Zydus Lifesciences has announced the successful completion of a Phase IIa clinical trial for its novel NLRP3 inflammasome inhibitor, Usnoflast (ZYIL1), in patients with Amyotrophic Lateral Sclerosis (ALS). The 12-week trial, conducted across seven clinical trial sites in India, evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of Usnoflast in 24 ALS patients.
The results indicate that Usnoflast is safe and well-tolerated, achieving the desired therapeutic concentrations in both blood and cerebrospinal fluid (CSF). Notably, the trial also demonstrated a favorable trend towards the reduction of neurofilament light chain (NfL) levels in the CSF of ALS patients. NfL is a well-established biomarker of neurodegeneration, and its reduction suggests a potential neuroprotective effect of Usnoflast.
Clinical Improvements
In addition to the biomarker findings, clinicians reported improvements in the ALS Functional Rating Scale-Revised (ALSFRS-R) scores. Furthermore, encouraging improvements were observed in Slow Vital Capacity (SVC), a measure of respiratory function, in ALS patients during the 12-week trial. These clinical improvements suggest that Usnoflast may help slow the progression of ALS, a debilitating disease characterized by the gradual loss of muscle control.
Pankaj Patel, Chairman of Zydus Lifesciences Ltd, stated, "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."
About Usnoflast
Usnoflast (ZYIL1) is a novel, oral small-molecule NLRP3 inhibitor. Preclinical studies have demonstrated that Usnoflast is highly potent in human whole blood assays and can effectively suppress inflammation caused by the NLRP3 inflammasome. The drug has also shown promising distribution in the brain and CSF in various nonclinical species, including mice, rats, and non-human primates.
The efficacy of Usnoflast has been established in several preclinical models of neuroinflammation, Parkinson’s disease, Inflammatory Bowel Disease (IBD), and Multiple Sclerosis (MS). The drug also exhibits an acceptable Absorption, Distribution, Metabolism, and Excretion (ADME) profile, with a good safety margin. Previous Phase I studies have confirmed that Usnoflast is safe and well-tolerated.
ALS Disease Burden
ALS affects approximately 32,000 people in the United States, with about 5,000 new cases diagnosed each year. In Europe (European Union and United Kingdom), more than 30,000 people are estimated to be living with ALS, while India has an estimated 75,000 ALS patients. The average survival time for individuals with ALS is approximately two to five years from diagnosis, with most patients succumbing to respiratory failure.
Zydus plans to publish the detailed clinical trial results in leading medical journals and present them at upcoming scientific conferences. The company is also planning a larger Phase 2b clinical trial in consultation with regulatory authorities to further evaluate the efficacy and safety of Usnoflast in ALS patients.
