What's the latest update on the ongoing clinical trials related to Hidradenitis Suppurativa?

Overview of Hidradenitis SuppurativaDefinitionon and Symptoms
Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disorder that typically manifests after puberty. It is characterized by recurrent, painful inflammatory nodules, abscess formation, draining sinus tracts, and eventual scarring in intertriginous areas, such as the axillae, groin, and anogenital regions. HS is known for its profound physical and psychological burden. Patients often experience severe pain and discomfort, malodor from chronic drainage, and disfiguring scars that significantly impair quality of life. In addition to the localized cutaneous manifestations, there is mounting evidence of systemic inflammation associated with HS, which can predispose patients to metabolic syndrome, inflammatory bowel disease, and other comorbidities.

Current Treatment Options
The management of HS remains challenging due to its multifactorial etiology. Current treatment options include a combination of medical and surgical approaches. First-line therapies often consist of topical antiseptics and antibiotics, with systemic antibiotics employed to target potential bacterial colonization and biofilm formation in the sinus tracts. The only biologic agent approved by regulatory authorities (FDA and EMA) for moderate-to-severe HS is adalimumab, a monoclonal antibody targeting TNF-α; however, its efficacy is variable and many patients require adjunct or sequential surgical interventions. Other medical treatments that have been explored include hormonal therapies for selected patients, systemic retinoids, and emerging immunomodulatory therapies. Surgical approaches, ranging from localized deroofing and limited excision to wide resection, are essential components of comprehensive HS management, especially in patients with extensive or refractory disease.

Clinical Trials for Hidradenitis Suppurativa

Types of Clinical Trials
Clinical trials in HS have evolved markedly over the past several years. The research landscape includes various phase II and III randomized controlled trials (RCTs) focusing on both medical and procedural interventions. An important aspect of these trials is the measurement of efficacy using outcome measures such as the Hidradenitis Suppurativa Clinical Response (HiSCR), the International Hidradenitis Suppurativa Severity Score System (IHS4), and several patient-reported outcome measures like pain numerical rating scales and the Dermatology Life Quality Index (DLQI).
Some trials focus on head-to-head comparisons between existing treatments (for example, comparing different dosing regimens of adalimumab or the efficacy of biosimilars). Others aim to explore novel therapeutic targets using emerging agents such as anti-IL-17 therapies (secukinumab and bimekizumab), IL-1 inhibitors like bermekimab, and complement inhibitors as well as small molecules targeting Janus kinase (JAK) pathways. Additionally, there are studies evaluating the combined use of biologic therapies with surgical interventions to ascertain whether a multimodal approach can enhance overall disease control.

Key Players and Institutions
The clinical trial landscape for HS is both global and multi-institutional, involving leading academic centers, pharmaceutical companies, and specialized dermatology research groups. Major institutions involved include renowned academic hospitals and research centers in North America, Europe, and Asia. Key companies such as Novartis, AbbVie, InflaRx, and MoonLake Immunotherapeutics are actively engaged in developing and testing novel agents. Furthermore, the international collaboration facilitated by groups like the Hidradenitis Suppurativa Core Outcomes Set International Collaboration (HiSTORIC) has been instrumental in standardizing outcome measures and trial protocols, thereby ensuring the robustness and comparability of trial results across different regions.

