Adolescent HS Nod: First Biologic in Decade, Payer Proof Still Missing

CHMP Recommends Cosentyx for Adolescent Hidradenitis Suppurativa

Novartis announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending marketing authorization for Cosentyx (secukinumab) in adolescents aged 12 years and older with active moderate to severe hidradenitis suppurativa (HS) who have had an inadequate response to conventional systemic HS therapy. If approved by the European Commission (EC), Cosentyx would become the only interleukin-17A (IL-17A) inhibitor and the first innovative biologic treatment option for this population in Europe in nearly a decade, addressing a significant unmet medical need.

• The positive CHMP opinion positions Cosentyx to become the sole IL-17A inhibitor and the first innovative biologic treatment in almost ten years for adolescents aged 12 and older with moderate to severe HS in Europe, if approved by the European Commission. This addresses a critical gap in treatment options for a population where the disease often begins and can lead to irreversible scarring.
• The CHMP's recommendation is supported by evidence demonstrating that weight-based dosing of Cosentyx in adolescents achieves drug exposure comparable to that seen in adults with HS. This evidence integrates efficacy and safety data from adult HS clinical studies, pharmacokinetic modeling, and pediatric clinical trial data from other approved Cosentyx indications.
• Hidradenitis suppurativa is a chronic, progressive, and often painful inflammatory skin disease characterized by recurring abscesses and scarring, with over 50% of cases initiating during puberty. The disease significantly impacts quality of life, and the current treatment landscape for adolescents is notably limited, underscoring the importance of new therapeutic options.

Addressing the Critical Unmet Need in Adolescent HS

Recent literature from 2023 to 2026 highlights persistent unmet needs in hidradenitis suppurativa centered on refractory disease, pediatric onset, high-burden phenotypes, and underserved populations. Management remains challenging due to variable benefits of current therapies, diagnostic delay, and disparities in access to specialized dermatologic care and advanced treatments such as biologics.

• Pediatric and adolescent patients lacking standardized treatment guidelines: Current research highlights the lack of standardized pediatric guidelines for treatment of HS largely due to the varied nature of the disease and limited efficacy of current therapies, with treatment primarily relying on the management of HS in adults. Pediatric HS was associated with depression, anxiety, social withdrawal, shame, low self-esteem, and reduced quality of life, with emphasis on early diagnosis, routine screening, multidisciplinary management, and disparity-focused interventions.

• Severe, refractory and multi-failure patients after systemic antibiotics and biologics: Management of severe, refractory HS remains challenging, particularly in patients with inadequate response to systemic antibiotics and biologic therapies, including adalimumab therapy for six years with subsequent secondary failure, and secukinumab, which was discontinued because of clinical worsening. Published HS-specific reports remain limited to case reports of dual biologic or biologic plus Janus kinase inhibitor therapy, and studies of guselkumab in 10 adult patients with moderate-to-severe HS who had previously failed or were contraindicated for anti-TNFα and/or anti-IL-17 therapy.

• Patients with draining tunnels and high clinical and quality-of-life burden: Of 580 patients with moderate-severe HS, 46% had draining tunnels, with more abscesses, inflammatory nodules and scarring than those without. Patients with draining tunnels experienced significantly more inflammation/redness (73% vs. 63%), drainage from lesions (62% vs. 40%) and pain on sitting (48% vs. 37%), with significantly associated low mood/depression (30% vs. 18%), sleep disturbance (28% vs. 19%) and fatigue (28% vs. 18%), and often patients with tunnels who were eligible for biologics had not received them.

• Hispanic/Latino, Black or African American, and low socioeconomic status populations facing access disparities: In South Florida, HS disproportionately affects AA and Hispanic/Latino women, with almost half identifying as Hispanic or Latino (47.0%), and 31.7% identifying as Black or African American. Medicaid patients had higher rates of comorbid conditions, including cellulitis and psychiatric disorders, greater reliance on emergency departments, and higher utilization of prescription pain medications, particularly opioids, and were less likely to access specialized dermatologic care or advanced treatments such as biologics.

• Patients with obesity and metabolic dysregulation: HS is linked to systemic metabolic dysfunction, including components of metabolic syndrome such as obesity, hypertension, and hyperlipidemia, with HS visits having significantly higher odds of hypertension (adjusted odds ratio [aOR] 2.90), obesity (aOR 3.12), and hyperlipidemia (aOR 1.76). Current therapies yield variable benefits and do not target metabolic drivers, supporting investigation of tirzepatide, a dual GLP-1/GIP receptor agonist, and evaluation of bariatric surgery, which exhibited a significantly reduced risk of developing de novo HS (RR = .736 [.639; .847]).

