Photo Credit: AND-ONE

Patients with active psoriatic arthritis have shown significant efficacy results with izokibep.

Izokibep showed remarkable efficacy in patients with very active psoriatic arthritis (PsA) in a phase 2b/3 trial. The agent was well tolerated with a safety profile consistent with other IL-17A inhibitors.

Izokibep, a small protein therapeutic, has been designed to selectively inhibit IL-17A with high potency through tight binding affinity. “Izokibep is 1/10 of the size of a monoclonal antibody. It may penetrate difficult-to-access tissue domains better,” Prof. Philip Mease, MD, from the University of Washington, Swedish Medical Center, explained.

The main objective of the current phase 2b/3 study (NCT05623345) was to evaluate the efficacy and safety of izokibep through week 16 in patients with active PsA. Eligible participants of this randomized, double-blind, placebo-controlled trial had adult-onset active PsA (i.e. ≥6 months duration and ≥3 tender/swollen joints) with an inadequate response, intolerance, or contraindication to NSAIDs, cDMARDs, and/or TNF blockers. Participants were randomly assigned to receive either izokibep 160 mg every 2 weeks, izokibep 160 mg every week, or 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 participants on izokibep even achieved ACR70. Skin lesions cleared in about 50% of participants, reflecting the importance of this mechanism in skin disease. “A substantial number of patients achieved minimal disease activity [about 42% and 41% in the active arms versus 14% in the placebo group] according to our pretty stringent criteria,” Prof. Mease said.

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

According to these results, izokibep has the potential to offer deep clinical efficacy across multiple PsA domains, Prof. Mease concluded.