Santhera Pharmaceuticals (USA), Inc.

12月18日，Santhera Pharmaceuticals（SIX：SANN）宣布，AGAMREE®（vamorolone）已在欧盟（EU）获批，用于治疗4岁及以上患者的杜氏肌营养不良症（DMD）。杜氏肌营养不良症(Duchenne muscular dystrophy，DMD)是一种严重的进行性肌肉萎缩性疾病，发病后患者运动困难，严重时需要辅助呼吸并最终导致过早死亡。AGAMREE®（vamorolone）是一种新型“first-in-class”类固醇药物，与泼尼松等普通皮质类固醇药物不同，Vamorolone能够选择性地激活类固醇的某些信号通路，在保持类固醇对DMD抗炎症疗效的同时减少副作用的产生。此次EC的批准基于 VISION-DMD 研究和三项开放标签研究积极的关键数据。欧洲药品管理局（EMA）表示，与标准治疗皮质类固醇相比，AGAMREE在维持正常的骨代谢、密度和生长方面具有重要的临床安全性，且疗效相似。此外，从标准护理皮质类固醇转换为AGAMREE的患者在恢复生长和骨骼健康的同时保持了疗效益处。DMD药物各国上市进程FDA2023年6月22日，FDA批准了由Sarepta Therapeutics公司与Roche联合开发的基因疗法药物Elevidys（delandistrogene moxeparvovec，SRP-9001），用于治疗4-5岁的DMD患者。Elevidys是首个获批的以AAVrh74病毒为载体的DMD基因疗法。10⽉27⽇，Santhera宣布，FDA在美国批准AGAMREE⼝服混悬液40mg/ml⽤于治疗2岁及以上DMD患者。该药成为首个获完全批准（而非附条件上市）的 DMD 新药。中国2022年1月4日，中国罕见病新药研发与商业化创新型企业曙方医药与瑞士Santhera制药宣布就罕见病新药Vamorolone达成独家授权协议，曙方医药获得在大中华区开发和商业化Vamorolone用于杜氏肌营养不良（DMD）及其他罕见病适应症的独家权益，协议总金额达1.24亿美元。7月15日，Vamorolone 口服混悬液获得CDE默示许可（受理号为：JXHL2300093），允许其在华开展桥接试验。9月16日，CDE官网表明：曙方医药联合Santhera制药申报的新药vamorolone被纳入“突破性治疗药物”程序，拟定适应症为2岁及以上的杜氏肌营养不良（DMD）患者。年初时曙方医药曾透露，vamorolone在国内的最早预计上市时间在2024年。往期推荐恒瑞医药生物药管线全梳理中生制药企业梳理石药集团生物药技术平台及管线梳理国内ADC热门靶点竞争格局一览点击下方“药研网”，关注更多精彩内容

Ad hoc announcement pursuant to Art. 53 LR Food and Drug Administration (FDA) approved AGAMREE® (vamorolone) for the treatment of Duchenne muscular dystrophy (DMD) in children and adults aged 2 years and older U.S. license holder Catalyst Pharmaceuticals plans for commercial launch in Q1-2024 FDA approval triggers USD 36 million payment obligation from Catalyst to Santhera, of which USD 26 million will be used to cover Santhera’s third-party milestone obligations Following the recent positive CHMP opinion on AGAMREE in DMD, approval in the European Union by the European Commission (EC) is expected in late 2023 AGAMREE would then become the first drug fully approved in both the U.S. and Europe for the treatment of patients with DMD Santhera Pharmaceuticals (SIX: SANN) announces that the U.S. Food and Drug Administration (FDA) has approved AGAMREE® (vamorolone) oral suspension 40 mg/ml for the treatment of Duchenne muscular dystrophy (DMD) in patients 2 years of age and older. “We are delighted to secure FDA approval which comes just weeks after the positive opinion from the CHMP of the European Medicines Agency. This is a hugely important moment for DMD patients who need an efficacious and well-tolerated therapy for this debilitating condition,” said Dario Eklund, CEO of Santhera. “Today is a very satisfying day for the Santhera team and we are grateful to the patients, their families and physicians who participated in the vamorolone program. We look forward to working closely with our partner Catalyst Pharmaceuticals as it prepares for U.S. commercialization of the product.” “This new drug approval gives Duchenne patients and their families one more reason for hope,” said Pat Furlong, Founding President & CEO Parent Project Muscular Dystrophy (PPMD). “Steroids are considered standard of care for Duchenne, due to their valuable role in slowing disease progression. However, they often come with considerable side effects. Vamorolone has the potential to be an alternative steroid with a better tolerability profile addressing an important unmet medical need for patients.” “I am excited for the Duchenne community who have been waiting a long time for an alternative to the current standard of care. Today’s news represents the culmination of many years of research to bring vamorolone to patients,” said Eric Hoffman, PhD, President and CEO of ReveraGen