Acelyrin: Errors in Phase 2b/3 study

 ACELYRIN, INC. (Nasdaq: SLRN), a late-stage clinical biopharma company focused on accelerating the development and delivery of transformative medicines in immunology, today provided an update on its izokibep clinical development program, including its ongoing global Phase 2b/3 trial for izokibep in psoriatic arthritis (“PsA trial”).

Background

In September 2023, ACELYRIN disclosed top-line results from Part B of its Phase 2b/3 trial evaluating izokibep for the treatment of moderate-to-severe Hidradenitis Suppurativa (“HS trial”). Given certain confounding factors observed in the trial, including responder discontinuations without adverse events and a marked increase in placebo rates arising in the latter half of the study, the Company implemented quality control measures above and beyond standard protocol for the ongoing open-label extension of the HS trial, the ongoing Phase 3 trial in HS, and the ongoing PsA trial. These trials are being conducted by the same Contract Research Organization (CRO). The CRO does not conduct any trials on behalf of ACELYRIN beyond the izokibep clinical program.

PsA Trial

The ongoing PsA trial is designed with four arms: 160mg dosed every week (QW), 160mg dosed every other week (Q2W), 80mg dosed every four weeks (Q4W) and placebo. ACELYRIN’s team recently identified clinical trial execution errors involving its CRO and one of the vendors engaged by the CRO. ACELYRIN has confirmed that the protocol, which outlined dosing sequence, was correct. However, ACELYRIN’s protocol was programmed incorrectly by the vendor, resulting in a sequencing error that went further unidentified through the providers’ testing processes. As a result, some patients in the 160mg Q2W and 80mg Q4W arms received placebo and active treatment in random order rather than in an alternating pattern as intended. Importantly, there is no risk to patient safety resulting from the sequencing errors and no patient received more active treatment than was already included in the protocol for the most frequent 160mg QW dosing arm. The programming error has been addressed and the dosing sequence has been corrected.

Work is ongoing to determine the implications of the sequencing errors in the 160mg Q2W and 80mg Q4W arms. Based on ACELYRIN’s review to date and the fact that the placebo and 160mg QW arms were designed for consistent weekly dosing, the Company has no reason to believe the 160mg QW and placebo arms are impacted.

Next Steps

ACELYRIN’s wide-ranging review of the ongoing izokibep trials, including operational execution by the CRO, is continuing. ACELYRIN will contract with a third-party to conduct an independent audit of the trials being conducted by the CRO for ACELYRIN, including the HS trial and the PsA trial. ACELYRIN will not use this CRO for any new trials that it conducts. 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.

Pending completion of the evaluation from the third-party auditor, ACELYRIN plans to report top-line data from its PsA trial in the first quarter of 2024.

The Company previously presented differentiated 16- and 46-week data up to 80mg every other week from a Phase 2 trial of izokibep in PsA that was not conducted by the CRO. These results demonstrated dose-ordered responses as early as one month into treatment and increasing over time. Long-term efficacy results from the same trial presented recently at the American College of Rheumatology annual meeting showed that with longer duration of treatment, patients experienced durable and deepening resolution of disease across clinical manifestations of PsA, leading to further improvements in quality of life as measured by the Psoriatic Arthritis Impact of Disease questionnaire. Modeling from the Phase 2 PsA data predicted the potential for increased efficacy with higher doses over the 80mg Q2W. The ongoing PsA trial includes higher doses designed to evaluate the potential to further maximize responses for patients.

https://www.globenewswire.com/news-release/2023/11/27/2786538/0/en/ACELYRIN-INC-Provides-Update-on-Izokibep-Clinical-Development-Program.html