Recent Developments and Findings

Notable Trial Outcomes
Recent clinical trials have provided promising data regarding the efficacy and safety of several novel interventions in HS. For instance, clinical trials investigating adalimumab have shown that a significant proportion of patients achieve HiSCR at 12 weeks, with response rates ranging from approximately 42% to 59% compared to placebo, thus reaffirming its role as the current standard despite its limitations.
Moreover, the BE HEARD I and BE HEARD II trials have reported promising results with bimekizumab—a dual inhibitor of IL-17A and IL-17F. In these studies, a significantly higher proportion of HS patients reached HiSCR50 compared to placebo, and deeper levels of clinical response (HiSCR75 and HiSCR90) were observed, indicating that targeting IL-17 may be an effective strategy in a subset of patients with HS.
In addition, trials evaluating the IL-1 inhibitor bermekimab in phase II studies have shown improvements in inflammatory lesions, although these studies noted methodological challenges such as high placebo response rates and interrater variability, underlining the need for refined outcome measures and trial designs.
A particularly novel advancement comes from the evaluation of HSP90 inhibitors. Data from a Phase 1/2 trial of MC2-32 (RGRN-305) reported rapid improvements in key efficacy endpoints, including reductions in abscesses and inflammatory nodules, as well as favorable safety profiles. These outcomes suggest that small-molecule inhibitors might offer a new therapeutic avenue for HS patients who do not sufficiently respond to biologic therapies.
Further, emerging data on JAK inhibitors such as upadacitinib and povorcitinib have been encouraging. A recent Phase 2, dose-ranging study of povorcitinib demonstrated a clinically significant reduction in the number of abscesses and inflammatory nodules, highlighting the potential benefits of oral therapies that target the JAK/STAT pathway.
Recent trials have also explored the impact of combining medical treatments with surgical interventions. A controlled trial comparing adalimumab monotherapy versus adalimumab in combination with surgery has shown that patients receiving combination therapy—where surgery is administered as an adjunct to biologic treatment—achieve superior clinical and patient-reported outcomes. This approach suggests that the integration of multimodal treatment strategies is beneficial in managing the complex clinical manifestations of HS.

Emerging Therapies
Several emerging therapies have recently entered the clinical trial stage:

1. Sonelokimab: A novel Nanobody® designed to selectively inhibit IL-17 has shown promising results. A global Phase 2 study (MIRA) is investigating its efficacy in HS, with HiSCR75 as the primary endpoint. This study builds on positive data observed in a Phase 2b trial in psoriasis, suggesting that sonelokimab may yield rapid and durable responses in HS as well.
2. Izokibep: This small protein therapeutic is engineered to inhibit IL-17A with high potency. Early results from Phase 2b/3 trials indicate that izokibep may lead to early improvements in disease manifestations such as the reduction in draining tunnels, which are typically challenging to treat. Early data from independent HS and psoriatic arthritis trials reinforce its potential to resolve difficult-to-treat tissue manifestations and improve overall quality of life.
3. Vilobelimab: InflaRx is actively pursuing the development of vilobelimab, a complement (C5a) inhibitor, for HS. The company plans to submit a Special Protocol Assessment (SPA) to the FDA for a global Phase III trial. The European Medicines Agency has already provided positive feedback, and details regarding trial design and endpoints are being developed. This approach shows promise as an alternative strategy given the complex immune pathways involved in HS.
4. JAK Inhibitors: In addition to povorcitinib and upadacitinib, other agents targeting the Janus kinase pathways are undergoing early-phase evaluation. These oral agents represent an attractive therapeutic option due to their ease of administration and potential to modulate multiple inflammatory cytokines involved in HS pathogenesis.
5. HSP90 Inhibitors: The MC2-32 trial is among the first to evaluate HSP90 inhibitors for HS. By targeting a chaperone protein involved in multiple inflammatory pathways, this small-molecule approach offers the prospect of broad immunomodulatory activity with an acceptable safety profile.

Collectively, these emerging therapies reflect a shift toward targeting specific inflammatory pathways beyond TNF-α, aiming to address the diverse and complex immunopathogenesis of HS.

Future Directions and Implications

Ongoing Research
The ongoing research in HS clinical trials is characterized by a diverse array of interventions aimed at addressing different aspects of the disease. With the current reliance on adalimumab as the sole approved biologic, there is significant focus on identifying alternate and complementary therapies that might offer improved efficacy and safety profiles. The latest trials are addressing key gaps:

