Acelyrin sent a chill rippling through the IPO market in September when its phase 3 clinical trial unexpectedly failed. But now the company says some errors by the contract research organization running the study may have been to blame.
The biotech reported that its lead prospect izokibep failed the late-stage portion of a phase 2b/3 study in patients with moderate to severe hidradenitis suppurativa in September. The IL-17A inhibitor, which had set out to challenge industry heavyweights like Eli Lilly’s Taltz and Novartis’ Cosentyx, did not beat placebo on the primary endpoint of achieving a 75% or greater improvement in total abscess and inflammatory nodule count.
The results, which arrived just months after Acelyrin’s massive $540 million IPO, sent a shockwave across the sector. Acelyrin has an expansive program with multiple indications underway, so the failure of one clinical trial was potentially troublesome.
In a post-market release Monday, Acelyrin provided an update on the izokibep program explaining that a programming error had been identified in one study. Patients in two groups of a study for psoriatic arthritis (PsA) were not dosed as planned. Now, the company is taking a broader look at the entire izokibep program, including the apparent failure in hidradenitis suppurativa. The CRO involved is Fortrea, according to a related SEC filing (PDF).
The PsA trial had four arms: 160 mg weekly; 160 mg every other week; 80 mg every four weeks; and the placebo group. Acelyrin apparently provided the correct protocol with the outlined dosing sequences. However, the biotech claimed that information was programmed incorrectly by a vendor working with Fortrea. This error was not identified by the CRO’s testing processes, according to Acelyrin.
It meant that some patients in the group receiving a 160 mg dose every other week as well as some of those in the 80 mg cohort received placebo and active treatment in random order rather than alternating as intended.
Acelyrin said there was no risk to patients due to the error and no one received more active ingredients than the protocol had allowed for.
The error has now been addressed and the dosing sequence fixed. Acelyrin has no reason to believe the other arms of the trial were in any way affected. But the company is still figuring out the implications of the sequencing errors on the trial groups that did receive the wrong dosing.
Acelyrin is continuing to review all of Fortrea’s work and plans to consult a third party for an independent audit. The review includes the apparent failure of the hidradenitis suppurativa trial. Top-line data from a phase 2b/3 trial in PsA are due in the first quarter of 2024, which Acelyrin said is still on track pending completion of the third-party’s evaluation.
Meanwhile, Acelyrin pledged to never use Fortrea for any new trials it plans to conduct.
“Based on the outcome of its ongoing evaluation and the planned audit, the company will determine the best path forward for the development of izokibep on behalf of patients. This will include a determination of whether to transition its ongoing trials to a new CRO or complete the trials with the current CRO,” the update stated.
Fortrea disagreed with certain aspects of Acelyrin's description of the situation in a statement provided to Fierce Biotech, but declined to speculate on what may have happened until the audit is complete.
"A Fortrea customer made concerning statements about errors in clinical trials that Fortrea managed on its behalf. We are taking swift and decisive action to investigate this matter along with a comprehensive audit with the third-party vendor," the statement said. "We have successfully conducted clinical trials for more than 30 years, all while upholding the highest standards of integrity for our valued customers. We have an unwavering commitment to the safety and well-being of patients and clinical trial participants, to data integrity, and to the ethical conduct of clinical trials."
Fortrea is a new name in biotech but spun out of Labcorp in February, taking the lab diagnostic giant's drug and medical device development services into a new publicly-traded company.
The CRO said that there is no reason to believe there are any issue with the results of the hidradenitis suppurativa trial and the error was made by a third party and not Fortrea.
"Fortrea disagrees with certain aspects of its customer's description of the situation and clarifies key points in the statement," Fortrea's statement said. "We are unaware of any basis for the customer to suggest errors in the conduct of its previous study evaluating the investigational product for the treatment of moderate-to-severe hidradenitis suppurativa and we have no reason to question the results of that study."
The statement continued: "In accordance with our shared responsibility of study oversight under applicable regulations, we are working with the customer to further understand the details and impact."
Fortrea was listed in the SEC filing as notifying European regulators about the error along with Acelyrin on Nov. 26.
Acelyrin recently presented data in the psoriatic arthritis indication from a phase 2 trial that was not conducted by Fortrea. These results showed dose-ordered responses as early as one month into treatment that increased over time. Longer-term follow-up showed durable and deepening resolution of disease.
“We are disappointed by these developments, especially for the patients who need better treatment options for psoriatic arthritis and hidradenitis suppurativa,” said Acelyrin CEO Shao-Lee Lin, M.D., Ph.D.
“However, we are a company founded on truth and transparency, and we are grateful that through the tenacity of our internal team we were able to identify these errors,” Shao-Lee added. “We are committed to delivering the best possible outcome for patients, physicians and shareholders as we continue to pursue development of izokibep as a potentially differentiated treatment for multiple immunologic conditions.”
Due to the recent developments, Acelyrin canceled two scheduled investor conference appearances.
Editor's Note: This story was updated at 10:37 a.m. ET on November 28, 2023, to clarify that the error was identified in the PsA trial, not the completed hidradenitis suppurativa study. Results of that trial are under review. A statement from Fortrea was also added.