Ahmedabad: Zydus, a discovery-based, global pharmaceutical company, announced the
completion of its Phase II(a) clinical study of NLRP3 inhibitor ‘Usnoflast (ZYIL1)’ in
patients with Amyotrophic Lateral Sclerosis (ALS).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 U.S.A and on an average 5,000 new patients
are diagnosed every year with this disease in USA as per statistics from Centers 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. People living with ALS have an average survival of approximately
two to five years from diagnosis, with most ALS patients dying from respiratory failure.Speaking on the development, Mr. Pankaj Patel, Chairman, Zydus Lifesciences Limited said, “This is a first-in-class innovation and represents a significant scientific breakthrough in our
quest for finding new medicines for treating ALS patients. We are excited to report that
Usnoflast has been able to reach therapeutic concentrations in CSF of ALS patients and
reduce the neurofilaments in CSF in this initial Phase 2(a) study. Clinicians have reported
improvements in ALSFRS-R score. The improvement observed in SVC (Slow Vital
Capacity) in ALS patients has been encouraging in this 12-week trial. We now look forward
to conducting a larger Phase 2b clinical trial in consultation with the regulatory authorities.” The Phase 2(a) randomized, double-blind, placebo controlled clinical trial recruited 24 ALS
patients across 7 clinical trial sites in India and evaluated the Safety, Tolerability,
Pharmacokinetics and Pharmacodynamics of Usnoflast in Subjects with ALS
[ClinicalTrials.gov Identifier: NCT05981040]. Zydus will publish the detailed clinical trial
results in leading medical journals and upcoming scientific conferences.
Usnoflast (ZYIL1) is a novel, oral small molecule NLRP3 inhibitor. Studies have
demonstrated that Usnoflast is highly potent in human whole blood assay and can suppress
inflammation caused by the NLRP3 inflammasome. Usnoflast was found distributed in the
brain and CSF of various nonclinical species including mice, rats and non-human primates.
The efficacy of Usnoflast has been established in several pre-clinical models of
neuroinflammation, Parkinson’s disease , Inflammatory Bowel Disease (IBD) and Multiple
Sclerosis (MS). Usnoflast, has an acceptable Absorption, Distribution, Metabolism,
Excretion (ADME) profile, with a good safety margin. In Phase I studies, Usnoflast was
found to be safe and well-tolerated [NCT04731324, NCT04972188]. Zydus has established
the Phase 2 proof-of-concept in CAPS patients [NCT05186051] and had earlier published
the data in journal ‘Clinical Pharmacology in Drug Development’. 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
initiated a Phase 2 clinical study of Usnoflast in Ulcerative Colitis [ClinicalTrials.gov ID
NCT06398808].Read Also: Zydus Lifesciences bags USFDA nod for Scopolamine Transdermal System 1 mg/3 days