Congenital Disorders of Glycosylation

近日，Applied Therapeutics公布了其核心管线Govorestat新药申请(NDA)审查的积极消息。 FDA通知公司，不再需要召开专家咨询委员会会议（adcomm）来针对Govorestat进行讨论，该会议之前原定于2024年10月9日举行。 这一举动令Applied大松一口气，因为去年Govorestat未能通过一项III期临床（ACTION-Galactosemia ），并且上市申请审评期还在今年3月还被FDA延长三个月。 取消在adcom上对该药的投票表决，已经表明了监管态度。不用在adcomm中走一遭，Govorestat被上市通过的概率将大大提升。 FDA表示优先审查计划将如期进行，PDUFA目标行动日仍定在2024年11月28日。 受此消息鼓舞，公司股价上涨了近70%。 Govorestat是Applied Therapeutics最为核心的管线，如果获得批准，将成为Applied的首个商业产品。 Govorestat是一种具有中枢神经系统渗透性的醛糖还原酶抑制剂（ARI），被开发用于治疗多种罕见的神经系统疾病，包括半乳糖血症、山梨醇脱氢酶缺乏症（SORD）和磷酸甘露糖变位酶2-先天性糖基化障碍（PMM2-CDG）。 半乳糖血症是Govorestat首发适应症。如果Govorestat获得批准，将成为首个用于治疗半乳糖血症的药物。 2024年2月，govorestat治疗半乳糖血症的NDA获得了FDA受理，并获得了优先审评。 NDA申请得到了半乳糖醇快速和持续降低的支持，包括针对2-17岁半乳糖血症儿童的Ⅲ期临床数据ACTION-Galactosemia Kid、以及针对成人半乳糖血症患者的ACTION-GalactosemiaⅠ/Ⅱ期临床数据。 Applied亦向欧洲药品管理局（EMA）递交治疗半乳糖血症的上市许可申请(MAA)，目前正在接受EMA人用药品委员会(CHMP)的审查。公司预计EMA将在2024年第四季度做出审批决定。 此外，Govorestat在其他适应症中取得了临床积极结果。 今年2月，Applied 公布了Govorestat治疗SORD缺乏症的Ⅲ期临床INSPIRE试验12个月中期分析结果，该试验达到了主要终点和几个关键次要终点。 与安慰剂相比，Govorestat在山梨醇水平持续下降具有统计学意义。此外，govorestat在CMT健康指数（CMT-HI）方面也产生了显著的统计学意义，患者的下肢功能、活动能力、感觉功能和上肢功能的改善。安全性和耐受性良好，治疗组和安慰剂组的不良事件发生率相似。 基于迄今为止的临床数据，公司计划与FDA讨论针对该适应症的新药上市申请。 官网中还有有两条管线AT-001和AT-003，业均为醛糖还原酶抑制剂。AT-001已经推进到了临床Ⅲ期阶段，不过最近报告的消息看起来不算好，2024年1月4日，AT-001治疗糖尿病心肌病ARISE-HF的Ⅲ期临床中主要终点没有达到。 AT-003是一款具有眼球内的渗透性的ARI，目前还在临床前阶段，用于治疗糖尿病性视网膜病变。 从经营现状看来，Govorestat尽快取得上市批准也是十分急迫的了。 参考出处： https://firstwordpharma.com/story/5841711 https://ir.appliedtherapeutics.com/news-releases/news-release-details/applied-therapeutics-provides-regulatory-update-govorestat https://ir.appliedtherapeutics.com/static-files/2f5dd433-9a82-40b9-ae3f-3da06ce5bff8 本周好文推荐 如需转载请联系佰傲谷并在醒目位置注明出处 · · · · · · · ·

