Zydus launches Phase 2 trial of anti-inflammatory ZYIL1

The experimental therapy for ALS suppresses effects of the NLRP3 inflammasome

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Zydus Lifesciences has launched a Phase 2 clinical trial to evaluate the safety and effectiveness of its experimental anti-inflammatory therapy ZYIL1 in people with amyotrophic lateral sclerosis (ALS).

The company announced it has received clearance for the clinical trial (NCT05981040) from India’s Central Drugs Standard Control Organization (CDSCO). The study is not recruiting patients yet, and the site(s) where it will be conducted have not been announced.

“Zydus has always aimed at improving the quality of life of patients through its life changing discoveries,” Pankaj R. Patel, chairman of Zydus, said in a press release. “This study is a positive step in this direction to address very high unmet medical needs of patients suffering with ALS.”

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ALS is characterized by the progressive death and dysfunction of motor neurons, the specialized nerve cells that control voluntary movements. Although the exact biological mechanisms that drive motor neuron dysfunction in ALS aren’t completely understood, it’s thought that inflammation plays a central role.

Under normal circumstances, the body produces an inflammatory response to fend off infections, but in neurological diseases like ALS it’s thought that out-of-control inflammation drives nerve damage.

ZYIL1 is an oral medication designed to reduce inflammation by blocking the activity of the NLRP3 inflammasome, a complex of inflammation-driving proteins that normally helps the body fight off viruses.

Preclinical studies have indicated the therapy is able to get into the brain and spinal cord of several animal models and to show beneficial effects in validated models of neuroinflammation and neurodegeneration, according to Zydus.

“By targeting neuroinflammation and neurodegeneration with ZYIL1, we hope to open up new possibilities in treating ALS,” Patel said.

Previous trials of anti-inflammatory therapy candidate ZYIL1

Two previous Phase 1 trials conducted in India tested single (NCT04731324) and multiple (NCT04972188) doses of ZYIL1 in a total of 48 healthy volunteers. Data showed the therapy was safe and well tolerated up to a single 400‐mg dose and a 100-mg dose twice daily for 14 days.

ZYIL1 also was found to have a favorable pharmacological profile and to effectively suppress the NLRP3 inflammasome pathway.

The newly launched Phase 2 trial will evaluate the therapy’s safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy in up to 24 adults, ages 18 to 80, who experienced the first ALS symptoms within nine months before enrollment.

Pharmacokinetics refers to the therapy’s movement into, through, and out of the body. while pharmacodynamics concerns the therapy’s effects on the body.

Participants will be assigned randomly to take receive either one of three doses of ZYIL1 (25, 50, or 75 mg) or a placebo, twice daily for 12 weeks (about three months).

Main and secondary goals of the Phase 2 trial

The study’s main goal is to assess the impact of ZYIL1 treatment on scores of the Amyotrophic Lateral Sclerosis Functional Rating Scale, a standardized measure of how much motor function is affected by ALS.

Key secondary goals include changes in a measure of lung function called slow vital capacity, as well as on blood levels of a nerve damage marker called neurofilament light chain.

ZYIL1 also is being evaluated as a potential treatment for a rare hereditary inflammatory condition called cryopyrin associated periodic syndrome and for which it received orphan drug status in the U.S. Such designation is meant to speed the therapy’s clinical development and regulatory review.