Global pharmaceutical company Zydus has received approval from USFDA to conduct Phase II(b) clinical trial for Usnoflast, a novel oral NLRP3 inflammasome inhibitor in patients with Amyotrophic Lateral Sclerosis (ALS).

Under the leadership of Principal Investigator Prof Merit Cudkowicz, Director of the Sean M. Healey & AMG Centre for ALS; Chair of Neurology, Massachusetts General Hospital; Julieanne Dorn Professor of Neurology, Harvard Medical School, the Phase 2(b), randomised, double-blind, placebo-controlled, parallel-group, multicentre study will evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of Usnoflast administered to adult subjects with ALS.

This study consists of 36- week treatment phase, followed by a 16-week open label extension. This study will enrol 210 ALS patients and study doses of 50 mg and 75 mg Usnoflast versus placebo. The change in ALSFRS-R total score from baseline through week 36 will be measured as the primary endpoint of this trial.

The key secondary endpoints will include change in SVC (Slow Vital Capacity), CSF levels of NfL (neurofilament). In addition, the biomarkers including high sensitivity C-reactive protein, (hs-CRP), interleukin (IL)-18, IL6, IL-1β, NLRP3 and serum amyloid A (SAA), will also be evaluated.

Speaking on the development, Chairman of Zydus Lifesciences Ltd., Pankaj Patel, said, “We are excited to report the approval from USFDA to initiate this randomised, double blind, placebo- controlled Phase 2(b) clinical trial in ALS patients. Zydus is committed to unlocking new frontiers in neuroscience and develop transformative breakthrough medicines.”

People living with ALS have an average survival of approximately two to five years from diagnosis, with most ALS patients dying from respiratory failure. ALS patients experience neuroinflammation and rapid neurodegeneration. Axonal neurodegeneration leads to formation of neurofilaments which first accumulate in CSF of ALS patients, and then slowly these neurofilaments enter blood circulation.

Owing to rapid neurodegeneration, steady loss of the ability to move, speak, eat, eventually breathe, paralysis and death have been reported in ALS patients. ALS affects approximately 32,000 people in the USA and on an average 5,000 new patients are diagnosed every year with this disease in USA as per statistics from Centre for Disease Control and Prevention (CDC). More than 30,000 people are estimated to be living with ALS in Europe (European Union and United Kingdom), while India has an estimated 75,000 people living with ALS.

Usnoflast (ZYIL1) is a novel, oral small molecule NLRP3 inhibitor. Usnoflast has been studied in several pre-clinical models of neuroinflammation, Parkinson’s disease, Inflammatory Bowel Disease (IBD) and Multiple Sclerosis (MS).

The USFDA has granted Zydus an ‘Orphan Drug Designation’ for Usnoflast to treat patients with Cryopyrin Associated Periodic Syndrome (CAPS), a rare auto-inflammatory disease. Zydus has previously completed a Phase 2(a) randomised, double-blind, placebo-controlled clinical trial in 24 ALS patients across 7 clinical trial sites in India. It is planned to present this Phase 2(a) trial data in upcoming medical conference and publish in medical journal.