Small protein targeting IL-17A effective in PsA management

The novel protein therapeutic izokibep has shown remarkable efficacy in a phase 2b/3 trial, significantly improving symptoms in patients with active psoriatic arthritis (PsA). The agent not only reduced joint inflammation but also cleared skin lesions in a substantial number of patients.

Despite several available treatments, an unmet need exists for therapies demonstrating efficacy across multiple disease manifestations, including arthritis, enthesitis, and psoriasis in patients with active PsA [1,2]. Izokibep, a small protein therapeutic, has been designed to selectively inhibit IL-17A with high potency through tight binding affinity. “Izokibep is one-tenth of the size of a monoclonal antibody. It may penetrate difficult-to-access tissue domains better,” Prof. Philip Mease (University of Washington; Swedish Medical Center, WA, USA) explained [3].

The main objective of the current randomised, double-blind, placebo-controlled, phase 2b/3 study (NCT05623345) was to evaluate the efficacy and safety of izokibep through week 16 in patients with active PsA. Eligible participants had adult-onset active PsA (i.e. ≥6 months duration and ≥3 tender/swollen joints) with an inadequate response, intolerance, or contraindication to NSAIDs, conventional DMARDs, and/or TNF blockers. The participants were randomly assigned to izokibep 160 mg every 2 weeks, izokibep 160 mg every week, or a placebo every week. The primary endpoint was achieving a 50% improvement in the American College of Rheumatology criteria (ACR50) at week 16.

Data from 343 participants could be included in the analysis. Baseline disease characteristics were balanced across all groups. “Patients had very active disease and longstanding PsA,” Prof. Mease said.

By week 16, a higher percentage of participants receiving izokibep every 2 weeks (43%) and every week (40%) achieved ACR50 compared with those on placebo (15%; P<0.0001 for each comparison), with improvements noted as early as week 4. A quarter of the participants on izokibep even achieved ACR70. Skin lesions cleared in about 50% of the participants, reflecting the importance of the IL-17 pathway in skin disease. “A substantial number of patients achieved minimal disease activity [about 42% and 41% in the active arms vs 14% in the placebo group] according to our pretty stringent criteria,” Prof. Mease said. In the prespecified analysis, enthesitis resolution was achieved by 45% and 56% on izokibep weekly and every other week dosing, compared with 47% on placebo.

Most adverse events were mild-to-moderate injection site reactions, leading to discontinuation in only a small percentage of cases. Serious adverse events were infrequent, with 2 cases of candidiasis and 1 case of inflammatory bowel disease in each active arm.

“We're going to be pursuing this further with longer-term extension into phase 3,” Prof. Mease concluded.

1. Zardin-Moraes M, et al J Rheumatol 2020:47:839-46.
2. Singla S, et al. RMD Open 2024;10:e003809.
3. Mease PJ, et al. Efficacy and safety of izokibep in patients with active psoriatic arthritis: Week 16 results from a Phase 2B/3 study. LBA0005, EULAR 2024 Congress, 12–15 June, Vienna, Austria.

Copyright ©2024 Medicom Medical Publishers



Posted on 29 July 202429 July 2024