Sonelokimab, a novel IL-17A- and IL-17F-inhibiting nanobody for the treatment of moderate-to-severe hidradenitis suppurativa: a global, randomized, double-blind, placebo-controlled phase 2 clinical trial (MIRA)

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic disabling and debilitating inflammatory disease with limited therapeutic options. OBJECTIVE: To present the primary results of the phase 2 MIRA trial, which evaluated the efficacy and safety of the IL-17A- and IL-17F-inhibiting nanobody sonelokimab in adults with moderate-to-severe HS. METHODS: MIRA was a 24-week global, randomized, prospective, parallel-group, double-blind, placebo-controlled trial. Eligible patients were randomized (2:2:2:1) to receive subcutaneous sonelokimab 120 mg, sonelokimab 240 mg, placebo, or adalimumab (active reference arm). The primary endpoint was the proportion of patients achieving HS Clinical Response 75 (HiSCR75) versus placebo at week 12 using non-responder imputation in an intention-to-treat population. RESULTS: Two hundred thirty-four patients were randomized (sonelokimab 120 mg, n=67; sonelokimab 240 mg, n=66; placebo, n=68; adalimumab active reference arm, n=33). The primary endpoint of HiSCR75 was met for both sonelokimab doses (120 mg: 43%, P<0.001; 240 mg: 35%, P=0.007) versus placebo (15%). Responses increased or were maintained through week 24. No new safety signals were identified. LIMITATIONS: MIRA was a 24-week study; ongoing phase 3 trials will assess longer-term efficacy and safety. CONCLUSIONS: Sonelokimab demonstrated high levels of clinical response in patients with moderate-to-severe HS and was well tolerated.