Expanding the IL-17 Therapeutic Landscape Save

IL-17 inhibitors are an effective therapeutic for a broad spectrum of inflammatory and autoimmune diseases and its blockade has revolutionized management of diseases such as psoriasis, psoriatic arthritis and SpA. Currently, four IL-17 inhibitors are approved, particularly for the management of moderate-to-severe plaque psoriasis and spondyloarthropathies. Secukinumab and Ixekizumab are both monoclonal antibodies directly targeting IL-17A. Brodalumab targets the IL-17A receptor and is only approved for psoriasis, and the new kid on the block, bimekizumab, a dual IL-17A/IL-17F inhibitor, is already showing promise for a variety of inflammatory conditions.

Is there a need for more medications within the same therapeutic class?

Abstract OP0102 presented the phase 3 results of Xeligekimab (a recombinant human IL-17A-neutralizing immunoglobulin) in ankylosing spondylitis. In this study, 465 Chinese patients showed that at week 16, a significantly higher proportion of patients in both doses (100 and 200mg) of the medication achieved the primary outcome with a sustained response. While this medication is already approved in China for psoriasis and psoriatic arthritis, this study broadens its use to AS.

Additionally, abstract OP0096 presented the phase 2 results of the ARGO trial, which evaluated sonelokimab, a novel IL-17A- and IL-17F-inhibiting nanobody in a multidomain outcome strategy for patients with psoriatic arthritis achieving its primary endpoint at week 12 with both doses (60mg and 120mg) as well as achieving significantly higher rates of ACR50 vs. placebo, with response rates further increasing through week 24. The novel nanobody technology seems to enhance efficacy given smaller molecular weight.

The benefits of having different drugs in the same class can allow for more personalized care given response to biologics differ between patients. Additionally, there is evidence that switching medications within the same class in patients with primary or even secondary failure can still induce response in both PsA and AS. Moreover, the larger number of alternatives can improve access given competitive pricing and lower risk of supply shortages. The design of new studies and novel mechanisms that improve efficacy allows for enhanced responses. Finally, it brings room to broaden indications such as the case of hidradenitis suppurativa or the ongoing trials in SLE and GCA.