ACHIEVEMENT OF DIFFERENT TREATMENT TARGETS WITH IZOKIBEP DEMONSTRATES EFFICACY BENEFITS IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS: RESULTS FROM A 16-WEEK RANDOMIZED, PLACEBO-CONTROLLED PHASE 2 CLINICAL TRIAL
Authors: Behrens F et al.
Different IL-17 inhibitors are approved in psoriatic arthritis and have demonstrated efficacy in resolution of arthritis, enthesitis, spondylitis, dactylitis, skin and nail involvement. Izokibep represents a first-in-class fusion protein that binds IL-17 with high potency. Because of its small molecular size (18.6 kD versus monoclonal antibodies with around 150 kD) it might access target structures more easily than anti-IL17 directed monoclonal antibodies. This may theoretically result in improved efficacy. In this phase 2 multicenter, randomized and placebo-controlled clinical trial izokibep was used at 40mg or 80mg subcutaneously every 2 weeks. Efficacy was assessed over a range of clinical outcome parameters over 16 weeks with the ACR50 response being the primary endpoint. 135 patients were randomized, had a mean DAS28-CRP of 4.51 and a mean DAPSA score of 46.8 at baseline. ACR50 at week 16 was achieved significantly more frequent with Izokibep (48% in the 40mg group and 52% in the 80mg group) versus placebo (13%). DAS28-CRP already differed between Izokibep and placebo within 2 weeks after treatment initiation. 83% (40mg) and 85% (80mg) of patients achieved a PASI75 response versus 14% placebo patients. No new safety signals were observed and event rates were mostly similar between all treatment groups.
Do we need another kid on the playground? The concept of a smaller molecule that binds IL-17 with high affinity is intriguing and may theoretically result in better efficacy results. The trial presented is a phase 2 trial and definitely too small to test this hypothesis but may form the basis for future exploration. It might be interesting to see whether reactivation of IBD remains an issue with izokibep – if not, this might open up a new venue.