SAN CARLOS, Calif.--( BUSINESS WIRE )-- Glycomine, Inc. , a biotechnology company focused on developing new therapies for orphan diseases, announced today that the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation for GLM101, a mannose-1-phosphate replacement therapy in development for the treatment of patients with phosphomannomutase 2-congenital disorder of glycosylation (PMM2-CDG). “Fast Track Designation for GLM101 highlights its potential to meet the serious unmet medical need of patients with PMM2-CDG,” said Rose Marino, M.D., Chief Medical Officer of Glycomine. “As we continue to enroll pediatric patients in our Phase 2 clinical study, we are encouraged by our initial data showing promising evidence of clinical benefit with GLM101. We look forward to progressing development of GLM101 within the Fast Track framework.” The GLM101-002 Phase 2 clinical study has enrolled 10 adult and five adolescent patients with PMM2-CDG in the U.S. and Spain (ClinicalTrials.gov Identifier: NCT05549219). Study participants have completed treatment with GLM101 at either 10 mg/kg (n=3), 20 mg/kg (n=3), or 30 mg/kg (n=9) for up to 24 weeks. More than 350 doses of GLM101 have been administered to PMM2-CDG patients. The drug appears to be well tolerated with no serious adverse events, and only mild to moderate adverse events reported to date. The study is planned to continue enrollment in pediatric patients ≥ 2 years of age. The FDA’s Fast Track program is designed to facilitate the development and expedite the review of novel potential therapies intended to treat serious conditions and address significant unmet medical needs. Companies whose programs are granted Fast Track designation are eligible for more frequent interactions with the FDA during clinical development and potentially accelerated approval and/or priority review, if relevant criteria are met. About GLM101 GLM101 is a mannose-1-phosphate replacement therapy in development to treat phosphomannomutase 2-congenital disorder of glycosylation (PMM2-CDG), previously known as CDG Type Ia. GLM101 has received Orphan Drug Designation in the U.S. and Europe and Rare Pediatric Disease Designation in the U.S. PMM2-CDG is caused by genetic mutations that lead to a deficiency of the enzyme phosphomannomutase 2 (encoded by the PMM2 gene). GLM101 is designed to deliver mannose-1-phosphate directly into cells and thereby bypass the PMM2 enzyme deficiency and address disease-causing PMM2 mutations to restore pathway function. About Glycomine, Inc. Glycomine is a clinical-stage biotechnology company developing novel drugs for serious rare disorders of metabolism and protein misfolding for which no other therapeutic options exist. The company's approach is to use replacement therapies – substrates, enzymes, or proteins – and to target those molecules to clinically relevant cellular compartments. The company is based in San Carlos, California and supported by leading international life sciences investors. For more info visit www.glycomine.com .

SAN CARLOS, Calif.--( BUSINESS WIRE )-- Glycomine, Inc. , a biotechnology company focused on developing new therapies for orphan diseases, announced today that the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation for GLM101, a mannose-1-phosphate replacement therapy in development for the treatment of patients with phosphomannomutase 2-congenital disorder of glycosylation (PMM2-CDG). “Fast Track Designation for GLM101 highlights its potential to meet the serious unmet medical need of patients with PMM2-CDG,” said Rose Marino, M.D., Chief Medical Officer of Glycomine. “As we continue to enroll pediatric patients in our Phase 2 clinical study, we are encouraged by our initial data showing promising evidence of clinical benefit with GLM101. We look forward to progressing development of GLM101 within the Fast Track framework.” The GLM101-002 Phase 2 clinical study has enrolled 10 adult and five adolescent patients with PMM2-CDG in the U.S. and Spain (ClinicalTrials.gov Identifier: NCT05549219). Study participants have completed treatment with GLM101 at either 10 mg/kg (n=3), 20 mg/kg (n=3), or 30 mg/kg (n=9) for up to 24 weeks. More than 350 doses of GLM101 have been administered to PMM2-CDG patients. The drug appears to be well tolerated with no serious adverse events, and only mild to moderate adverse events reported to date. The study is planned to continue enrollment in pediatric patients ≥ 2 years of age. The FDA’s Fast Track program is designed to facilitate the development and expedite the review of novel potential therapies intended to treat serious conditions and address significant unmet medical needs. Companies whose programs are granted Fast Track designation are eligible for more frequent interactions with the FDA during clinical development and potentially accelerated approval and/or priority review, if relevant criteria are met. About GLM101 GLM101 is a mannose-1-phosphate replacement therapy in development to treat phosphomannomutase 2-congenital disorder of glycosylation (PMM2-CDG), previously known as CDG Type Ia. GLM101 has received Orphan Drug Designation in the U.S. and Europe and Rare Pediatric Disease Designation in the U.S. PMM2-CDG is caused by genetic mutations that lead to a deficiency of the enzyme phosphomannomutase 2 (encoded by the PMM2 gene). GLM101 is designed to deliver mannose-1-phosphate directly into cells and thereby bypass the PMM2 enzyme deficiency and address disease-causing PMM2 mutations to restore pathway function. About Glycomine, Inc. Glycomine is a clinical-stage biotechnology company developing novel drugs for serious rare disorders of metabolism and protein misfolding for which no other therapeutic options exist. The company's approach is to use replacement therapies – substrates, enzymes, or proteins – and to target those molecules to clinically relevant cellular compartments. The company is based in San Carlos, California and supported by leading international life sciences investors. For more info visit www.glycomine.com .