Acelyrin’s lead asset Izokibep is a small protein therapeutic engineered to selectively inhibit IL-17A with high potency due to its strong binding affinity.

In Phase IIb/III Study (NCT05623345), a total of 343 patients were enrolled in the study, with 113 receiving izokibep 160 mg every two weeks (Q2W), 112 receiving izokibep 160 mg once a week (QW), and 118 receiving placebo their average age was 51 years, BMI was 30 kg/m2, and the duration since diagnosis was 7 years, with 53% being male. Baseline disease characteristics were generally balanced across the treatment groups. The primary goal of achieving a 50% improvement in American College of Rheumatology criteria (ACR50) by Week 16 was met, with significantly higher percentages of patients achieving ACR50 with izokibep Q2W (43%) and QW (40%) compared to placebo (15%), showing improvement as early as week 4.

Moreover, more patients receiving izokibep, regardless of dosing frequency, achieved other key treatment goals such as ACR70, complete skin clearance (PASI100), and minimal disease activity (MDA). Patients on izokibep also demonstrated clinically meaningful improvements in Health Assessment Questionnaire Disability Index (HAQ-DI) scores compared to those on placebo. Subgroup analyses revealed significant reductions in enthesitis (inflammation where tendons or ligaments insert into bones) with izokibep compared to placebo, especially in patients with high baseline enthesitis burden.

Regarding safety, treatment-emergent adverse events (AEs) were observed in 66%, 72%, and 41% of patients receiving izokibep Q2W, izokibep QW, and placebo, respectively. The most common AEs were related to injection sites, mostly mild to moderate in severity, and rarely led to treatment discontinuation. Serious AEs were reported at low rates across all groups, and incidences of ulcerative colitis and candidiasis were also low. No deaths, uveitis cases, or reports of suicidal ideation were documented during the study.

KOL Insight

“In Phase II, the enthesitis data looked really good; in Phase III, the enthesitis data looks the same as for any other IL-17 inhibitor.”- MBChB, PhD, UK

Conclusion:

Targeting IL-17A effectively with Izokibep may offer a favorable balance of heightened therapeutic effectiveness without introducing new safety concerns. The potent activity and compact size of Izokibep could significantly influence clinical outcomes.

The success of Izokibep in PsA marks a significant achievement for Acelyrin, especially following its setback in a Phase IIb/III trial for Hidradenitis Suppurativa (HS). Compared to the Phase II trial, where a lower dose of 80 mg every other week was used, the 160 mg weekly and every other week doses of Izokibep showed improved responses across various endpoints, such as ACR70, PASI100, and minimal disease activity. Acelyrin plans to submit two registrational trials to support Izokibep's application, indicating confidence in its potential.

However, Acelyrin faces competition in the PsA market, particularly from Bimekizumab, as evidenced by UCB's Phase III data presentation at EULAR. Bimekizumab demonstrated consistent and durable efficacy in PsA patients, regardless of prior treatment with biologic disease-modifying antirheumatic drugs (bDMARDs), suggesting strong competition for Izokibep in this therapeutic area.

Despite the setback in the HS clinical trial, Acelyrin's diversified pipeline positions the company well for multiple market opportunities. Strategic initiatives in high-need areas like uveitis and Axial Spondyloarthritis (AxSpA) reflect a proactive approach to addressing unmet medical needs and leveraging market momentum in PsA.