MoonLake's IL-17 Drug Faces Setback in Phase 3 HS Trial, Stock Plummets

MoonLake Immunotherapeutics experienced a significant setback as its investigational interleukin-17 (IL-17) inhibitor, sonelokimab, missed the primary endpoint in one of two identical phase 3 studies for moderate to severe hidradenitis suppurativa (HS). The news sent the company's stock price into a tailspin, dropping 87% in premarket trading on Monday.

Mixed Results from VELA-1 and VELA-2 Studies

The company conducted two phase 3 studies, VELA-1 and VELA-2, evaluating a single 120-mg dose of sonelokimab in 838 patients with moderate to severe HS. The primary endpoint was the proportion of patients achieving at least a 75% reduction in abscess and inflammatory nodule count compared to placebo.

Results from the studies showed:

• VELA-1: 34.8% of patients achieved the primary endpoint
• VELA-2: 35.9% of patients achieved the primary endpoint

However, the placebo response rates differed significantly between the two studies:

• VELA-1: 17.5% placebo response rate
• VELA-2: 25.6% placebo response rate

The unexpectedly high placebo response in VELA-2 resulted in the study failing to meet its primary endpoint when analyzed individually. Despite this, MoonLake claims an overall win based on pre-specified analysis methods that allow for consideration of data "irrespective of intercurrent events."

Company Response and Future Plans

Dr. Kristian Reich, Chief Scientific Officer at MoonLake, expressed mixed feelings about the results:

"We are encouraged by the results of VELA-1, which follow the expected performance of sonelokimab in all the important metrics for patients and treating physicians. The higher-than-expected placebo response rate in VELA-2 is disappointing but we are encouraged by the consistent performance of sonelokimab arms across all endpoints in both studies."

MoonLake plans to discuss the unexpected placebo data with regulators while continuing to pursue potential approval for sonelokimab. The company has several ongoing studies, including:

• 52-week data from VELA-1 and VELA-2 expected in Q2 2026
• Phase 2 study in palmoplantar pustulosis with results due this year
• Phase 2 study in axial spondyloarthritis and phase 3 studies in adolescent HS and psoriatic arthritis, with results expected next year

Market Impact and Industry Implications

The mixed results have cast doubt on sonelokimab's potential, which had previously attracted attention from major pharmaceutical companies. In June, the Financial Times reported that Merck & Co. had submitted a non-binding offer valuing MoonLake at over $3 billion earlier this year, though the offer was rejected.

MoonLake licensed sonelokimab from Germany's Merck KGaA in 2021. The molecule was originally developed by nanobody specialist Ablynx, now part of Sanofi.

As the company navigates this setback, the broader implications for IL-17 inhibitors and the competitive landscape in inflammatory disease treatments remain to be seen. The pharmaceutical industry will be watching closely as MoonLake works to address the unexpected results and chart a path forward for sonelokimab.