Applied Therapeutics Receives Complete Response Letter from U.S. FDA Regarding New Drug Application for Govorestat for Classic Galactosemia
Applied Therapeutics (APLT) received a Complete Response Letter (CRL) from the FDA regarding its New Drug Application for govorestat, a CNS-penetrant aldose reductase inhibitor for treating Classic Galactosemia. The FDA cannot approve the application citing clinical deficiencies. The company plans to request a meeting to discuss resubmission requirements or appeal the decision. Despite this setback, clinical trials showed govorestat's effectiveness in reducing galactitol levels and improving clinical outcomes in pediatric patients, including benefits in daily activities, behavior, cognition, and motor skills. The company maintains its plans to submit an NDA for govorestat in SORD Deficiency treatment in early Q1 2025.
Applied Therapeutics (APLT) ha ricevuto una Lettera di Risposta Completa (CRL) dalla FDA riguardo alla sua Richiesta di Nuovo Farmaco per govorestat, un inibitore della aldose reduttasi penetrante nel SNC per il trattamento della Galattosemia Classica. La FDA non può approvare la domanda citando carenze cliniche. L'azienda prevede di richiedere un incontro per discutere i requisiti per la ri-sottomissione o per fare appello alla decisione. Nonostante questo intoppo, gli studi clinici hanno dimostrato l'efficacia di govorestat nella riduzione dei livelli di galattitolo e nel miglioramento degli esiti clinici nei pazienti pediatrici, inclusi i benefici nelle attività quotidiane, nel comportamento, nella cognizione e nelle abilità motorie. L'azienda mantiene i suoi piani per presentare una NDA per govorestat nel trattamento della Deficienza SORD all'inizio del primo trimestre del 2025.
Applied Therapeutics (APLT) recibió una Carta de Respuesta Completa (CRL) de la FDA respecto a su Solicitud de Nuevo Medicamento para govorestat, un inhibidor de la aldosa reductasa que penetra en el SNC para tratar la Galactosemia Clásica. La FDA no puede aprobar la solicitud citando deficiencias clínicas. La empresa planea solicitar una reunión para discutir los requisitos de reenvío o apelar la decisión. A pesar de este contratiempo, los ensayos clínicos mostraron la efectividad de govorestat en la reducción de los niveles de galactitol y en la mejora de los resultados clínicos en pacientes pediátricos, incluyendo beneficios en actividades diarias, comportamiento, cognición y habilidades motoras. La empresa mantiene sus planes de presentar una NDA para govorestat en el tratamiento de la Deficiencia SORD a principios del primer trimestre de 2025.
Applied Therapeutics (APLT)는 govorestat에 대한 신규 의약품 신청 건에 대해 FDA로부터 완전 응답 서한(CRL)을 받았습니다. govorestat은 고전적인 갈락토스혈증 치료를 위한 CNS 침투형 알도오스 환원효소 억제제입니다. FDA는 임상적 결함을 이유로 신청을 승인할 수 없습니다. 회사는 재제출 요구 사항에 대해 논의하기 위해 미팅 요청을 계획 중이며, 결정을 항소할 수도 있습니다. 이러한 차질에도 불구하고 임상 시험에서는 govorestat이 갈락톨 수준을 줄이고 소아 환자에서 임상 결과를 개선하는 데 효과적임을 보여주었습니다. 여기에는 일상 활동, 행동, 인지 및 운동 능력에서의 이점이 포함됩니다. 회사는 2025년 1분기 초에 SORD 결핍 치료를 위한 govorestat에 대한 NDA를 제출할 계획을 유지하고 있습니다.
Applied Therapeutics (APLT) a reçu une Lettre de Réponse Complète (CRL) de la FDA concernant sa Demande de Nouveau Médicament pour govorestat, un inhibiteur de l'aldose réductase pénétrant dans le SNC pour le traitement de la Galactosémie Classique. La FDA ne peut pas approuver la demande en invoquant des lacunes cliniques. L'entreprise prévoit de demander une réunion pour discuter des exigences de nouvelle soumission ou pour faire appel de la décision. Malgré ce revers, les essais cliniques ont montré l'efficacité de govorestat à réduire les niveaux de galactitol et à améliorer les résultats cliniques chez les patients pédiatriques, y compris des bénéfices dans les activités quotidiennes, le comportement, la cognition et les compétences motrices. L'entreprise maintient ses projets de soumettre une NDA pour govorestat dans le traitement de la Déficience SORD début Q1 2025.
Applied Therapeutics (APLT) erhielt von der FDA einen Vollständigen Antwortbrief (CRL) zu seinem Antrag auf Zulassung eines neuen Arzneimittels für govorestat, einen CNS-durchdringenden Aldose-Reduktase-Hemmer zur Behandlung der klassischen Galaktosämie. Die FDA kann den Antrag wegen klinischer Mängel nicht genehmigen. Das Unternehmen plant, ein Treffen anzufordern, um die Anforderungen für eine Neueinreichung zu besprechen oder um die Entscheidung anzufechten. Trotz dieses Rückschlags zeigten klinische Studien die Wirksamkeit von govorestat bei der Reduzierung von Galaktitolspiegeln und der Verbesserung klinischer Ergebnisse bei pädiatrischen Patienten, einschließlich Vorteile bei täglichen Aktivitäten, Verhalten, Kognition und motorischen Fähigkeiten. Das Unternehmen hält an seinen Plänen fest, Anfang Q1 2025 einen NDA für govorestat zur Behandlung von SORD-Mangel einzureichen.
- Clinical trials demonstrated efficacy in reducing galactitol levels
- Showed benefits in pediatric patients across multiple outcomes
- Robust safety and efficacy data from 185 patients over 3 years
- Alternative development pathway for SORD Deficiency remains active
- FDA rejected the New Drug Application for govorestat
- Clinical application deficiencies cited by FDA
- Delay in potential market entry for Classic Galactosemia treatment
- Additional regulatory requirements may increase development costs
Insights
The FDA's Complete Response Letter (CRL) for govorestat represents a significant setback for Applied Therapeutics. Despite promising clinical data showing improvements in cognitive function, behavior and motor skills in Galactosemia patients, the FDA found deficiencies in the clinical application that prevent approval. The impact is particularly notable given that:
- There are currently no approved treatments for Classic Galactosemia
- The company has invested significantly in clinical trials, with data from 185 patients over 3 years
- The drug demonstrated efficacy in reducing galactitol levels and improving daily living activities
However, the company's parallel development of govorestat for SORD Deficiency, with an NDA submission planned for Q1 2025, provides a potential alternative pathway for value creation. The stock impact may be partially mitigated by this separate opportunity and the company's commitment to address the FDA's concerns.
This CRL significantly impacts APLT's near-term commercialization prospects and cash runway. The delay in potential approval will require additional resources for addressing FDA concerns and possibly conducting new studies. Key financial considerations include:
- Increased cash burn from potential additional clinical work
- Delayed revenue timeline from Galactosemia indication
- Potential need for additional capital raising
The separate SORD Deficiency program becomes important as a value driver, but investors should monitor cash position closely. The market cap of
NEW YORK, Nov. 27, 2024 (GLOBE NEWSWIRE) -- 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.
About Govorestat (AT-007)
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.
About 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.
About Applied Therapeutics
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).
To learn more, please visit www.appliedtherapeutics.com.
Forward-Looking Statements
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FAQ
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