The discontinuation caps off a turbulent development path for izokibep, which in September 2023 produced disappointing results from Phase IIb/III study in hidradenitis suppurativa that was found to have had dosing errors.
Acelyrin on Tuesday announced that it will discontinue the development of its investigational IL-17A blocker izokibep following a failed Phase IIb/III trial in uveitis.
The discontinuation of its development on Tuesday ends what has been a rough road for izokibep. In September 2023, the IL-17A inhibitor failed a Phase IIb/III study in hidradenitis suppurativa, unable to elicit a significantly better clinical response than placebo. A few months later, in November 2023, Acelyrin was forced to conduct a review of its izokiep studies after it discovered key dosing errors conducted by a third-party contract research organization.
CEO Mina Kim in a statement said that the company is “disappointed” that the trial fell short of its primary endpoint, but in keeping with its “previously announced prioritization strategy,” it will no longer invest additional resources into izokibep.
The final blow came in the uveitis study, which found that at 24 weeks, izokibep treatment had failed in 45% of patients, with its treatment effect failing to reach statistical significance, according to Acelyrin’s news release. The secondary endpoints—including best-corrected visual acuity and visual function—also fell short of statistical significance, and the drug candidate did not show clinical benefit.
Acelyrin was down 16% in extended trading on Tuesday following the announcement, according to Seeking Alpha.
Izokibep is a small protein therapeutic candidate that works by targeting and blocking the IL-17A cytokine, a key player in the inflammatory pathway. With its small molecular size, izokibep was designed specifically to “overcome the limitations of monoclonal antibodies,” according to Acelyrin’s website. Aside from its size, the molecule was built to have enhanced tissue penetration and potency, enabling it to reach high exposure levels with a single subcutaneous injection—whereas monoclonal antibody therapies need to be intravenously delivered to achieve a similar effect, Acelyrin posits.
Acelyrin will now focus its efforts on lonigutamab, a subcutaneous monoclonal antibody being developed for thyroid eye disease, Kim said in the company’s statement.
Lonigutamab targets the IGF-1R protein, which is involved in the pathological inflammatory process that can affect the eyes. The candidate is currently in a Phase II study. Acelyrin is “on track” to launch its Phase III development program of lonigutamab in the first quarter of 2025, Kim said.
