Acelyrin claims errors by CRO Fortrea led to late-stage trial downfall

Immunology biotech Acelyrin has determined that its CRO partner Fortrea is responsible for the late-stage failure of its immunotherapeutic drug candidate for moderate to severe hidradenitis suppurativa (HS). The company says a programming blunder by a vendor recruited by the CRO resulted in two erroneously treated patient arms going undetected through the testing processes.

Los Angeles-based Acelyrin was aiming to make waves in a fiercely competitive psoriasis market with a breakout $540m IPO in May and a steady stream of clinical data and patient enrolment updates on its izokibep clinical program. But in September, when the Phase IIb/III study (NCT05355805) failed to meet its endpoint of achieving a 75% reduction in total abscesses and inflammatory nodules, the company’s stock more than halved overnight and has not yet recovered to the levels seen before 11 September.

While a press release issued by Acelyrin outlining the error did not identify Fortrea as the CRO in question, a 26 November SEC filing stated that both Acelyrin and Fortrea notified EU regulators about the errors in the trial.

The Phase IIb/III study was a double-blind, placebo-controlled, multi-centre study evaluating the safety and efficacy of izokibep. The drug, an anti-IL-17A antibody mimetic, is designed to inhibit IL-17 signaling and block the inflammatory cascade that induces inflammation, in treating moderate to severe HS.

The study enrolled 175 patients that were divided across four treatment arms. Patients in the QW group were given once-weekly 160 mg of izokibep, and those in Q2W were given the same dose but every two weeks. Patients in Q3W received a weekly placebo until week 16 and were then given izokibep until week 31. Those in group Q4W were to be administered placebo every other week until week 14, and then izokibep until week 30.

Acelyrin states that this protocol was incorrectly used by the vendor engaged by the CRO, which resulted in some patients in two of the arms—160mg Q2W and 80 mg Q4W— receiving the investigational drug and placebo in a “random order”.  The company estimates that the other two trials arms are unlikely to be impacted by this error.

The North Carolina-based CRO is also conducting trials for Acelyrin’s Phase IIb/III study (NCT05623345) evaluating izokibep for the treatment of psoriatic arthritis (PsA). Since being made aware of the error, the company says it has corrected the programming and dosing sequence for the ongoing PsA trial and is also actively working to “determine the implications” of the errors.

Acelyrin also stated that the “confounding factors,”—namely discontinuation without adverse events and notable increases in placebo rates at the tail-end of the study—observed in the trial led to the company fortifying quality control measures for both the HS and PsA studies. Moving forward, Acelyrin plans to bring in a third-party to audit the trial work carried out by Fortrea.

Sign up for our daily news round-up!

Give your business an edge with our leading industry insights.