FDA Feedback Supports BLA Pathway for Sonelokimab in HS

Despite advances in biologic therapy, treatment options for hidradenitis suppurativa (HS) remain limited, and many patients experience inadequate or partial responses.¹ With this in mind, MoonLake Immunotherapeutics has provided an update on the regulatory status and clinical evidence supporting sonelokimab (SLK), an investigational biologic therapy, following a recent type B meeting with the US FDA.²

Sonelokimab has been evaluated in 3 key clinical trials in moderate to severe HS: MIRA, VELA-1, and VELA-2. Collectively, these studies enrolled more than 1,000 patients and used similar randomized, placebo-controlled designs. A notable aspect of this development program is the use of HiSCR75 (HS Clinical Response with at least 75% reduction in abscess and inflammatory nodule count) as a primary endpoint, a more stringent outcome measure than the traditional HiSCR50 that is commonly used in HS trials.

The phase 2 MIRA trial was the first placebo-controlled randomized study in HS to use HiSCR75 as its primary endpoint. In this study, treatment with 120 mg of SLK resulted in a 43% HiSCR75 response rate at week 12, corresponding to a 29 percentage point difference versus placebo (p < 0.001). These findings suggested clinically meaningful efficacy over placebo using a high response threshold, although the trial duration was relatively short and primarily focused on induction efficacy.

The phase 3 VELA-1 and VELA-2 trials were designed to further evaluate the efficacy and safety of SLK in a larger population over a longer induction period. VELA-1 met its primary endpoint, with a HiSCR75 response rate of 35% at week 16 in the 120 mg SLK group, representing a 17 percentage point improvement over placebo (p < 0.001). Key secondary endpoints were also met with statistical significance across pre-specified analyses, reinforcing the robustness of the efficacy signal in this study.

VELA-2 yielded a more nuanced result. Using the pre-specified treatment policy estimand, SLK achieved statistical significance on the primary endpoint, with a 36% HiSCR75 response rate at week 16 and a 10 percentage point difference versus placebo (p = 0.033). However, a higher-than-anticipated placebo response limited the statistical significance under the primary composite analysis method, where the difference versus placebo was 9 percentage points (p = 0.053). This outcome underscores the challenges inherent in HS trials, including variability in placebo response and disease fluctuation, and highlights the importance of estimand selection and analytical strategy.

Across all 3 trials, SLK demonstrated a safety profile that was described as favorable and consistent, although detailed safety data, including adverse event rates and longer-term exposure outcomes, will be important for contextualizing benefit–risk, particularly as 52-week data from VELA-1 and VELA-2 become available.

Following the mixed but generally positive VELA readouts, MoonLake sought regulatory clarification via a type B meeting with the FDA. According to the company, the FDA indicated that substantial evidence of effectiveness (SEE) for SLK in HS may be established using the existing data from MIRA, VELA-1, and VELA-2, without the need for additional HS-specific clinical trials. This feedback suggests that the FDA considers the totality of evidence across these trials potentially sufficient for a biologics license application (BLA), provided that the analyses are appropriately presented and justified.

Importantly, the FDA advised that VELA-2 data should be included in the marketing application to inform the safety assessment, regardless of its role in establishing efficacy. The agency also clarified that mechanistic evidence cannot be used as confirmatory evidence in combination with a single clinical trial to establish SEE, reinforcing the need for clinical outcome data as the foundation of approval decisions.

Based on the official meeting records, MoonLake plans to proceed with BLA preparation, targeting submission in the second half of 2026. From a clinical perspective, this development program illustrates both the potential of higher-stringency endpoints such as HiSCR75 to demonstrate meaningful benefit and the ongoing complexities of interpreting heterogeneous trial results in HS. The forthcoming long-term data and regulatory review will be critical in determining the eventual clinical role of sonelokimab should it receive approval.

References

1. Garg A, Hsiao J, Porter ML, Shi V. Current treatments and future directions for hidradenitis suppurativa: a narrative review of completed and ongoing phase 3 clinical trials of biologic therapies. Dermatol Ther (Heidelb). 2025;15(9):2361-2377. doi:10.1007/s13555-025-01487-y
2. MoonLake Immunotherapeutics announces positive outcome from type B meeting with U.S. FDA and announces investor day. News release. Published January 8, 2026. Accessed January 8, 2026. https://www.globenewswire.com/news-release/2026/01/08/3215344/0/en/MoonLake-Immunotherapeutics-Announces-Positive-Outcome-from-Type-B-Meeting-with-U-S-FDA-and-Announces-Investor-Day.html