Applied Therapeutics Hits Bump After FDA Requests More Data for NDA


2022-01-04 03:30:07 BioSpace


Shares of Applied Therapeutics have plunged more than 26% in premarket trading after the company announced it is unable to seek regulatory approval of its Galactosemia therapeutic at this time. This morning, New York-based Applied Therapeutics said it is holding off on a New Drug Application. The decision came after discussions with the U.S. Food and Drug Administration (FDA). Citing the regulatory agency, it appears additional clinical data will have to be submitted.  Applied Therapeutics is developing AT-007, a central nervous system penetrant Aldose Reductase inhibitor (ARI) for the treatment of Galactosemia and other rare neurological diseases, including SORD Deficiency and PMM2-CDG. AT-007 is currently being assessed in the Phase III ACTION-Galactosemia Kids clinical trial in children ages 2-17 who have Galactosemia, a rare genetic metabolic disease that causes an inability to metabolize the simple sugar galactose.  The study assessed clinical outcomes every six months by what the company described as a firewalled committee. The first assessment is expected to be completed in the first quarter of 2022 and then every six months thereafter until the study reaches statistical significance. “While disappointed by this change in direction by the FDA, we remain committed to bringing this important treatment to patients with Galactosemia,” Shoshana Shendelman, founder, chairman and chief executive officer of Applied Therapeutics said in a statement. “We will continue to work with the FDA to determine the most expeditious path forward to regulatory approval and will provide an update on timing and plans accordingly.” In previous clinical studies, AT-007 significantly reduced plasma galactitol levels compared to placebo in adults and children with Galactosemia. There are approximately 3,000 patients with Galactosemia in the United States.  The only natural treatment for Galactosemia is to avoid foods containing milk and all dairy products. AT-007 has received both Orphan Drug and Pediatric Rare Disease designations from the FDA for the treatment of Galactosemia and PMM2-CDG. In June, AT-007 received Fast Track designation for Galactosemia. After the receipt of the Fast Track designation, Applied Therapeutics initially announced plans to submit a NDA.  When the FDA granted Fast Track designation, Shendelman noted that patients with Galactosemia typically see their issue worsen over time, which can significantly impact their quality of life. With no drugs currently approved for the rare disease, Shendelman said the company believes that AT-007 has the potential to be the first drug approved for patients.  In December, the company initiated its Phase II/III study of AT-007 in Sorbitol Dehydrogenase (SORD) Deficiency, a disease caused by the lack of the enzyme sorbitol dehydrogenase, which is responsible for the metabolism of sorbitol. The condition causes sorbitol to accumulate at high levels and become toxic to the body. SORD Deficiency affects approximately 3,300 patients in the U.S. and 4,000 patients in Europe.
应用治疗公司(Application Therapeutics)的股价在上市前交易中暴跌逾26%,此前该公司宣布,目前无法寻求监管机构对其半乳糖血症治疗方案的批准。 今天早上,总部位于纽约的应用治疗公司表示,它正在推迟一项新药应用。这一决定是在与美国食品药品监督管理局(FDA)讨论后做出的。援引监管机构的话说,似乎必须提交额外的临床数据。 应用治疗学正在开发AT-007,一种中枢神经系统渗透醛糖还原酶抑制剂(ARI),用于治疗半乳糖血症和其他罕见的神经疾病,包括SORD缺乏症和PMM2-CDG。AT-007目前正在III期行动-半乳糖血症儿童临床试验中评估,这些儿童的年龄为2-17岁,患有半乳糖血症,是一种罕见的遗传代谢病,导致无法代谢简单的糖半乳糖。 该研究每六个月评估一次临床结果,该公司称之为防火墙委员会。第一次评估预计将于2022年第一季度完成,此后每六个月完成一次,直到研究达到统计意义。 应用治疗学公司的创始人、董事长兼首席执行官肖莎娜·申德尔曼(Shoshana Shendelman)在一份声明中说:“虽然对美国食品和药物管理局的这一方向变化感到失望,但我们仍然致力于为半乳糖血症患者带来这种重要的治疗。”“我们将继续与美国食品和药物管理局合作,确定获得监管批准的最快捷途径,并将相应地提供时间和计划的最新情况。” 在以前的临床研究中,与安慰剂相比,AT-007显著降低了半乳糖血症成人和儿童的血浆半乳糖醇水平。在美国大约有3000名半乳糖血症患者。 半乳糖血症的唯一自然治疗方法是避免含有牛奶的食物和所有乳制品。 AT-007已从FDA获得治疗半乳糖血症和PMM2-CDG的孤儿药和儿科罕见病药。6月,AT-007接受了半乳糖血症的快速通道指定。在收到快速通道指定后,应用治疗学最初宣布计划提交一份NDA。 当FDA批准快速通道指定时,Shendelman指出,半乳糖血症患者通常会随着时间的推移而恶化,这可能会显著影响他们的生活质量。由于目前没有针对这种罕见疾病的药物被批准,申德尔曼说,该公司认为AT-007有可能成为第一种被批准用于患者的药物。 去年12月,该公司启动了山梨醇脱氢酶(SORD)缺乏症AT-007的II/III期研究,山梨醇脱氢酶是一种由缺乏负责山梨醇代谢的酶山梨醇脱氢酶引起的疾病。这种情况导致山梨醇在高水平上积累,并对身体有毒。SORD缺乏症在美国影响了大约3300名患者,在欧洲影响了4000名患者。