Zydus' Usnoflast Receives FDA Orphan Drug Designation and Phase 2b Trial Approval for ALS Treatment
Key Insights
The FDA has granted Orphan Drug Designation to Zydus' Usnoflast for treating amyotrophic lateral sclerosis (search) (ALS (search)), a rare neurodegenerative disease.
A Phase 2b clinical trial of Usnoflast in ALS (search) patients has been approved by the FDA, with Prof. Merit Cudkowicz as the principal investigator.
The Phase 2b trial will enroll 210 ALS (search) patients to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of Usnoflast over 36 weeks.
Zydus Lifesciences has achieved two significant milestones in the development of Usnoflast (ZYIL1) for amyotrophic lateral sclerosis (search) (ALS (search)). The U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to Usnoflast and has also approved the initiation of a Phase 2b clinical trial for the treatment of ALS. These developments highlight the urgent need for new therapies to combat this fatal neurodegenerative disease, which affects approximately 32,000 people in the U.S.A., with around 5,000 new cases diagnosed annually.
Orphan Drug Designation for Usnoflast
The FDA's Orphan Drug Designation provides Zydus with certain development incentives, including tax credits for qualified clinical testing, prescription drug user fee exemptions, and potential seven-year marketing exclusivity upon FDA approval. This designation underscores the FDA's recognition of the unmet need for effective treatments for rare diseases like ALS (search).
Pankaj Patel, Chairman of Zydus Lifesciences Limited, stated, "This Orphan Drug Designation from the USFDA underlines the urgent need to develop Usnoflast to address Amyotrophic Lateral Sclerosis (search) (ALS (search)), which is a fatal neurodegenerative disease. Zydus is committed to unlocking new frontiers in neuroscience and develop Usnoflast for patients with ALS."
Phase 2b Clinical Trial Approval
The FDA has also approved Zydus to proceed with a Phase 2b, randomized, double-blind, placebo-controlled, parallel-group, multicenter study to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of Usnoflast in adult subjects with ALS (search). The trial will be led by Prof. Merit Cudkowicz, MD, Director of the Sean M. Healey & AMG Center for ALS; Chair of Neurology, Massachusetts General Hospital; and Julieanne Dorn Professor of Neurology, Harvard Medical School.
The Phase 2b trial will enroll 210 ALS (search) patients who will receive either 50 mg or 75 mg of Usnoflast or a placebo for 36 weeks, followed by a 16-week open-label extension. The primary endpoint of the trial is the change in the ALS Functional Rating Scale-Revised (ALSFRS-R) total score from baseline through week 36. Key secondary endpoints include changes in Slow Vital Capacity (SVC) and CSF levels of neurofilament light chain (NfL).
Additionally, the trial will evaluate biomarkers such as high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-18, IL-6, IL-1β, NLRP3 (search), and serum amyloid A (SAA).
Usnoflast: A Novel NLRP3 Inhibitor
Usnoflast (ZYIL1) is a novel, oral small molecule NLRP3 (search) inhibitor. It has been studied in several pre-clinical models of neuroinflammation, Parkinson’s disease (search), Inflammatory Bowel Disease (search) (IBD), and Multiple Sclerosis (search) (MS). In ALS (search), Usnoflast aims to reduce inflammation by blocking the NLRP3 inflammasome, a group of proteins that can sense and respond to danger, contributing to the disease-driving inflammation.
Zydus previously completed a Phase 2a randomized, double-blind, placebo-controlled clinical trial in 24 ALS (search) patients across 7 clinical trial sites in India. The company plans to present the Phase 2a trial data at an upcoming medical conference and publish it in a medical journal.
With the Orphan Drug Designation and the approval to initiate the Phase 2b clinical trial, Zydus is poised to advance the development of Usnoflast as a potential new treatment option for ALS (search) patients, addressing a critical unmet medical need.