Acelyrin Discontinues Izokibep Following Unsuccessful Phase IIb/III Results in Uveitis Trials

Acelyrin Discontinues Izokibep Following Unsuccessful Phase IIb/III Results in Uveitis Trials

Acelyrin Discontinues Izokibep Following Unsuccessful Phase IIb/III Results in Uveitis Trials

On Tuesday, Acelyrin made the announcement to cease development of its IL-17A inhibitor izokibep following an unsuccessful Phase IIb/III trial targeting uveitis.

The decision to discontinue development represents yet another challenge in the journey of izokibep. Back in September 2023, the IL-17A blocker experienced setbacks in a Phase IIb/III trial for hidradenitis suppurativa, where it failed to produce a significant clinical response compared to a placebo. Subsequently, in November 2023, Acelyrin had to review its izokibep studies after uncovering critical dosing errors made by its external contract research organization.

Expressing disappointment over the trial’s inability to meet its primary goals, CEO Mina Kim stated that in line with the company’s “prioritization strategy,” no further investments would be allocated to izokibep.

The uveitis study revealed a sobering conclusion: by the 24-week mark, izokibep had not succeeded in 45% of patients, and its treatment effect failed to achieve statistical significance, as detailed in Acelyrin’s press release. Additionally, secondary endpoints, including best-corrected visual acuity and visual functioning, also did not meet statistical significance thresholds, indicating no clinical benefit from the candidate.

Following this announcement, Acelyrin’s stock plummeted by 16% in extended trading on Tuesday, based on information from Seeking Alpha.

Izokibep is characterized as a small therapeutic protein that targets and inhibits the IL-17A cytokine, integral to the inflammatory process. According to Acelyrin’s website, this candidate was crafted particularly to “overcome the drawbacks of monoclonal antibodies.” Its small size was intended to facilitate better tissue penetration and enhanced potency, allowing for high exposure with just a single subcutaneous injection, in contrast to monoclonal antibodies requiring intravenous administration to attain similar outcomes.

Moving forward, Acelyrin intends to concentrate on lonigutamab, a subcutaneous monoclonal antibody aimed at treating thyroid eye disease, as indicated by Kim in her statement. Currently in a Phase II study, lonigutamab targets the IGF-1R protein involved in the inflammatory mechanisms affecting the eyes. Acelyrin is “on course” to initiate Phase III trials for lonigutamab in the first quarter of 2025, as noted by Kim.