Acelyrin, Inc. (Nasdaq: SLRN) has announced positive top-line results from its global Phase 2b/3 clinical trial of izokibep in psoriatic arthritis (PsA). The study met its primary endpoint, demonstrating a statistically significant improvement in ACR50 at 16 weeks compared to placebo, marking a potential advancement in the treatment of this chronic inflammatory disease.
The Phase 2b/3 trial (NCT05623345) was a global, multi-center, randomized, double-blind, placebo-controlled study involving 351 adult patients with active PsA across 71 sites in the United States and Europe. Patients were randomized to receive subcutaneous doses of izokibep at 160 mg weekly (QW), 160 mg every other week (Q2W), or 80 mg every four weeks (Q4W), or placebo.
Robust Efficacy and Favorable Safety Profile
The 160 mg QW and Q2W arms of the trial demonstrated improved magnitude of responses on higher hurdle endpoints such as ACR70 and PASI100, as well as composite endpoints ACR50/PASI100 and Minimal Disease Activity, relative to the Phase 2 80 mg Q2W dose. Notably, this was achieved despite a higher baseline disease burden in the Phase 2b/3 trial population compared to the Phase 2 trial.
Izokibep was well-tolerated, with a favorable safety profile consistent with previous experience and the IL-17A class. The trial had a low study discontinuation rate of less than 3%. Mild-to-moderate injection site reactions (ISRs) were observed, with discontinuations due to ISR occurring in less than 2% of patients. There were two cases of mild candida infection – one in the placebo arm and one in the 160 mg QW arm – and no cases of suicidal ideation or behavior were reported.
Potential Differentiation in Enthesitis Resolution
Pre-specified analyses suggest potential differentiation in enthesitis resolution. While enthesitis resolution overall was not statistically significant due to a high placebo response, izokibep achieved clinically meaningful resolution in patients with the highest burden of enthesitis (baseline Leeds Enthesitis Index (LEI) 3-6) relative to placebo. This effect has not been previously reported by other agents.
Expert Commentary
"These positive Phase 2b/3 data reinforce the potential demonstrated in Phase 2 for izokibep to provide meaningful benefit in treating the debilitating signs and symptoms of active psoriatic arthritis in the joints and skin, as well as enthesitis where the results in the most severe patients are encouraging and warrant further study," said Philip Mease, MD, MACR, Director of Rheumatology Research at Swedish Medical Center. "We have observed from the Phase 2 46-week data that there is no safety limitation to long-term treatment with izokibep and that longer duration of therapy demonstrated the potential for even further improvements over time."
Implications for Psoriatic Arthritis Treatment
Psoriatic arthritis affects an estimated 30% of the 125 million people living with psoriasis worldwide. The positive results from this Phase 2b/3 trial suggest that izokibep could offer a valuable new treatment option for patients with PsA, particularly those with significant enthesitis. The drug's favorable safety profile and potential for higher clinical responses compared to existing IL-17A inhibitors further support its development as a potential new medicine for patients.
