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MoonLake's sonelokimab sustains deep responses in Phase III hidradenitis suppurativa trials at week 40

MoonLake Immunotherapeutics (Nasdaq: MLTX) reported Week 40 data from its Phase III VELA program evaluating sonelokimab in hidradenitis suppurativa, showing continued improvement in clinical responses beyond the Week 16 primary endpoint, with 62% of treated patients achieving HiSCR75 and up to 32% reaching complete clinical response as measured by HiSCR100.

The VELA Program and Trial Design

The VELA-1 and VELA-2 trials are identical, global, randomized, double-blind, placebo-controlled Phase III studies that enrolled a combined 838 adults with moderate-to-severe HS. Both trials used HiSCR75 — defined as at least a 75% reduction in abscess and inflammatory nodule count with no increase in abscess or draining tunnel count — as the primary endpoint at Week 16. Following the primary readout, placebo patients switched to sonelokimab, while those originally randomized to the active arm continued on the monthly 120mg maintenance dose. All patients have now completed Week 40, with a final assessment planned at Week 52.

Sonelokimab HS Results at Week 40

The Week 40 data, presented at AAD 2026 by MoonLake investigator Prof. Alexa Kimball of Harvard Medical School, showed consistent responses across both studies. In VELA-1, 61.9% of sonelokimab-treated patients achieved HiSCR75 and 32.4% achieved HiSCR100. In VELA-2, those figures were 61.8% and 28.1%, respectively. These are as-observed analyses, meaning they do not impute data for patients who discontinued.

Beyond the headline lesion counts, MoonLake reported that up to 77% of patients achieved an IHS4-55 response — a 55% or greater reduction in the International HS Severity Scoring System — and up to 25% reached what the company defined as inflammatory remission: complete resolution of abscesses, nodules, and draining tunnels simultaneously. Discontinuation rates were described as at the low end compared to other HS pivotal programs, though MoonLake did not disclose exact figures.

Patient-Reported Outcomes Tell a Parallel Story

The VELA clinical trial results also included a range of patient-reported outcome measures that tracked quality of life changes from baseline to Week 40. Mean HiSQOL scores — a validated HS-specific quality of life instrument — improved by 11.8 points in VELA-1 and 12.4 points in VELA-2 from baselines of 26.5 and 28.0, respectively. At baseline, 59% of patients fell into the "very severe" HiSQOL category; by Week 40, 63% had shifted to "mild or none."

Functional improvements were also recorded across individual HiSQOL-Mini items, with reductions ranging from 41% for pain to 54% for mobility-related tasks such as walking and getting dressed, and 62% for depressive symptoms. Up to 43% of patients with baseline worst skin pain scores of at least three points achieved a clinically meaningful three-point or greater reduction on the numerical rating scale. Separately, 65% of patients with baseline DLQI scores of four or higher achieved at least a four-point improvement — the threshold considered the minimal clinically important difference for that instrument.

Safety Profile Holds Steady

No new safety signals were detected through Week 40 in either VELA trial. The safety profile remained consistent with what had been observed in earlier studies of sonelokimab, including the Phase II MIRA trial in HS and the Phase IIb psoriasis study. MoonLake did not disclose specific adverse event rates or breakdowns in the press release.

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Where Sonelokimab Fits in the Hidradenitis Suppurativa Treatment Landscape

Sonelokimab is a tri-specific Nanobody that inhibits both IL-17A and IL-17F by blocking the IL-17A/A, IL-17A/F, and IL-17F/F dimers. A third domain binds human serum albumin, which the company says facilitates enrichment at sites of inflammatory edema. At approximately 40 kDa, it is substantially smaller than conventional monoclonal antibodies, a property that Nanobody-based therapeutics are designed to exploit for tissue penetration.

The IL-17 pathway has become a central therapeutic target in HS. Secukinumab (an IL-17A inhibitor) and bimekizumab (which targets both IL-17A and IL-17F) have both reached the market for moderate-to-severe HS. MoonLake itself drew a comparison in its press release, noting that approved IL-17A inhibitors have reported HiSCR75 rates of approximately 40% at one year, while approved IL-17A and IL-17F inhibitors have reported rates of approximately 60% at the same timepoint, based on pooled analyses of pivotal trials at approved doses.

The 62% HiSCR75 rate for sonelokimab at Week 40 — with Week 52 data still to come — places it in a range comparable to the dual IL-17A/F inhibitor class. Cross-trial comparisons are limited by differences in patient populations, trial design, endpoint timing, and statistical handling of intercurrent events, so direct conclusions about relative efficacy cannot be drawn from these figures alone. It is also worth noting that the VELA-2 trial narrowly missed statistical significance on its primary endpoint at Week 16 using the composite strategy (delta to placebo of 9%, p=0.053), though the combined VELA program met all primary and key secondary endpoints.

The HiSCR100 and inflammatory remission data — up to 32% and 25%, respectively — are less easily benchmarked against competitors, as these thresholds have not been uniformly reported across HS pivotal programs. If confirmed at Week 52, these higher-bar response rates could become a differentiating element in MoonLake's regulatory and commercial positioning.

MoonLake Immunotherapeutics Phase 3 Program: What Comes Next

MoonLake has outlined several near-term milestones. Week 52 data from VELA-1 and VELA-2 are expected in Q2 2026, which will provide the full dataset likely to support the company's planned BLA submission for HS in the second half of 2026. The company is also running the VELA-TEEN trial, an open-label Phase III study in adolescents aged 12–17 with moderate-to-severe HS — the first trial of its kind in this younger population.

Beyond HS, MoonLake's pipeline includes the Phase III IZAR-1 and IZAR-2 trials in psoriatic arthritis, with primary endpoint readouts expected in mid and late 2026, respectively. The AAD 2026 MoonLake presentation adds to a body of data that will be scrutinized closely as the company moves toward its first regulatory filing.


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