MoonLake Immunotherapeutics announced mixed results from its pivotal Phase 3 VELA program evaluating sonelokimab, an investigational nanobody targeting IL-17A and IL-17F, in patients with moderate-to-severe hidradenitis suppurativa (HS). While the combined program showed statistical significance across all endpoints, individual trial results revealed challenges that may complicate the regulatory pathway.
Trial Design and Patient Population
The VELA program enrolled 838 patients across two identical Phase 3 trials, VELA-1 and VELA-2, representing the first Phase 3 program to use the higher clinical response threshold of HiSCR75 as the primary endpoint. This endpoint requires at least a 75% reduction in abscess and inflammatory nodule count with no increase in abscess or draining tunnel count from baseline.
The trials compared a single 120mg dose of sonelokimab administered subcutaneously to placebo, with the primary endpoint assessed at week 16. Patient demographics were generally consistent between trials, with mean ages ranging from 36-38 years and approximately 53-62% female participants across treatment arms.
Efficacy Results Show Promise Despite Statistical Challenges
In the combined VELA program analysis, sonelokimab demonstrated statistically significant improvements across all primary and key secondary endpoints with p-values below 0.001. Using the pre-specified treatment policy strategy, 35.4% of patients treated with sonelokimab achieved HiSCR75 at week 16 compared to 21.6% on placebo.
VELA-1 met its primary endpoint with statistical significance, achieving a 17 percentage-point difference between sonelokimab (34.8%) and placebo (17.5%) for HiSCR75 response (p<0.001). The placebo response rate in VELA-1 fell within the expected historical range of 13-18%.
However, VELA-2 faced challenges due to an unexpectedly high placebo response rate of 25.6%, compared to 35.9% for sonelokimab, resulting in a delta of only 9% that failed to reach statistical significance using the composite strategy (p=0.053). Prof. Kristian Reich, Founder and Chief Scientific Officer at MoonLake, acknowledged the disappointment but emphasized the consistent performance of sonelokimab across both studies.
Secondary Endpoints Demonstrate Broad Clinical Benefit
Both trials achieved statistical significance for all key secondary endpoints using the treatment policy strategy. Approximately 30% of patients experienced meaningful pain reduction, defined as at least a 3-point improvement in worst pain numerical rating scale, in both VELA-1 and VELA-2 (p≤0.002).
Quality of life improvements were substantial, with nearly 60% of patients achieving a meaningful 4-point or greater improvement in Dermatology Quality of Life Index (DLQI), representing approximately a 20 percentage-point benefit over placebo (p≤0.001). The HS-specific Quality of Life score (HiSQOL) also showed consistent improvement across both trials (p<0.001).
Safety Profile Remains Favorable
Sonelokimab continued to demonstrate a favorable safety profile consistent with previous studies, with no new safety signals detected. Notably absent were key events of interest associated with IL-17A and F therapies, including suicidal ideation and behavior, hepatic events, inflammatory bowel disease, and serious infections.
The most frequent treatment-emergent adverse events were nasopharyngitis (8.6% vs 10.0% placebo), headache (4.8% vs 5.0% placebo), and upper respiratory tract infections (4.3% vs 7.5% placebo). Serious adverse events occurred in 2.5% of sonelokimab-treated patients compared to 1.8% on placebo.
Regulatory Path Forward and Pipeline Development
The company plans to discuss these interim results with regulatory authorities, including analytical strategies to address the higher-than-expected placebo response in VELA-2 and potential pathways for Biologics License Application submission. The VELA program will continue to its pre-specified 52-week readout in Q2 2026.
MoonLake's broader development program remains on track with multiple catalyst opportunities ahead. The Phase 2 LEDA trial in palmoplantar pustulosis is expected to report primary endpoint results in Q4 2025, followed by the Phase 2 S-OLARIS trial in axial spondyloarthritis in Q1 2026. The Phase 3 VELA-TEEN trial in adolescent HS and the Phase 3 IZAR program in psoriatic arthritis are both expected to report in H1 2026.
Market Opportunity and Unmet Need
Hidradenitis suppurativa affects an estimated 2% of the population, with three times more females affected than males. Real-world data indicates at least 2 million unique patients have been diagnosed and treated for HS in the US between 2016 and 2023, with the market opportunity projected to reach $15 billion by 2035.
The condition manifests as painful inflammatory skin lesions typically around the armpits, groin, and buttocks, with uncontrolled inflammation leading to irreversible tissue destruction and scarring. HS has a profound negative impact on quality of life, with higher morbidity than other dermatologic conditions, highlighting the significant unmet medical need that sonelokimab aims to address.
