CDKL5 Deficiency Disorder

Today, a brief rundown of news from GSK and Amgen, as well as updates from Roche, AbbVie, and Marinus Pharmaceuticals that you may have missed.Amgen set a list price of $1,665 per shot for its biosimilar version of Regenerons Eylea, a 10% discount from the eye drugs current wholesale cost, RBC analyst Brian Abrahams wrote in an Oct. 25 note to clients. On Tuesday, Amgen said it would launch its biosimilar, branded Pavblu, without a legal settlement with Regeneron following a court decision that lifted a temporary injunction on its launch. Such at risk launches are uncommon, and could result in steep penalties for Amgen if subsequent legal judgments side with Regeneron. The small discount means the market impact of Pavblu may be more muted than Amgen investors feared, Abrahams wrote. Further price erosion could occur when additional biosimilars launch. The FDA has approved four others. Jonathan GardnerGSK is making its largest investment in U.S. manufacturing, committing $800 million to expand a site in Marietta, Pennsylvania with new drugmaking facilities. One will handle production of sterile liquid vaccines and medicines, and should be ready by the end of 2028. Another will include a drug substance facility set to start operations by the end of 2027 as well as a pilot plant for making clinical trial medicines. Ned PagliaruloRoche has inked a second research collaboration with gene therapy specialist Dyno Therapeutics. The companies originally linked up in 2020 and, similar to that deal, the one announced Thursday revolves around neurological diseases. Roche and Dyno think the latter's technology can be used to create better “viral vectors“ the microscopic tools that shuttle genetic medicines to a desired target. The new deal tasks Dyno with designing these improved vectors, which will then be applied to potential gene therapies for nervous system disorders. Roche will be responsible for testing the therapies and, if they make it to the market, selling them. Dyno is getting $50 million upfront, plus research payments. It's also eligible for royalties on resulting products, and could nab north of $1 billion more by hitting certain milestones. Jacob BellLongtime partners AbbVie and Gideon Richter are working together on another brain-focused project. Through a sparsely detailed agreement announced Thursday, the companies hope to discover new targets that could be used to treat neuropsychiatric conditions. They plan to share the costs of the necessary research and development. Richter will receive $25 million upfront, and could take home more through milestone and royalty payments. AbbVie, meanwhile, will get worldwide rights to programs that advance to commercialization, except in traditional markets of Richter, such as Europe and Russia. Jacob BellMarinus Pharmaceuticals will lay off staff, cut costs and consider strategic alternatives, after results from a Phase 3 study showed the companys seizure drug ganaxolone did not meet the trials goal. On Thursday, Marinus said the data, while finding nominal reductions in seizure frequency that favored ganaxolone, were likely not enough to support an approval application. The study tested ganaxolone in people with epilepsy related to tuberous sclerosis complex; the drug is already cleared for use treating seizures in people with a condition called CDKL5 deficiency disorder. Ned Pagliarulo '

Marinus Pharmaceuticals is reducing its workforce again and taking other measures to reduce costs after its epilepsy treatment failed a late-stage trial. The TrustTSC trial investigating oral ganaxolone for the treatment of seizures associated with tuberous sclerosis complex (TSC) missed the primary endpoint of percent change in TSC-associated frequency of seizures at 28 days. While there was a reduction in seizures in the treatment arm, the results weren’t statistically significant. The median reduction in seizure frequency was 19.7% for patients on ganaxolone compared with 10.2% for placebo, earning a p-value of 0.09. The company’s stock $MRNS tumbled on Thursday morning, dropping about 80%. “We are disappointed that the results of the TrustTSC trial are not likely to be sufficient for an sNDA filing,” Marinus CEO Scott Braunstein said in a statement . Marinus now plans to discontinue all clinical development of ganaxolone, and it started a “strategic alternatives” process that includes layoffs. The company didn’t specify how many employees it would let go. As of Dec. 31, Marinus had 165 full-time employees, though it cut about 20% of its workforce in May when it also implemented other cost-reducing measures. Since 2022, ganaxolone has been approved as Ztalmy for the treatment of seizures associated with CDKL5 deficiency disorder.

