Sonelokimab, an IL-17A/IL-17F-inhibiting nanobody for active psoriatic arthritis: a randomized, placebo-controlled phase 2 trial
Iain B. McInnes, Laura C. Coates, Philip J. Mease, Alexis Ogdie, Arthur Kavanaugh, Lihi Eder, Georg Schett, Alan Kivitz, Dennis McGonagle, Nuala Brennan, A. Godwood, Eva Cullen, Kristian Reich, Christopher T. Ritchlin, Joseph F. Merola
Abstract
Psoriatic arthritis (PsA) is a progressive, multidomain and interleukin-17 (IL-17)-linked disease that results in substantial quality-of-life deficits. Thereby, we conducted a phase 2 randomized, double-blind, placebo (PBO)-controlled trial of sonelokimab (SLK), a nanobody that binds with a similarly high affinity to IL-17A and IL-17F, inhibiting all dimers. Overall, 207 patients with active PsA were randomized to SLK 120-mg or 60-mg every 4 weeks (Q4W; both with induction (WI)), or to 60-mg Q4W with no induction, PBO or adalimumab (reference arm). The primary endpoint of American College of Rheumatology (ACR) 50 at week 12 was met for SLK 60-mg and 120-mg WI (60-mg WI = 46.3% (19/41; odds ratio (OR) = 3.6; 95% confidence interval (CI) = 1.3-9.9; P < 0.05); 120-mg WI = 46.5% (20/43; OR = 4.0; 95% CI = 1.4-11.3; P < 0.01) versus PBO = 20.0% (8/40)). SLK resulted in significant benefits across the key secondary endpoints of ACR20 (60-mg WI = 78.0% (32/41; P < 0.001) and 120-mg WI = 72.1% (31/43; P = 0.002) versus PBO = 37.5% (15/40)) and Psoriasis Area and Severity Index (PASI) 90 at week 12 (60-mg WI = 76.9% (20/26; P < 0.001) and 120-mg WI = 59.3% (16/27; P = 0.003) versus PBO = 15.4% (4/26)). Robust responses were observed among patients randomized to SLK at week 24 for the high-threshold composite endpoints of ACR70 + PASI 100 (exploratory) and minimal disease activity (secondary), achieved by up to 48% (13/27; 120-mg WI) and 61% (25/41; 60-mg WI), respectively. SLK was well-tolerated; the most common treatment-emergent adverse events were nasopharyngitis (60 mg = 6.1%; 120 mg = 5.2%), upper respiratory tract infection (60 mg = 6.1%; 120 mg = 4.1%), injection-site erythema (60 mg = 3.7%; 120 mg = 3.1%) and headache (60 mg = 2.4%; 120 mg = 4.1%). Four cases of mild to moderate oral candidiasis occurred (60 mg = 2.4%; 120 mg = 2.1%). Overall, SLK delivered substantial improvements in the signs and symptoms of PsA across various outcomes and domains. ClinicalTrials.gov registration: NCT05640245 .