Lurasidone/Cycloserine

摘要：2025 年末，FDA 进入新药审批密集期，12 月下旬至年底将对 7 款重点药物作出关键裁决，覆盖哮喘、干眼症、罕见肥胖、库欣综合征等多个治疗领域。其中既有 GSK 超长效抗体的双适应症冲刺，也有 Aldeyra 三度闯关的干眼症药，更不乏 Vanda 争议药物的二次博弈，这场 “年终大考” 将改写多款疾病的治疗格局。GSK 双适应症同步闯关，半年给药成核心卖点 12 月 16 日，FDA 将率先对 GSK 的抗 IL-5 抗体 depemokimab 作出裁决，该药同时瞄准哮喘和慢性鼻-鼻窦炎伴鼻息肉（CRSwNP）两大适应症。 这款超长效生物药通过靶向 IL-5 细胞因子发挥抗炎作用，临床试验表现亮眼。在哮喘的 SWIFT-1 和 SWIFT-2 试验中，它较安慰剂使病情恶化年发生率降低 48% 至 58%；在 CRSwNP 的 ANCHOR-1 和 ANCHOR-2 试验中，显著改善患者鼻息肉评分和鼻塞症状。若获批，它将成为首款每半年给药一次的同类药物，大幅提升患者用药便利性。Aldeyra 三度冲刺，干眼症药靠 chamber 试验翻盘 同样在 12 月 16 日前，Aldeyra 的干眼症候选药 reproxalap 将迎来 FDA 第三次审查结果。这款药物的上市之路充满波折，2023 年首次申请因 “未证实眼部症状疗效” 被拒，2025 年 4 月再次遭驳回，要求补充临床数据。 转机出现在今年 6 月，Aldeyra 与 FDA 达成协议，仅需补充一项干眼症 chamber 试验数据即可重新提交。该试验最终成功，7 月 FDA 受理了重新申请。此次能否 “三战告捷”，成为业界关注的焦点。罕见病与慢病齐发力，多款药物拓展治疗边界 12 月 20 日前，Rhythm Pharmaceuticals 将为 Imcivree 的新适应症 “后天性下丘脑肥胖” 闯关。这种罕见肥胖多由下丘脑损伤或解剖异常引发，因 MC4R 信号紊乱导致食欲失控。III 期 TRANSCEND 研究显示，该药较安慰剂使患者 BMI 显著降低 19.8%。 Imcivree 已获批用于多种罕见肥胖，此次若拓展成功，将惠及更多患者。而 12 月 30 日前，Corcept Therapeutics 的皮质醇调节剂 relacorilant 也将迎裁决，该药针对库欣综合征，通过靶向糖皮质激素受体改善高皮质醇症状，关键试验 GRACE 及后续延伸研究均提供了有力数据支持。Vanda 争议药终局将至，一年拉锯战盼结果 12 月 30 日，Vanda Pharmaceuticals 的胃轻瘫药物 tradipitant 将迎来 FDA 的二次裁决。这款药物去年 9 月首次被拒后，引发企业与 FDA 的公开争执。Vanda 指责 FDA “无视证据”，FDA 则回应称其晚期试验 “未显示统计学显著疗效”。 双方矛盾持续升级，Vanda 曾向 FDA 前局长投诉，批评机构 “决策不透明”，直至 10 月才达成协作框架。此次裁决将为这场持续一年的拉锯战画上句号。年终收官战： bipolar 抑郁新药瞄准高危人群 2025 年最后一天前，NRx Pharmaceuticals 的 NRX-101 将接受审批，该药用于有静坐不能风险的双相抑郁患者。作为 D - 环丝氨酸与鲁拉西酮的固定剂量组合，其 IIb/III 期数据显示，可降低 33% 的自杀风险和 70% 的静坐不能症状。若获批，它将成为首款针对该类高危患者的治疗方案。 参考来源：https://www.biospace.com/fda/fdas-conundrum-what-to-do-with-approved-drugs-that-fail-pivotal-or-confirmatory-trials 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。

Taylor Tieden for BioSpace Coming up in the back half of December, the FDA will issue a verdict on Vanda Pharmaceuticals’ gastroparesis drug tradipitant, which it rejected last September, triggering a very public dispute with the company. The FDA will hand out seven big decisions before the year ends, including one for a rare form of obesity and two for an anti-inflammatory antibody. Read below for more. Dual Decisions for GSK’s Anti-IL-5 Antibody Kicking off the second half of December are back-to-back decisions for GSK, which is proposing its ultra-long-acting antibody depemokimab for the treatment of asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). The FDA’s verdicts are due Dec. 16. Depemokimab is designed to target the IL-5 cytokine, a known player in immune-mediated and inflammatory diseases. This mechanism of action enabled the biologic to ace both the SWIFT-1 and SWIFT-2 trials in asthma, significantly reducing the annualized rate of exacerbations by 48% to 58% as compared with placebo. Similarly, depemokimab aced the ANCHOR-1 and ANCHOR-2 trials in CRSwNP, leading to significant improvements in nasal polyp score and nasal obstructions. If approved, depemokimab would become the first ultra-long-acting biologic available for dosing every six months, according to GSK. Will Third Time Be the Charm for Aldeyra’s Dry Eye Disease Drug? On or before Dec. 16, the FDA is expected to release its decision on Aldeyra Therapeutics’ dry eye disease candidate reproxalap—concluding the agency’s third review of the drug. Aldeyra has been trying to get reproxalap across the regulatory finish line since 2023, when the FDA first swatted it back , citing the company’s failure to establish the drug’s “efficacy in treating ocular symptoms” in dry eye disease. Another rejection came in April this year, with the regulator asking for at least one more study to show reproxalap’s clinical benefit. In June, Aldeyra refiled its application for reproxalap, saying it had reached an agreement with the FDA where the only new clinical data required could come from a dry eye chamber trial, which was successful . The regulator accepted the resubmission in July. Rhythm Seeks Expansion for Rare Obesity Drug Rhythm Pharmaceuticals is proposing to use its subcutaneous melanocortin 4 receptor (MC4R) agonist Imcivree for the treatment of acquired hypothalamic obesity. The FDA is set to release a decision by Dec. 20. Acquired hypothalamic obesity is a rare form of the chronic disease that