Insight 数据库「医药交易」模块显示，本周全球范围内共发生 13 项医药交易（截至 10 月 18 日），涉及辉瑞、诺华、赛诺菲、百裕制药、灵北制药、晖致医药等公司。 其中： 大额交易中，有灵北制药约 25 亿美元收购罕见病公司获得癫痫新药，辉瑞超 15 亿美元布局分子胶降解剂； 在中国创新药出海方面，百裕制药开发的一款小分子抗肿瘤药以 11.7 亿美元的价格授予诺华； 另外，还有赛诺菲、灵北制药、晖致医药等公司达成新合作，涉及放射性配体疗法、SGLT-1/2 双效抑制剂、5-HT2C 受体激动剂、YKL-40 抑制剂等创新产品。 下面，Insight 数据库将节选部分备受关注的交易案例做介绍，仅供读者参阅。 跨国药企竞相布局新疗法   辉瑞超 15 亿美元布局分子胶 TRIANA Biomedicines 与辉瑞达成合作，以发现包括肿瘤学在内多个疾病领域多个靶点的新型分子胶降解剂。为此，前者将获得 4900 万美元预付款，并有资格获得超过 15 亿美元的潜在未来里程碑以及分层特许权使用费。 根据协议，TRIANA 公司将利用其分子胶发现平台，领导发现和确定潜在的开发候选管线。而辉瑞将拥有独家许可选择权，以进一步推进临床前和临床开发。   诺华约 11.7 亿美元引进百裕制药小分子抗肿瘤药 诺华与百裕制药签订独家许可协议，获得百裕制药一款在研抗肿瘤小分子药物的全球独家开发及商业化权利。根据协议，百裕制药将收到 7000 万美元首付款，及可达 11 亿美元的开发、注册、商业化等里程碑付款和相应特许权使用费。 百裕制药专注银杏核心药效成分研究二十余年，聚焦肿瘤及自身免疫疾病领域。此次授权的产品正是该公司创新药团队发现的一款治疗恶性肿瘤小分子创新药。   赛诺菲 3 亿欧元股权投资 Orano Med 赛诺菲与 Orano Med 签署协议，加速下一代放射性配体药物的开发。根据协议，赛诺菲将向 Orano Med 进行 3 亿欧元的股权投资。基于 Orano Med 的专业知识及其放射性配体药物研发管线，双方将共同专注于基于铅-212 同位素的α粒子放射性配体疗法的发现、设计和临床开发。 上个月，赛诺菲已与 RadioMedix 和 Orano Med 达成总额约 3.2 亿欧元合作，以共同开发基于同位素铅的放射性配体疗法（RLT）用于癌症治疗。该合作则主要聚焦于后期临床项目 AlphaMedix，用于治疗进展性生长抑素受体表达神经内分泌肿瘤（NET）成年患者。 其它授权合作   灵北制药收购公司获得癫痫新药 灵北制药（Lundbeck）和 Longboard Pharmaceuticals 达成协议，灵北制药将收购 Longboard 公司并获得潜在「best-in-class」产品 bexicaserin（LP352）。该交易预计将于 2024 年第四季度完成，总交易价值约为 26 亿美元股权价值和 25 亿美元现金净额。 Bexicaserin 是一款高选择性、口服、新型 5-HT2C 受体激动剂，正在开发用于治疗与发育性癫痫性脑病（DEE）相关的癫痫发作，包括 Dravet 综合征、Lennox-Gastaut 综合征和其他罕见癫痫。目前，该产品用于治疗 Dravet 综合征相关癫痫发作的全球 3 期试验正在进行中。   晖致医药 2500 万美元引进 SGLT-1/2 双效抑制剂 晖致医药（Viatris）获得 Lexicon Pharmaceutical 独家许可，可在美国和欧洲以外的所有适应症中商业化 SGLT-1/2 双效抑制剂 Sotagliflozin，Lexicon 保留了该药在美国和欧洲所有适应症的独家商业化权利。为此，Lexicon 公司将获得 2500 万美元的预付款及潜在监管和商业里程碑付款。 Sotagliflozin 已于 2023 年 5 月获得美国 FDA 批准，用于降低成人患者的心血管死亡、因心力衰竭而住院或接受急救的风险。这些患者患有心力衰竭或 2 型糖尿病、慢性肾病，并携带其它心血管疾病风险因子。   Molecure 与 Ocean Biomedical 达成合作 Molecure 公司与 Ocean Biomedical 签署了一项独家许可协议，后者获得了在全球范围内进一步研究、开发、制造和商业化 Molecure 公司 OAT-3912 和其他选择性 YKL-40 抑制剂的独家权利。根据协议，Molecure 公司将获得 60 万美元的现金和股票作为初始补偿，并有望获得潜在里程碑付款，协议最高价值约为 3200 万美元。 该协议涵盖了「first-in-class」的小分子 YKL-40 抑制剂，包括先导分子 OAT-3912，它在各种癌症及炎症和纤维化疾病的临床前模型中显示出潜在治疗益处。   Orasis 公司 1800 万美元授出滴眼液韩国权益 Orasis Pharmaceuticals 授予 Optus pharmaceutical 在韩国商业化、进口和销售 0.4% Qlosi（盐酸匹罗卡品滴眼液）的权利，这是一种治疗成人老视的新型矫正滴眼液。 根据协议，这项合作其他条款包括预付款和关键里程碑的付款，共计 1800 万美元，此外还有韩国市场销售额的两位数特许权使用费。Optus 公司计划率先在韩国市场推出一种新的老视治疗药物，并计划在获得监管批准和销售批准后，于 2026 年在韩国推出 Qlosi。 除了上述案例，本周还有一些其它公司也达成了不同类型的合作，限于篇幅，此处不再一一介绍。欲了解本周更多授权合作信息，可点击阅读原文前往 Insight 数据库「医药交易」模块查看。 封面来源：站酷海洛 Plus 免责声明：本文仅作信息分享，不代表 Insight 立场和观点，也不作治疗方案推荐和介绍。如有需求，请咨询和联系正规医疗机构。 编辑：馨药 PR 稿对接：微信 insightxb 投稿：微信 insightxb；邮箱 insight@dxy.cn 多样化功能、可溯源数据…… Insight 数据库网页版等你体验 点击阅读原文，立刻解锁！