Zydus’ usnoflast wins FDA’s fast track drug status for treating ALS
Therapy was named orphan drug earlier this year
The U.S. Food and Drug Administration (FDA) has granted fast track status to usnoflast, Zydus Lifesciences’ experimental oral inhibitor, for treating amyotrophic lateral sclerosis (ALS).
The designation is meant to accelerate the development and review of new therapies that address unmet medical needs in serious or life-threatening conditions, and makes Zydus eligible for more frequent meetings and discussions with the FDA throughout the drug development process. A fast track designation also makes a drug eligible for accelerated approval and priority review, if certain criteria are met, the goal being to make important new drugs available sooner.
The FDA also granted usnoflast orphan drug status for ALS earlier this year. This designation is intended to accelerate the development of treatments for rare conditions by offering a range of incentives, including fee exemptions and a seven-year period of market exclusivity, if approved.
“This ‘fast track designation,’ in addition to the previous ‘orphan drug designation’ granted by the [FDA], underlines the urgent need to develop treatments to address amyotrophic lateral sclerosis (ALS),” Pankaj Patel, chairman at Zydus, said in a company press release. “Zydus is committed to unlocking new frontiers in neuroscience and develop usnoflast for patients with ALS.”
Studying usnoflast in ALS
Previously called ZYIL1, usnoflast is an orally available small molecule that’s designed to reduce inflammation, a key contributor to nerve cell damage and death in ALS, by blocking the activity of the NLRP3 inflammasome. NLRP3 is a group of proteins that can detect danger signals and initiate immune responses to help the body eliminate the invaders. It’s overactive in ALS, making it a promising target for treatment.
After being deemed well tolerated at single and multiple doses in healthy volunteers, with promising signs that it was inhibiting the NLRP3 inflammasome as intended, usnoflast was tested in a Phase 2a trial (NCT05981040) in India.
The study enrolled 24 ALS patients whose symptoms had started up to nine months before they’d joined. The participants received one of three doses of usnoflast (25, 50, and 75 mg) or a placebo, twice daily for three months.
The main goal was to determine if the treatment could slow ALS progression, as measured by changes in ALS Functional Rating Scale-Revised (ALSFRS-R) scores. Secondary measures included changes in lung function, time to death or permanent breathing support, and treatment safety. Some pharmacological properties of the treatment were also assessed.
The trial is complete, but its results haven’t yet been shared by the company, which said in January it would present the data at an upcoming medical conference and publish it in a medical journal.
Meanwhile, Zydus has been cleared to initiate a Phase 2b trial in the U.S. This study is expected to enroll about 210 adults with ALS, who will receive one of two doses (50 or 75 mg), or a placebo, for about eight months. The patients may then enter an open-label extension, where they’ll receive usnoflast for another four months. The main goal is also to see if usnoflast can slow ALSFRS-R decline. Secondary goals include changes in lung function and several ALS biomarkers.
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