Cosentyx's Established Safety Profile Supports Adolescent Use

Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, has demonstrated a favorable and consistent safety profile across moderate to severe plaque psoriasis, psoriatic arthritis and ankylosing spondylitis. In a pooled analysis of 10 phase II/III psoriasis studies including 3993 subjects with 3430 receiving secukinumab representing 2725 subject-years of exposure, over 52 weeks exposure-adjusted incidence rates per 100 subject-years for secukinumab 300 mg, 150 mg, and etanercept, respectively, were comparable for total adverse events (236.1, 239.9, and 243.4), infections (91.1, 85.3, and 93.7), serious adverse events (7.4, 6.8, and 7.0), serious infections (1.4, 1.1, and 1.4), malignant or unspecified tumors (0.77, 0.97, and 0.68), and adjudicated major adverse cardiovascular events (0.42, 0.35, and 0.34), with no meaningful difference between the 300- and 150-mg doses and, in terms of safety, comparable to etanercept. Longer-term integrated data from 21 randomized controlled trials in 5181, 1380, and 794 patients from psoriasis, psoriatic arthritis, and ankylosing spondylitis trials representing 10,416.9, 3866.9, and 1943.1 patient-years, respectively, plus post-marketing data with cumulative exposure of ~96,054 patient-years, and an update from 28 trials in 12,637 secukinumab-treated patients corresponding to 15,063, 5,985 and 3,527 patient-years of exposure in psoriasis, psoriatic arthritis and ankylosing spondylitis patients, showed low incidences of serious adverse events with no identifiable patterns across indications, with no apparent increases over time and no new safety signals identified for up to 5 years of treatment.

Across indications the most frequent adverse event was upper respiratory tract infection, with nasopharyngitis also frequently reported. Exposure-adjusted incidence rates per 100 patient-years across psoriasis, psoriatic arthritis, and ankylosing spondylitis indications were generally low for serious infections (1.4, 1.9, and 1.2, respectively), Candida infections (2.2, 1.5, and 0.7, respectively), and major adverse cardiac events (0.3, 0.4, and 0.6, respectively), while in the 28-trial update the incidence of opportunistic infections was <0.2/100 patient-years, the incidence of malignancy was ≤1/100 patient-years, and the incidence of major adverse cardiovascular events was <0.7/100 patient-years. Adverse events were not dose-related except for nonserious, mild/moderate, skin/mucosal candidiasis with incidence rates of 3.55, 1.85, and 1.37 for secukinumab 300 mg, 150 mg, and etanercept, respectively. No cases of tuberculosis reactivation were reported in the integrated dataset, active tuberculosis or latent tuberculosis infections were rare, and in a Brazilian real-world study of 152 patients with mean follow-up of 40.1 months no tuberculosis disease cases were recorded. The incidence of treatment-emergent anti-drug antibodies was low with no discernible loss of efficacy, unexpected alterations in pharmacokinetics, or association with immunogenicity-related adverse events. In psoriatic arthritis, 5-year FUTURE 1 results showed exposure-adjusted incidence rates per 100 patient-years for any secukinumab dose of serious infections (1.8), Crohn's disease (0.2), Candida infection (0.9), and major adverse cardiac events (0.5), with 81.8% (193 of 236) of patients in the secukinumab 150-mg group completing 5 years, and 4-year MEASURE 1 ankylosing spondylitis results showed rates of serious infections (1.0), Candida infections (0.4), Crohn's disease (0.6), ulcerative colitis (0.2), and malignant/unspecified tumours (0.5). In pediatric plaque psoriasis, pooled safety from two phase 3 trials in 198 pediatric patients (184.6 patient-years) alongside 1989 adult patients (1749.5 patient-years) showed exposure-adjusted incidence rates for treatment-emergent adverse events lower in the secukinumab-treated pediatric pool (198.8/100 PY) compared with etanercept (266.3/100 PY) and adult pools (256.1/100 PY), with rates of 167.7/100 PY and 214.7/100 PY in the 6 to <12 years and 12 to <18 years subgroups and 177.3/100 PY, 192.5/100 PY, and 206.8/100 PY in the <25 kg, 25 kg to <50 kg, and ≥50 kg subgroups, nasopharyngitis as the most frequently reported adverse event, one nail Candida, one skin Candida, and two vulvovaginal Candida events, transient and mostly mild neutropenia none leading to discontinuation, and no treatment-emergent anti-drug antibodies.

Inflammatory bowel disease events including Crohn's disease, ulcerative colitis and inflammatory bowel disease unclassified were uncommon and did not increase over time. In a retrospective pooled analysis of 21 trials in 7355 patients with cumulative exposure of 16,226.9 patient-years, among 5181 patients with psoriasis there were 14 cases of ulcerative colitis, 5 cases of Crohn's disease and 1 case of inflammatory bowel disease unclassified, with exposure adjusted incidence rates of 0.13, 0.05 and 0.01, respectively, of which 14 were new-onset; in 1380 patients with psoriatic arthritis there were 3 cases of ulcerative colitis, 3 cases of Crohn's disease and 2 cases of inflammatory bowel disease unclassified (exposure adjusted incidence rates 0.08, 0.08 and 0.05), with 7 new-onset cases; and among 794 patients with ankylosing spondylitis there were 4 cases of ulcerative colitis, 8 cases of Crohn's disease and 1 case of inflammatory bowel disease unclassified (exposure adjusted incidence rates 0.2, 0.4 and 0.1), with 9 new-onset cases. Rare cases of new-onset or exacerbation, including severe ulcerative colitis flare, asymptomatic Crohn's disease identified on screening colonoscopy, lymphocytic colitis, and paradoxical gastrointestinal effects that prevented approval in inflammatory bowel diseases, have been reported in case reports, case series and reviews, with literature noting that inflammatory bowel disease is more common in patients with psoriasis and that no causal relationship has been established.

