Novel IL-17A Blocker Continues to Impress in PsA

Derick Alison
Derick Alison
6 Min Read

SAN DIEGO — The triple-action investigational agent known as izokibep was highly effective against psoriatic arthritis (PsA) over 46 weeks in a new analysis of the product’s first phase II trial, a researcher said here.

Following a 2022 report on izokibep’s performance with 16 weeks of treatment, the presentation this week at the American College of Rheumatology’s (ACR) annual meeting indicated that the drug has a bright future once the dosing is settled.

As reported by Philip Mease, MD, of the University of Washington in Seattle, responses by several measures continued to improve when treatment with the interleukin-17A inhibitor continued for an additional 30 weeks beyond the initial 16. Rates of complete skin clearance topped 70% and resolution of enthesitis, which was already common at week 16, remained the rule through week 46 with the highest drug dose and rose steadily for patients receiving a lower dose.

Izokibep was designed to improve on existing drugs such as secukinumab (Cosentyx) that block IL-17A. It’s still a protein but it’s one-tenth the size of a monoclonal antibody. Mease said this is expected to help it penetrate tissues better. Also, unlike other agents, it binds to both subunits of IL-17A and also to serum albumin, which extends its half-life in circulation.

The placebo-controlled phase II study randomized 135 patients to placebo or one of two izokibep doses, 40 and 80 mg, given by injection every 2 weeks. Outcomes for the primary analysis were analyzed at week 16. The trial was originally designed to extend out to week 46, with the placebo group then switched at week 16 to the 80-mg izokibep dose.

However, Mease explained, the commercial sponsor terminated the trial once all patients had their 16-week evaluations, believing there was enough data to move forward with a more advanced trial. By that point, close to half the participants had already reached week 46, and Mease’s group was given permission to analyze and report the longer-term findings in that subgroup totalling 59 patients.

Efficacy outcomes included ACR50 and ACR70 response rates (that is, 50% and 70% improvement according to established ACR criteria), 100% reduction in Psoriasis Area and Severity Index score (PASI100), two measures specific to PsA, and two evaluations of enthesitis.

Highlights were as follows:

  • ACR70 rates, which stood at 20% at week 16 in the 80-mg group, subsequently hit 52% by week 46. In the original placebo group, which saw an ACR70 rate of 5% at week 16, this endpoint was reached by a whopping 67% in the final evaluation.
  • Some 57% of patients assigned to 80 mg achieved minimal PsA disease activity at week 46, up from 39% at week 16.
  • PASI100 response rates at week 46 were 71% with 80 mg izokibep throughout the trial, and 73% in the placebo group that switched to 80 mg.
  • At week 16, enthesitis resolution according to Leeds Enthesitis Index scoring was achieved by 88% of patients on 80 mg, so there was not much room for improvement. Still, Mease noted that this was maintained through week 46 (89%), and more patients on the 40-mg dose achieved full resolution as time went on — from 67% at week 16 to 83% at week 46.

The week 16 evaluations found little difference or consistency in efficacy between the two izokibep doses, with the lower dose showing better results on some measures. At week 46, though, there was clearer separation with the 80-mg dose evidently superior. Mease said a follow-on phase IIb/III trial is now underway that will test 80 and 160 mg in an attempt to push the efficacy even further.

This higher dose was justified in large part by the lack of concerning adverse effects seen in the current study. Events through week 16 were similar between placebo and both active-drug doses, and nothing occurred in the subsequent 30 weeks to raise alarm. Injection-site reactions were common but, overall, izokibep’s safety profile seems “generally consistent with other IL-17A inhibitors,” Mease said.

Results from the phase IIb/III trial are expected by the end of next year.

  • author['full_name']

    John Gever was Managing Editor from 2014 to 2021; he is now a regular contributor.

Disclosures

The study was funded by Acelyrin with additional support from Affibody. Mease and other authors reported extensive relationships with industry. Several authors were employees of Acelyrin and Affibody.

Primary Source

American College of Rheumatology

Source Reference: Mease PJ, et al “Izokibep demonstrates major disease control on ACR70, PASI100, and enthesitis resolution in patients with active psoriatic arthritis treated through 46 weeks” ACR 2023; Abstract 1688.

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