BioPharma. “We are pleased to have worked alongside Santhera, the DMD patient community, researchers and healthcare practitioners to reach this important milestone.” The FDA approval of AGAMREE® was based on the data from the pivotal Phase 2b VISION-DMD study as supplemented with safety information collected from three open-label studies, including extension studies. In these trials, AGAMREE was administered at doses ranging from 2 to 6 mg/kg/day, extending for a period of up to 48 months. Compared with current standard of care corticosteroids, this novel corticosteroid treatment exhibited comparable efficacy, with data suggesting a reduction in adverse events, notably related to bone health, growth trajectory and behavior. The studies in the development program were carried out by Santhera’s partner ReveraGen and 32 academic clinical trial centers in 11 countries. With the FDA approval of AGAMREE for DMD, Catalyst will pay USD 36 million to Santhera, consisting of a USD 10 million approval milestone to the Company and an additional USD 26 million to cover contracted third-party milestone obligations. Furthermore, under the terms of the agreement, Catalyst will pay Santhera sales-based milestones of up to USD 105 million as well as up to low-teen percentage royalties, and will assume Santhera's corresponding third-party royalty obligations on vamorolone sales in all indications in North America. Santhera will now transfer the U.S. marketing authorization (NDA) for AGAMREE to its partner Catalyst Pharmaceuticals who holds an exclusive license for AGAMREE in North America and plans to launch the product in the U.S. in Q1-2024. In Europe, following the positive opinion from the CHMP received on October 12, 2023, approval of AGAMREE (vamorolone) for the treatment of DMD by the European Commission is expected in late 2023. Subject to approval, AGAMREE will be the only medicinal product fully approved in both territories, the EU and the U.S., for the treatment of DMD. Vamorolone is a novel drug candidate with a mode of action based on binding to the same receptor as glucocorticoids but modifying its downstream activity and is not a substrate for the 11-β-hydroxysteroid dehydrogenase (11β-HSD) enzymes that may be responsible for local tissue amplification and corticosteroid-associated toxicity in local tissues [1-3]. This mechanism has shown the potential to ‘dissociate’ efficacy from steroid safety concerns and therefore vamorolone is positioned as an alternative to existing corticosteroids, the current standard of care in children and adolescent patients with DMD [1-3]. In the pivotal VISION-DMD study, vamorolone met the primary endpoint Time to Stand (TTSTAND) velocity versus placebo (p=0.002) at 24 weeks of treatment and showed a good safety and tolerability profile [1]. The most commonly reported adverse events versus placebo from the VISION-DMD study were cushingoid features, vomiting and vitamin D deficiency. Adverse events were generally of mild to moderate severity. Currently available data show that vamorolone, unlike corticosteroids, has no restriction of growth [4] and no negative effects on bone metabolism as demonstrated by normal bone formation and bone resorption serum markers [5]. AGAMREE (vamorolone) has Orphan Drug status for DMD in the U.S. and in Europe and has received Fast Track and Rare Pediatric Disease designations by the U.S. FDA and Promising Innovative Medicine (PIM) status from the UK MHRA for DMD. Vamorolone is not approved for use outside the United States. References: [1] Guglieri M et al (2022). JAMA Neurol. 