Congenital Disorders of Glycosylation

Nov. 27, 2024 -- Applied Therapeutics, Inc. (Nasdaq: APLT), a biopharmaceutical company dedicated to creating transformative treatments for rare disease, today announced that the U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) for the New Drug Application (NDA) for govorestat, a novel, central nervous system (CNS)-penetrant aldose reductase inhibitor (ARI), for the treatment of Classic Galactosemia. The CRL indicates that the FDA completed its review of the application and determined that it is unable to approve the NDA in its current form, citing deficiencies in the clinical application. Applied Therapeutics is reviewing the feedback from the FDA and plans to immediately request a meeting to discuss requirements for a potential resubmission of the NDA or appeal of the decision along with appropriate next steps. “We are disappointed by the FDA’s decision today. Our strong commitment to the Galactosemia community is rooted in our belief that govorestat has the potential to change the lives of patients with Galactosemia, which we believe is evidenced by the breadth of efficacy and safety data demonstrating its ability to stop the decline on progressive clinical outcomes, including cognition and behavior,” said Shoshana Shendelman, PhD, Founder and CEO of Applied Therapeutics. “Galactosemia is a progressive and debilitating disease without any existing treatment options and there remains a high unmet medical need for this community. As we move forward, we plan to work with the FDA to address the concerns in the CRL and determine an expeditious path to bring this much needed treatment to patients. We are grateful to the patients, families, and healthcare providers who participated in the govorestat clinical studies.” Govorestat has demonstrated rapid and sustained reductions in galactitol in clinical trials, which resulted in a meaningful benefit on clinical outcomes across pediatric patients, alongside a favorable safety profile. In the Phase 3 registrational ACTION-Galactosemia Kids study in children with Galactosemia aged 2-17, treatment with govorestat demonstrated clinical benefit on activities of daily living, behavioral symptoms, cognition, fine motor skills and tremor. Govorestat also significantly reduced plasma galactitol levels in both adults and children with Galactosemia. Additional supportive studies resulted in robust efficacy and safety data across 185 patients with Classic Galactosemia over 3 years. The results of the ACTION-Galactosemia Kids study and the Phase 1/2 ACTION-Galactosemia study in adult patients with Galactosemia were published in the Journal of Clinical Pharmacology. Govorestat is also being developed for the treatment of Sorbitol Dehydrogenase (SORD) Deficiency, a rare and progressive neuromuscular disease. The Company expects to submit an NDA early in the first quarter of 2025. The review and potential approval of govorestat for the treatment of SORD is independent of the ongoing review of govorestat for Classic Galactosemia. Govorestat is a central nervous system (CNS) penetrant Aldose Reductase Inhibitor (ARI) being developed for the treatment of multiple rare diseases including Classic Galactosemia, Sorbitol Dehydrogenase (SORD) Deficiency, and PMM2- congenital disorder of glycosylation (CDG). Govorestat has received Orphan Medicinal Product Designation from the European Medicines Agency (EMA) for both Galactosemia and SORD Deficiency. Govorestat has also received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for the treatment of Galactosemia, PMM2-CDG, and SORD Deficiency; Pediatric Rare Disease designation for Galactosemia and PMM2-CDG; and Fast Track designation for Galactosemia. Galactosemia is a rare genetic metabolic disease resulting in an inability to metabolize the simple sugar galactose. Galactose is found in foods, but is also produced endogenously by the body. When not metabolized properly, galactose is converted to the toxic metabolite, galactitol, which causes neurological complications, including deficiencies in cognition, behavior, activities of daily living, adaptive skills, fine and gross motor skills and speech, as well as tremor and seizures. There are approximately 3,300 patients with Galactosemia in the U.S. and 80-100 new births per year, and approximately 4,400 patients with Galactosemia in the E.U. and approximately 120 new births per year. Newborn screening for Galactosemia is mandatory in the U.S. and most E.U. countries. Applied Therapeutics is a clinical-stage biopharmaceutical company committed to the development of novel drug candidates against validated molecular targets in rare diseases. The Company’s lead drug candidate, govorestat, is a novel central nervous system penetrant Aldose Reductase Inhibitor (ARI) for the treatment of CNS rare metabolic diseases, including Classic Galactosemia, Sorbitol Dehydrogenase (SORD) Deficiency and PMM2-congenital disorder glycosylation (CDG). The content above comes from the network. if any infringement, please contact us to modify.

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 .