MoonLake Shares Findings from Dual Phase 3 Trials of Sonelokimab

MoonLake Immunotherapeutics has reported week 16 interim findings from its 2 phase 3 VELA trials (VELA-1 (NCT06411899) and VELA-2 (NCT06411379)), evaluating the investigational nanobody sonelokimab in adults with moderate to severe hidradenitis suppurativa (HS). The results provide the first phase 3 dataset to use HS Clinical Response (HiSCR) 75, a more stringent endpoint than the traditionally applied HiSCR50, as the primary outcome.¹

Key Efficacy Findings

Across the combined VELA program (n=838), the company stated sonelokimab demonstrated a clinically meaningful and statistically significant benefit at week 16 across primary and key secondary endpoints when analyzed under both pre-specified statistical strategies. Using the treatment policy strategy, HiSCR75 response rates were 35.4% for sonelokimab versus 21.6% for placebo (p<0.001).

• VELA-1: Sonelokimab achieved HiSCR75 in 34.8% compared with 17.5% for placebo (p<0.001).
• VELA-2: HiSCR75 was achieved in 35.9% versus 25.6% for placebo (p=0.033).

Notably, while VELA-1 met significance under both analytic strategies, VELA-2 did not achieve statistical significance for the primary endpoint using the composite strategy (p=0.053), which the company noted is in part due to a higher-than-expected placebo response.

Secondary endpoints, including HiSCR50, IHS4-55 reduction, Dermatology Life Quality Index (DLQI), HiSQOL, and ≥3-point pain NRS reduction, showed consistent, statistically significant improvements with sonelokimab across both trials. Approximately 30% of patients experienced marked pain reduction by week 16, and nearly 60% achieved a meaningful DLQI improvement (≥4-point reduction).

Safety Profile

Sonelokimab maintained a favorable safety profile, consistent with earlier trials. Treatment-emergent adverse events (TEAEs) occurred in 67.3% of sonelokimab patients versus 55.6% in placebo. Most TEAEs were mild to moderate.

• Common TEAEs included nasopharyngitis, headache, and upper respiratory tract infections.
• Oral candidiasis occurred in 7.3% of patients receiving sonelokimab versus 0.4% on placebo.
• No new safety signals were observed, including no cases of suicidal ideation, hepatic events of concern, or major adverse cardiovascular events.

Discontinuation due to adverse events was low (2.9% in sonelokimab vs. 1.4% in placebo).

Trial Design and Methodology

The VELA-1 and VELA-2 trials are large, identically designed, global, randomized, placebo-controlled phase 3 studies. Patients received a 120 mg subcutaneous dose of sonelokimab or placebo every other week through week 6, followed by monthly maintenance dosing. At week 16, placebo patients crossed over to active treatment.

The primary endpoint (HiSCR75) required ≥75% reduction in abscess and inflammatory nodule count without worsening of draining tunnels. Secondary endpoints included HiSCR50, DLQI, HiSQOL, IHS4-55, and patient-reported pain outcomes.

Clinical Implications

These interim findings suggest that dual IL-17A/F inhibition with sonelokimab may offer a promising therapeutic approach in HS, a disease with substantial unmet need and limited treatment options. The high placebo response in VELA-2 underscores challenges in HS trial design, particularly regarding variability in patient-reported outcomes and disease fluctuation.

For clinicians, the results highlight:

• Early and sustained efficacy signals, with improvements observed as early as week 4.
• Consistency across lesion-based metrics and quality-of-life measures.
• Manageable safety profile without unexpected adverse effects.

Broader Context

Outside the clinical community, the VELA-2 outcome has had significant financial consequences. On September 29, 2025, MoonLake shares (NASDAQ: MLTX) fell by nearly 90% in a single day after disclosure that the VELA-2 trial did not achieve statistical significance under the composite strategy. In response, Hagens Berman, a US shareholder rights firm, announced an investigation into whether MoonLake may have misled investors regarding trial design, particularly the handling of intercurrent events and expectations around HiSCR75 performance.²

Next Steps

Both trials will continue through week 52, after which patients may enter a long-term open-label extension. MoonLake has indicated plans to engage regulators regarding a potential registration pathway for HS. Additional trials are ongoing in adolescent HS (VELA-TEEN), psoriatic arthritis (IZAR program), palmoplantar pustulosis (LEDA), and axial spondyloarthritis (S-OLARIS).

Conclusion

The week 16 VELA results position sonelokimab as a potentially important addition to the therapeutic landscape for HS. While longer-term data and regulatory review remain pending, these findings support continued investigation of IL-17A/F inhibition as a targeted strategy in managing this debilitating disease.

References

1. MoonLake Immunotherapeutics reports on week 16 results of the VELA phase 3 hidradenitis suppurativa program with the nanobody sonelokimab. News release. MoonLake Immunotherapeutics. Published September 28, 2025. Accessed October 1, 2025. https://www.globenewswire.com/news-release/2025/09/28/3157370/0/en/MoonLake-Immunotherapeutics-reports-on-week-16-results-of-the-VELA-Phase-3-hidradenitis-suppurativa-program-with-the-Nanobody-sonelokimab.html
2. MoonLake Immunotherapeutics (MLTX) faces investor scrutiny after reporting disappointing phase 3 trial data for lead drug candidate. News release. Hagens Berman. Published October 1, 2025. Accessed October 1, 2025. https://www.prnewswire.com/news-releases/moonlake-immunotherapeutics-mltx-faces-investor-scrutiny-after-reporting-disappointing-phase-3-trial-data-for-lead-drug-candidate----hagens-berman-302571989.html