FDA favors Phase 2 trial of oral ZYIL1 in Parkinson’s patients

Potential therapy aims to counter brain inflammation, protect nerve cells

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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The U.S. Food and Drug Administration (FDA) has given Zydus Lifesciences a green light to conduct a Phase 2 trial of ZYIL1, an oral inhibitor of NLRP3 — a protein that’s linked to brain inflammation, or neuroinflammation — in people with Parkinson’s disease.

The trial will evaluate the safety and tolerability of ZYIL1, as well as its pharmacokinetics and pharmacodynamics, in patients. Pharmacokinetics refers to the movement of a medicine into, through, and out of the body, while pharmacodynamics looks at a  compound’s effects on the body.

“Our team is developing a novel, disease modifying approach through inhibiting the activation of NLRP3 inflammasome with ZYIL1, which could potentially reduce neuroinflammation and neuro-degeneration in patients suffering from Parkinson’s disease,” Pankaj R. Patel, chairman of Zydus, said in a company press release.

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The NLRP3 protein works as a sensor inside cells for a broad range of danger signals, including pathogens and other harmful agents. Once a threat is detected, it triggers the formation of an inflammasome, a molecular complex involved in inflammatory responses.

While this is paramount for the immune system to defend against threats, overactivation of the NLRP3 protein can lead to brain inflammation in people with diseases like Parkinson’s, Alzheimer’s, and amyotrophic lateral sclerosis (ALS).

Zydus reports that its investigational therapy was seen to enter the brain and cerebrospinal fluid (the fluid surrounding the brain and spinal cord) in preclinical studies in mice, rats, and nonhuman primates.

Its efficacy in targeting the NLRP3 protein and suppressing inflammation also has been validated in preclinical models of neuroinflammation and Parkinson’s disease, the company noted, with reasonable safety shown.

Two Phase 1 trials conducted in India tested the safety and tolerability of ZYIL1 administered as single (NCT04731324) and multiple (NCT04972188) doses in a total of 48 healthy adults.

Results from these studies showed that ZYIL1 was well tolerated up to a single dose of 400 mg and in multiple doses of up to 100 mg taken twice daily for 14 days.

The candidate therapy currently is being evaluated in a Phase 2 trial (NCT05981040) in people with ALS. The trial, underway at a single site in India, is currently recruiting eligible adult patients.

ZYIL1 also showed good safety and tolerability in a small proof-of-concept Phase 2 study (NCT05186051) in patients with a rare hereditary inflammatory condition called cryopyrin-associated periodic syndrome, treated with 50 mg capsules twice daily for seven days.

The potential treatment has been given orphan drug status in the U.S. for this syndrome, a designation aiming to encourage therapy development for rare and serious diseases through benefits such as seven years of market exclusivity and an exemption from FDA application fees.