Phase 3 Trial Shows Sonelokimab Achieves Durable, Near-Complete Clearance in One-Third of Hidradenitis Suppurativa Patients

For millions of people living with hidradenitis suppurativa, the standard of care has long been defined by managed disappointment. The chronic, systemic skin condition causes painful, recurrent abscesses and tunneling wounds, often leading to severe scarring and profound psychological distress. Historically, treatments have struggled to do more than blunt the disease's sharpest edges, leaving patients to endure a cycle of flare-ups and invasive surgeries. However, newly released 52-week data from a massive Phase 3 clinical program suggests a fundamental shift in what is medically possible for these patients.

MoonLake Immunotherapeutics has unveiled the full one-year results from its VELA-1 and VELA-2 global registrational trials, which evaluated the investigational drug sonelokimab in adults with moderate-to-severe hidradenitis suppurativa. The data, drawn from 838 participants across both identical trials, provides the most robust evidence to date that deep, durable disease clearance is achievable for a significant portion of the patient population. The findings are poised to support a Biologics License Application to the U.S. Food and Drug Administration by September 2026.[1][3]

The cornerstone of the evidence pack lies in the drug's ability to drive patients toward complete inflammatory remission. At the 52-week mark, 33.1 percent of patients treated with sonelokimab achieved HiSCR100, a stringent clinical endpoint indicating the total clearance of inflammatory lesions. This represents a remarkable departure from older therapeutic benchmarks, which typically celebrated a 50 percent reduction in symptoms as a clinical victory.[1][4]

Beyond total clearance, the broader efficacy metrics underscore the drug's sweeping impact. Across the pooled Phase 3 program, 67.2 percent of treated patients reached HiSCR75, meaning they experienced at least a 75 percent reduction in abscesses and inflammatory nodules without any worsening of draining tunnels. Furthermore, 26 percent of participants achieved an IHS4-100 response, a comprehensive measure of inflammatory remission that confirms the complete elimination of all active disease markers.[1][2]

To understand why sonelokimab is yielding these unprecedented response rates, researchers point to its unique molecular architecture. Unlike traditional monoclonal antibodies, sonelokimab is a nanobody—a fraction of the size of standard biologic drugs. This compact structure allows it to penetrate deeply into the dense, inflamed tissue characteristic of hidradenitis suppurativa lesions, reaching targets that larger molecules often struggle to access.[2][6]

The nanobody is engineered to be trivalent, meaning it has three distinct binding domains. Two of these domains selectively bind to and neutralize interleukins 17A and 17F, which are primary drivers of the runaway inflammatory cascade in hidradenitis suppurativa. By blocking both cytokines simultaneously, the drug effectively cuts off the biological signaling that causes the painful nodules to form.[1][6]

The third binding domain is perhaps the most critical innovation: it binds to human albumin. Because albumin naturally accumulates at sites of inflammatory edema, this domain essentially uses the body's own swelling response to ferry the drug directly to the deepest, most active lesions. This targeted enrichment mechanism explains both the rapid onset of action seen in earlier trial phases and the deepening of the clinical response over the full 52-week period.[1][6]

While the physical clearance of lesions is the primary clinical endpoint, the VELA trials also captured extensive data on the lived experience of the patients. Hidradenitis suppurativa is widely considered one of the most painful and debilitating of all dermatological conditions, often forcing patients to miss work, avoid social interactions, and suffer from secondary depression. The 52-week data revealed that patients receiving sonelokimab experienced an average 15-point improvement on the Hidradenitis Suppurativa Quality of Life scale.[1][4]

This numerical improvement translates to a profound shift in daily functioning. According to the trial investigators, the average patient moved from a state of "severe" impairment to "mild" impairment. Additionally, nearly half of the treated cohort reported a clinically meaningful reduction in skin pain, defined as at least a three-point drop on the standard numerical rating scale. For a disease where chronic pain is the most frequent complaint, this metric is arguably as important as the visual clearance of the skin.[1][2]

The evidence pack also includes highly anticipated interim data from the VELA-TEEN trial, which is evaluating sonelokimab in adolescents aged 12 to 17. Hidradenitis suppurativa often begins during puberty, and early intervention is considered crucial to preventing the irreversible tissue damage and tunneling that characterize the advanced stages of the disease. The 24-week adolescent data proved even more striking than the adult results.[1][4]

In the VELA-TEEN cohort, nearly 45 percent of adolescent patients achieved complete clearance (HiSCR100) by week 24, and approximately 68 percent reached the HiSCR75 threshold. These accelerated response rates suggest that intervening before the disease has caused decades of chronic inflammation and structural skin changes may yield vastly superior outcomes. The adolescent data will be included in the upcoming regulatory submission, potentially allowing for a broader initial label.[1][4]

Despite the overwhelmingly positive efficacy signals, the evidence pack does contain areas of transparent uncertainty that will require further observation. First, while the 52-week safety profile remained consistent with earlier readouts—showing no new safety signals or elevated rates of severe opportunistic infections—immunomodulatory drugs inherently carry long-term risks. Suppressing the IL-17 pathway can increase susceptibility to certain fungal infections, and regulators will want to see multi-year extension data to confirm the drug's safety over a lifetime of use.[2][6]

Second, the VELA trials were placebo-controlled, meaning sonelokimab was not tested head-to-head against the current standards of care, such as adalimumab or secukinumab. While cross-trial comparisons are statistically fraught, analysts note that sonelokimab's 33 percent complete clearance rate appears substantially higher than the historical performance of competing agents at similar timepoints. However, without a direct comparative trial, the exact magnitude of its superiority remains an educated estimate rather than a proven fact.[5][6]

Another variable is the performance of patients who crossed over from the placebo group to the active drug at week 16. The data showed that these patients experienced a rapid catch-up effect, with their HiSCR75 rates jumping by 20 percentage points within just four weeks of starting sonelokimab. This rapid rescue effect is highly encouraging for clinicians, as it suggests the drug can quickly halt disease progression even after a period of unmitigated inflammation.[4]

As MoonLake prepares to submit its Biologics License Application, the dermatological community is bracing for a paradigm shift. For decades, the treatment goal for hidradenitis suppurativa was merely to make the disease tolerable. The VELA data provides compelling evidence that the goalposts have moved. With one-third of patients achieving complete clearance and nearly 70 percent seeing profound reductions in their disease burden, the era of managing expectations may finally be giving way to the era of demanding remission.[6]