2022;79(10):1005-1014. doi:10.1001/jamaneurol.2022.2480. Link. [2] Liu X et al (2020). Proc Natl Acad Sci USA 117:24285-24293 [3] Heier CR et al (2019). Life Science Alliance DOI: 10.26508 [4] Ward et al., WMS 2022, FP.27 - Poster 71. Link. [5] Hasham et al., MDA 2022 Poster presentation. Link. Duchenne muscular dystrophy (DMD) is a rare inherited X-chromosome-linked disease, which almost exclusively affects males. DMD is characterized by inflammation which is present at birth or shortly thereafter. Inflammation leads to fibrosis of muscle and is clinically manifested by progressive muscle degeneration and weakness. Major milestones in the disease are the loss of ambulation, the loss of self-feeding, the start of assisted ventilation, and the development of cardiomyopathy. DMD reduces life expectancy to before the fourth decade due to respiratory and/or cardiac failure. Corticosteroids are the current standard of care for the treatment of DMD. Santhera Pharmaceuticals (SIX: SANN) is a Swiss specialty pharmaceutical company focused on the development and commercialization of innovative medicines for rare neuromuscular and pulmonary diseases with high unmet medical need. The Company has an exclusive license from ReveraGen for all indications worldwide to AGAMREE® (vamorolone), a dissociative steroid with novel mode of action, which was investigated in a pivotal study in patients with Duchenne muscular dystrophy (DMD) as an alternative to standard corticosteroids. AGAMREE for the treatment of DMD is approved by the U.S. Food and Drug Administration (FDA); in Europe, the marketing authorization application (MAA) has received a positive opinion from the European Medicines Agency’s CHMP in October 2023, and is under review by the UK Medicines and Healthcare products Regulatory Agency (MHRA). Santhera has out-licensed rights to vamorolone for North America to Catalyst Pharmaceuticals and for China to Sperogenix Therapeutics. The clinical stage pipeline also includes lonodelestat to treat cystic fibrosis (CF) and other neutrophilic pulmonary diseases. For further information, please visit www.santhera.com. The content above comes from the network. if any infringement, please contact us to modify.

今日，由Santhera Pharmaceuticals与ReveraGen BioPharma公司联合开发、用于治疗杜氏肌营养不良症（DMD）的创新疗法Agamree（vamorolone）获得美国FDA批准上市，用于治疗2岁及以上的DMD患者。 DMD是最常见的儿童神经肌肉疾病之一。它是由于在X染色体上编码抗肌萎缩蛋白（dystrophin）的基因出现突变而导致的X连锁遗传病。抗肌萎缩蛋白的缺失最终导致肌纤维退化，组织纤维化和早夭。接近50%的患者每天使用糖皮质激素。这些激素虽然可以延缓疾病进展，但具有很多副作用。 Vamorolone是最初由ReveraGen Biopharma公司研发的类固醇药物。它与普通类固醇药物的区别在于，能够有选择性地激活类固醇的某些信号通路。在DMD患者中，类固醇药物的抗炎症效果是介导药物疗效的主要机制，但是类固醇的其它活性会带来影响患者生活质量的副作用。Vamorolone能够在保持类固醇对DMD疗效的同时减少副作用的产生。Vamorolone获得美国与欧洲用以治疗DMD的孤儿药资格，并获得美国FDA快速通道资格与罕见儿科疾病认定。Santhera已将vamorolone在北美与中国的权益分别授权给Catalyst Pharmaceuticals与曙方医药（Sperogenix Therapeutics）。 这次申请递交主要基于来自VISION-DMD关键临床2b期试验的积极结果，该试验检视与安慰剂和强的松（prednisone，0.75 mg/kg/day）相比，vamorolone（2-6 mg/kg/day）治疗DMD患者的疗效与安全性。 分析显示，试验达到主要终点，试验组患者在治疗24周后由卧位至站立所需时间（TTSTAND，DMD儿童患者疾病恶化的一项功能性指标）优于安慰剂组，且差异有统计学意义（p=0.002）。 此外，与皮质类固醇不同，在临床研究中，48周后，通过骨生物标志物测量，vamorolone未导致患者的骨代谢降低，通过双能X线吸收测量法（DXA）测量时，也未发现该药物导致脊柱骨矿化显著减少。 在VISION-DMD试验中，与安慰剂相比，最常报告的不良事件为库欣样特征、呕吐和维生素D缺乏。不良事件的严重程度通常为轻度至中度。 参考资料：[1] Catalyst Pharmaceuticals Reports FDA Approval of AGAMREE® (vamorolone) for Duchenne Muscular Dystrophy Granted to Santhera Pharmaceuticals. Retrieved October 26, 2023 from https://ir.catalystpharma.com/news-releases/news-release-details/catalyst-pharmaceuticals-reports-fda-approval-agamreer 内容来源于网络，如有侵权，请联系删除。