Zydus Lifesciences completes Phase II(a) clinical trial of Usnoflast in ALS patients

New Delhi: Zydus Lifescience has announced the completion of its Phase II(a) clinical trial of Usnoflast, a novel oral NLRP3 inflammasome inhibitor, in patients with Amyotrophic Lateral Sclerosis (ALS). This marks a development in treatments for ALS, a neurodegenerative disorder characterized by rapid deterioration of motor neurons, leading to paralysis and ultimately death.

ALS affects over 32,000 individuals in the United States, with approximately 5,000 new cases diagnosed each year. In Europe, around 30,000 people live with the disease, while India has an estimated 75,000 ALS patients. Most individuals diagnosed with ALS face an average survival time of two to five years, with respiratory failure being the primary cause of death.

Zydus’s Usnoflast, also known as ZYIL1, is the first NLRP3 inhibitor to demonstrate proof-of-concept in ALS patients. The 12-week randomized, double-blind, placebo-controlled trial recruited 24 ALS patients across seven clinical sites in India. The study evaluated the drug’s safety, tolerability, pharmacokinetics, and pharmacodynamics. Usnoflast was well tolerated, with therapeutic concentrations achieved in both the plasma and cerebrospinal fluid (CSF) of ALS patients.

The trial showed promising results, with a favorable trend towards reducing levels of Neurofilament Light chain (NfL), a biomarker of neurodegeneration. Reductions in NfL levels suggest a slowing of disease progression, providing hope for future treatment options. In addition, improvements were noted in the ALS Functional Rating Scale (ALSFRS-R) and Slow Vital Capacity (SVC), both of which are key indicators of ALS patient health and disease progression.

Commenting on the development, Pankaj Patel, Chairman of 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 the ALSFRS-R score. The improvement observed in SVC 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.”

Usnoflast’s mechanism of action involves inhibiting the NLRP3 inflammasome, a protein complex that plays a critical role in inflammation and neurodegenerative diseases. By suppressing this inflammasome, Usnoflast may help reduce the inflammation that accelerates neurodegeneration in ALS patients. Preclinical models have demonstrated its efficacy in several other diseases, including Parkinson’s disease, Inflammatory Bowel Disease (IBD), and Multiple Sclerosis (MS).

The drug has already shown promising results in earlier studies. In Phase I trials, Usnoflast was found to be safe and well-tolerated, with a good safety profile in animal models. The drug also received an Orphan Drug Designation from the US FDA for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), a rare autoinflammatory disease. Additionally, Zydus is currently conducting a Phase II clinical trial of Usnoflast in patients with Ulcerative Colitis.

Zydus plans to publish detailed clinical trial results in leading medical journals and present them at upcoming scientific conferences. As the company moves forward, it is looking ahead to larger Phase IIb trials in ALS patients to further investigate Usnoflast’s potential to combat this devastating disease.