Izokibep Data from Psoriatic Arthritis, Hidradenitis Suppurativa Support Phase 3 Development

With excitement already building around its potential in treatment algorithms for hidradenitis suppurativa (HS), topline data from a global phase 2b/3 trial of izokibep indicate the agent may be poised for an entry into management of psoriatic arthritis (PsA) in the future.

On March 11, 2024, Acelyrin Inc. announced topline data from the phase 2b/3 trial, which examined use of the IL-17A inhibitor in patients with psoriatic arthritis, suggested izokibep 160 mg in weekly and every 2 weeks dosing met the primary endpoint of ACR50 at 16 weeks versus placebo with high statistical significance. The same day, Acelyrin also announced long-term data from the open-label extension portion of their phase 2b trial of the agent in HS.^1,2

“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.² “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.”

Building on 16-week data, the HS results announced by Acelyrin on March 11 offered insight into the open-label extension period of the phase 2b trial. Results from the analysis of long-term data demonstrate use was associated with dose ordered and robust improvements in Hidradenitis Suppurativa Clinical Response (HiSCR), with about a third of patients achieving HiSCR100 or resolution of abscesses and nodules, by week 16 and through week 32. Additionally, the release details evidence suggesting those who switched from placebo to izokibep at week 16 experienced a comparable speed and magnitude of response as those beginning treatment with izokibep at baseline for HiSCRs, draining tunnels, skin pain and Dermatology Life Quality Index.¹

As mentioned by Mease, the topline data announced from the phase 2b/3 trial in PsA on March 11 adds to the understanding offered by positive data from a phase 2 trial of the agent in PsA. Published in the British Journal of Dermatology in September 2023, the phase 2 trial assessed use of izokibep 2, 20, 80 or 160 mg every 2 weeks for 12 weeks against placebo therapy.^2,3

Following this 12-week treatment course, patients given placebo were switched to izokibep 80 mg, and dosing intervals were adapted based on Psoriasis Area and Severity Index (PASI) scores for all patients. This portion of the trial was followed by a pair of optional, consecutive 1-year extension periods for a total study duration of 3 years.³

The primary outcome of interest in the phase 2 trial was a 90% reduction in PASI score (PASI 90) at week 12. A total of 106 individuals were included in the full analysis set from the trial. Among this cohort, PASI 90 response rates at week 12 were 0%, 5%, 19%, 71% and 59% for the placebo, 2-, 20-, 80- and 160-mg izokibep groups, respectively.³

The global phase 2b/3 trial is a randomized, double-blind, placebo-controlled trial of 351 adult patients with PsA and conducted at 71 sites in the US and Europe. The trial randomized patients to subcutaneous izokibep 160 mg every week, 160 mg every 2 weeks, 80 mg every 4 weeks, or placebo.²

The trial’s results indicated use of izokibep was associated with a statistically significant improvement in ability to achieve ACR50 at week 16 relative to placebo therapy. Results also indicated those in the 160 mg weekly and every 2 weeks arms showed improved magnitude of responses for ACR70, PASI100, and Minimal Disease Activity relative to the phase 2 trial’s 80 mg every 2s week dosing group, which the release points out occurred despite a greater baseline disease burden in the phase 2b/3 trial population.²

Safety analyses of the trial suggested izokibep was well-tolerated with a safety profile consistent with previous data and the IL-17A class, with no evidence of the safety liabilities observed with targeting IL-17A&F. The rate of study discontinuation was less than 3%, with discontinuations due to injection site reactions occurring in less than 2% of the trial population. The release called attention to 2 cases of mild candida, with one occurring in the placebo and 160 mg once weekly arm, and no instances of suicidal ideation/behavior.²

The release from Acelyrin highlighted izokibep achieved clinically meaningful resolution in patients with the highest burden of enthesitis relative to placebo, which has not been observed with other agents. Based on data from the phase 2b/3 trial, Acelyrin expressed plans for the potential initiation of a confirmatory phase 3 trial by the end of 2024, which is also when the company is expecting phase 3 data from izokibep’s ongoing HS program.^1,2

“We are excited about our continued progress with izokibep in both PsA and HS,” said Shao-Lee Lin, MD, PhD, founder and chief executive officer of ACELYRIN.² “The positive PsA study results at week 16 and the magnitude of responses give us conviction that 160 mg Q2W delivers higher clinical responses than those reported by the approved IL-17A agents, and responses comparable to those reported by the IL-17A&F agents without the associated safety liabilities. Across indications, we have observed clinically meaningful and potentially differentiated benefit from izokibep. We have consistently seen responses in high order efficacy measures such as ACR70 and PASI100 in PsA and HiSCR100 in HS that move patients toward disease resolution. This reinforces our enthusiasm for developing izokibep as an important potential new medicine for patients.”

References:

1. ^{Acelyrin, Inc.. announces long-term 32-week data from the phase 2B trial of Izokibep in Hidradenitis Suppurativa demonstrating sustained responses and deepening clinical benefit - improving quality of life for patients. ACELYRIN, INC. March 11, 2024. Accessed March 14, 2024. https://investors.acelyrin.com/news-releases/news-release-details/acelyrin-inc-announces-long-term-32-week-data-phase-2b-trial.}
2. ^{Acelyrin, Inc.. announces positive top-line results from its Global Phase 2B/3 clinical trial of Izokibep in psoriatic arthritis. ACELYRIN, INC. March 11, 2024. Accessed March 14, 2024. https://investors.acelyrin.com/news-releases/news-release-details/acelyrin-inc-announces-positive-top-line-results-its-global.}
3. ^{Gerdes S, Staubach P, Dirschka T, et al. Izokibep for the treatment of moderate-to-severe plaque psoriasis: a phase II, randomized, placebo-controlled, double-blind, dose-finding multicentre study including long-term treatment. Br J Dermatol. 2023;189(4):381-391. doi:10.1093/bjd/ljad186}