Pioneering IL-17A Inhibition for Adolescent HS

The treatment landscape for moderate-to-severe hidradenitis suppurativa (HS) has expanded from single-agent tumor necrosis factor-alpha (TNF-α) blockade to include interleukin-17 (IL-17)-targeted biologics. Currently, only three biologic agents — adalimumab, secukinumab, and bimekizumab — hold regulatory approval for moderate-to-severe HS. Weekly adalimumab improved week-12 HiSCR in the phase 3 PIONEER trials; secukinumab, a selective IL-17A inhibitor, improved week-16 and week-52 outcomes in SUNSHINE/SUNRISE; and bimekizumab, a monoclonal antibody that selectively inhibits interleukin-17A and interleukin-17F, improved week-16 HiSCR50 in BE HEARD I/II. In a phase 2, double-blind, placebo-controlled randomized clinical trial, bimekizumab demonstrated a higher HiSCR rate vs placebo at week 12 (57.3% vs 26.1%; posterior probability of superiority equaled 0.998), with 46% achieving HiSCR75 and 32% achieving HiSCR90, whereas 10% of placebo-treated participants achieved HiSCR75 and none achieved HiSCR90.

Oral Janus kinase (JAK) inhibition has emerged as the most advanced small-molecule strategy, with oral JAK1 inhibition representing the most advanced small-molecule strategy for HS treatment. In a phase 2, randomized, double-blind, dose-ranging, placebo-controlled study of povorcitinib (selective oral Janus kinase 1 inhibitor) in 209 patients randomized 1:1:1:1 to povorcitinib 15, 45, or 75 mg or placebo for 16 weeks, povorcitinib significantly reduced abscess and inflammatory nodule count from baseline (least squares mean [SE] change: 15 mg, -5.2 [0.9], P = .0277; 45 mg, -6.9 [0.9], P = .0006; 75 mg, -6.3 [0.9], P = .0021) versus placebo (-2.5 [0.9]). STOP-HS1/STOP-HS2 enrolled 608/619 patients, respectively, and both povorcitinib doses met the primary endpoint of HiSCR50 at week 12; in STOP-HS1, 82/204 (40%) in the 45-mg group and 82/202 (41%) in the 75-mg group versus 60/202 (30%) in placebo achieved HiSCR50 (OR (95% CI) 45 mg: 1.6 (1.1-2.5), P = 0.0240; 75 mg: 1.6 (1.1-2.4), P = 0.0214). In a phase 2 trial (NCT04430855) in which 47 patients received upadacitinib 30 mg once-daily and 21 received placebo, a greater proportion receiving upadacitinib achieved HiSCR50 at week 12 vs a prespecified historical placebo rate (38.3% vs 25.0%; 1-sided P = .018). In a phase 2a umbrella trial, HiSCR at week 16 occurred in 33.3% (16/48) receiving placebo and in 51.9% (27/52), 34.0% (16/47), and 37.0% (17/46) receiving brepocitinib 45 mg, zimlovisertib 400 mg, and ropsacitinib 400 mg, respectively.

Additional targeted mechanisms have been evaluated in randomized trials with heterogeneous results, supporting a rationale for dual targeted therapy and biomarker-guided selection. In a phase 2, double-blind, placebo-controlled randomized clinical trial in 153 participants with moderate to severe HS who experienced anti-TNF treatment failure, 19 (48.7%), 22 (59.5%), and 10 participants (27.0%) receiving lutikizumab, a dual-variable domain interleukin 1α/1β antagonist, 300 mg every week, 300 mg every other week, and 100 mg every other week, respectively, achieved HiSCR50 at week 16 compared with placebo (35.0%). In a randomized, double-blind, placebo-controlled proof-of-clinical-concept study (NCT04762277) in 52 patients, the percentage change from baseline in total abscess and inflammatory nodule count at Week 12 was similar between spesolimab and placebo arms: -4.1% (-31.7, 23.4). In the randomized phase IIb SHINE study in 177 patients, vilobelimab treatment did not achieve significant HiSCR compared to placebo, with an unexpectedly high HiSCR placebo response of 47.1%. A living systematic review and network meta-analysis of 25 trials with HiSCR-50 data, including 5767 total patients and 39 unique treatments, found significantly higher HiSCR-50 response rates vs placebo for sonelokimab 120 mg every 4 weeks, lutikizumab 300 mg every 2 weeks, adalimumab 40 mg once per week, bimekizumab 320 mg every 2 weeks and every 4 weeks, povorcitinib 15 mg once per day, and secukinumab 300 mg every 4 weeks and every 2 weeks, while a meta-analysis of anti-IL17 drugs showed higher HiSCR (OR, of 1.96 [1.79-2.15]) and increased adverse effects (OR: 1.21 [1.09-1.34]), particularly due to Candida infections (OR, 5.61 [2.66-11.83]).