neurokinin-1 (NK-1) receptor antagonist to reduce nausea and vomiting in patients with the digestive disorder gastroparesis.The complete response letter (CRL) triggered a fiery response from the Washington, D.C.-based drugmaker, which blasted the agency for the delay in its decision and for not conducting an advisory committee meeting to discuss the treatment's value.  Nereus made the grade, however, as the FDA blessed it to reduce the incidence of motion-induced vomiting. With the nod, Nereus has become the first new pharmacologic treatment for the condition in more than four decades, the drugmaker said.The approval was backed by three phase 3 trials, including two conducted on boats, which showed that it reduced nausea in participants with a history of motion sickness. In one boat study of 365 participants, there was a 19% incidence of vomiting of those on Nereus compared to a 44% incidence for those on placebo. Vanda said it will make Nereus available in the “coming months.” It becomes the fourth drug on the market for Vanda, which scored a 2009 approval for schizophrenia treatment Fanapt, followed by a 2024 expansion to treat bipolar I disorder. The new indication helped Vanda boost sales of Fanapt to $84 million over the first nine months of 2025, a 24% year-over-year increase.Vanda also sells sleep disorder drug Hetlioz, which reached the market in 2014, and relapsing multiple sclerosis treatment Ponvory, which was approved in 2021. The FDA is scheduled on Jan. 7 to decide on Vanda’s Hetlioz as a treatment for jet lag disorder.As for tradipitant, Vanda hasn’t surrendered its effort to get it across the FDA finish line for gastroparesis. Vanda also is studying tradipitant to prevent nausea and vomiting induced by GLP-1 obesity drugs.