- Phase III Trials and Confirmatory Studies: Companies like InflaRx and MoonLake Immunotherapeutics are advancing their programs into Phase III, guided by encouraging phase II results. For example, InflaRx’s planned Phase III trial for vilobelimab is a crucial step in demonstrating the drug’s efficacy and safety in a broader patient population, and this trial is targeted to be initiated by the end of 2024.
- Combination Therapy Studies: Recognizing that monotherapy often falls short of achieving complete clinical resolution in HS, future research is increasingly focusing on combination therapies. Trials integrating biologic agents with surgical intervention have demonstrated that such approaches not only improve clinical endpoints such as HiSCR but also enhance patient quality of life and long-term disease control. This strategy represents a paradigm shift in the treatment landscape of HS, emphasizing the importance of multimodal management.
- Biomarker and Outcome Measure Refinement: One of the challenges in HS clinical trials has been the variability in outcome measures and the high placebo response rates observed in some studies. Ongoing research efforts aim to validate and standardize instruments such as the IHS4, HiSQOL, and dynamic pain indices to ensure that clinical trials can robustly and reliably capture treatment benefits. This research is key to informing both regulatory decisions and routine clinical practice.
- Patient-Centric Research and Real-World Evidence: In addition to controlled trials, real-world studies such as the HARMONY study provide critical insights into how treatments perform in heterogeneous patient populations outside the highly selective trial environments. The collection of robust real-world data on interventions like adalimumab has paved the way for better understanding treatment response, adherence, and long-term outcomes, which are essential for tailoring future therapeutic strategies.

Impact on Treatment Landscape
The collective advances from these ongoing clinical trials are expected to have far-reaching implications for the treatment landscape of HS. First, the introduction of novel agents that target key pro-inflammatory cytokines—such as IL-17, IL-1, and complement factors—promises to expand the therapeutic arsenal beyond TNF-α inhibitors. This diversification of treatment options may allow clinicians to personalize therapy based on disease phenotype, stage, and patient comorbidities.
Furthermore, the incorporation of combination therapies involving both medical and surgical interventions recognizes the complexity of HS. By targeting both active inflammation and the architectural damage (e.g., sinus tracts) that perpetuates disease chronicity, these approaches aim to achieve not just temporary symptom relief but also sustained remission. This is expected to lead to a reduction in disease flares, lower overall health care resource utilization, and improved quality of life for patients.
In the long term, ongoing trials of emerging agents such as sonelokimab and izokibep may also contribute to the development of faster-acting treatments with a more favorable safety profile compared to current treatments. The evolution of novel oral therapies, particularly JAK inhibitors, may also improve patient convenience and adherence—factors that are critical for chronic diseases like HS.
At the regulatory and clinical practice levels, the standardization of outcome measures and the incorporation of patient-reported outcomes into clinical trials will facilitate more accurate comparisons between treatments. This will, in turn, help guide treatment selection and result in more evidence-based, individualized management plans for HS patients. In parallel, the increasing emphasis on real-world evidence obtained from observational studies ensures that clinical trial data are interpreted within the broader framework of everyday clinical practice, enhancing the external validity and applicability of the research findings.

Conclusion
In summary, the latest updates on ongoing clinical trials related to Hidradenitis Suppurativa indicate a dynamic and rapidly evolving research landscape. Current trials are expanding the treatment options beyond the single approved agent, adalimumab, with multiple novel therapies such as dual IL-17 inhibitors (bimekizumab), specific IL-17 targeting small proteins (izokibep), complement inhibitors (vilobelimab), and innovative small-molecule inhibitors including HSP90 inhibitors (MC2-32). These studies rely on rigorous endpoints such as HiSCR, IHS4, and comprehensive quality-of-life assessments to evaluate efficacy and safety. Moreover, the integration of surgical interventions with medical therapies represents a significant paradigm shift, aiming to address the multifaceted nature of the disease.

Ongoing Phase III trials and confirmatory studies, with anticipated initiation timelines as early as late 2024, underscore the commitment of pharmaceutical companies and academic institutions to bring more effective treatments to patients. Researchers are also placing a strong emphasis on optimizing outcome measures and ensuring that trial eligibility criteria reflect the diverse patient populations seen in real-world clinical settings. This holistic approach is essential for the advancement of HS management, as it fosters a more personalized and patient-centric treatment strategy that incorporates both high-level evidence from controlled trials and the invaluable insights gained from real-world evidence.

Thus, from multiple perspectives—including novel molecular targets, combination therapies, and improved study designs—the future direction of clinical trials in HS is poised to substantially transform the therapeutic landscape. These advancements promise not only to provide more treatment choices for patients but also to enhance overall disease management, leading to sustained improvement in quality of life and reduced morbidity associated with this debilitating condition. The ongoing research efforts and emerging trial updates offer a hopeful outlook by paving the way for more effective, multifaceted treatment regimens in HS, thereby meeting a critical unmet need in dermatology.