typically develops in patients who sustain physical injuries, or due to certain anatomical abnormalities of the hypothalamus. This condition is characterized by the disruption of MC4R signaling, leading to dysregulated hunger, energy expenditure and difficulty regulating weight. Rhythm is backing Imcivree’s expansion bid with data from the Phase III TRANSCEND study, which showed a statistically significant 19.8% placebo-adjusted reduction in body mass index in patients given the drug. Imcivree was first approved in late 2020 for chronic weight management in patients with obesity attributed to POMC, PCSK1 or LEPR deficiency. The drug has since also been cleared for Bardet-Biedl syndrome and expanded for use in patients as young as two years of age. Decision Day Nears for Vanda’s Gastroparesis Drug After Rejection, Public Spat After the FDA rejected Vanda Pharmaceuticals’ tradipitant for gastroparesis in September 2024, the Washington-based company very publicly blasted the decision, arguing that the regulator “generally disregarded the evidence provided.” Now, after more than a year of back-and-forth, the FDA is once again set to release a verdict on tradipitant by Dec. 30. Tradipitant is supported by several clinical efficacy trials, plus a 12-week open-label study, non-animal preclinical trials and Vanda’s expanded access program. In January, however, the FDA in an unusual step revealed its reasoning for the rejection, including that one late-stage trial that “did not demonstrate a statistically significant” treatment benefit. The spat between Vanda and the regulator has only become more convoluted—not to mention highly public. The company in January escalated its complaint to former FDA Commissioner Robert Califf, accusing the agency of what it called a “culture of obfuscation and closemindedness.” In April, Vanda again publicly blasted the agency , pointing to “FDA bureaucrats” who “have created policies to avoid scrutiny of their decision-making by habitually denying hearings.” Vanda and the FDA came to a “ collaborative framework ” in October to resolve its disputes. Corcept Eyes Approval for Cortisol Modulator Also by Dec. 30, the FDA is expected to release its decision on Corcept Therapeutics’ relacorilant, an investigational cortisol modulator for the treatment of Cushing’s syndrome. Also known as endogenous hypercortisolism, Cushing’s syndrome develops when the body produces an excess of the cortisol hormone. The disease manifests as a wide variety of syndromes, including hypertension, excessive body hair, easy bruising, fatigue and diabetes, among other symptoms. If left unchecked, Cushing’s syndrome can lead to many different complications, including infections, heart attack and memory problems. Relacorilant addresses Cushing’s syndrome by selectively targeting the glucocorticoid receptor. Data from the pivotal GRACE study showed that relacorilant improved various hypercortisolism symptoms. Corcept also supported its application with confirmatory evidence from the late-stage GRADIENT study, a long-term extension study and a Phase II trial. NRx To Close 2025 With Bipolar Depression Verdict Closing out this list—and the year—is NRx Pharmaceuticals, which is proposing NRX-101 for the treatment of bipolar depression in patients who are at risk of akathisia, a movement disorder that causes a feeling of restlessness. The regulatory review for this drug is ongoing and a decision is expected “prior to December 31, 2025,” according to the company’s 2024 annual report filed in March. NRX-101 is a fixed-dose combination of the NMDA receptor modulator D-cycloserine and the 5-HT2a receptor blocker lurasidone, both of which have separately been approved by the FDA for different indications. Phase IIb/III data showed that NRX-101 cut suicidality by 33% and symptoms of akathisia—a common side effect of antidepressant therapies also associated with suicidality—by 70%. These effects were not statistically significant. If approved, NRX-101 would become the first drug regimen for severe bipolar depression in patients suffering from both acute and sub-acute suicidal ideation or behavior, according to NRx’s website .