Zura Bio Abandons Hidradenitis After Placebo Tie as Cash Funds Sclerosis Pivot

STOP-HS1 and STOP-HS2 phase 3 trials — povorcitinib: Adults with moderate to severe HS were randomized 2:2:1:1 to once-daily povorcitinib 45 mg, povorcitinib 75 mg, or placebo with crossover at week 12 to povorcitinib 45 mg or 75 mg through week 54. In STOP-HS1, 82/204 (40%) in the povorcitinib 45-mg group and 82/202 (41%) in the 75-mg group versus 60/202 (30%) in the placebo group 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); corresponding values for STOP-HS2 were 88/208 (42%) and 88/208 (42%) versus 58/203 (29%; OR (95% CI) 45 mg: 1.8 (1.2-2.8), P = 0.0035; 75 mg: 1.9 (1.2-2.8); P = 0.0033). Through week 12, serious treatment-emergent adverse events (AEs) occurred in 1-2% of patients across povorcitinib doses and in 2-3% with placebo; through week 54, serious AEs occurred in 5%/6% of patients receiving 45-mg/75-mg povorcitinib, respectively. The most frequent AEs among patients treated with 45-mg/75-mg povorcitinib were acne (17%/20%), nasopharyngitis (10%/12%) and upper respiratory tract infection (11%/10%).

Phase 2, randomized, placebo-controlled study (NCT04430855) — upadacitinib 30 mg once-daily: Forty-seven patients received upadacitinib; 21 patients received placebo. At week 12, a significantly greater proportion of patients receiving upadacitinib achieved HiSCR50 vs a prespecified historical placebo rate (38.3% vs 25.0%; 1-sided P = .018). Comparison with the in-trial placebo group showed an adjusted difference of 14.7% (nominal P = .087).

Phase 2, double-blind, placebo-controlled randomized clinical trial (NCT03248531) — bimekizumab (640 mg at week 0, 320 mg every 2 weeks): Bimekizumab demonstrated a higher HiSCR rate vs placebo at week 12 (57.3% vs 26.1%; posterior probability of superiority equaled 0.998, calculated using bayesian analysis). At week 12, 46% of bimekizumab-treated participants achieved HiSCR75 and 32% achieved HiSCR90, whereas 10% of placebo-treated participants achieved HiSCR75 and none achieved HiSCR90. Serious adverse events occurred in 2 of 46 bimekizumab-treated participants (4%), 2 of 21 placebo-treated participants (10%), and 1 of 21 adalimumab-treated participants (5%).

Loss of efficacy and limited durability of adalimumab: The number of cases not responding to adalimumab has been progressively increasing, with lack of improvement and progression within ongoing therapy leading to repeated hospitalizations and additional intravenous antibiotics, zinc, colchicine, and pain relievers. In 135 adults initiating adalimumab as first biologic therapy, Hurley stage 3 remained independently associated with less favorable durability (adjusted odds ratio 0.37, 95% confidence interval 0.17-0.81), while higher body mass index, diabetes, and lower hemoglobin were associated with lower durability in univariable analyses.

Flares and Staphylococcus aureus carriage predict poor response: In 115 patients treated with adalimumab, 80.9% of patients developed flares, detecting 252 flares, with joint analysis showing positive correlation between flare recurrence and no response (P<0.001) and occurrence of a flare before week 12 carrying the highest risk of no response (P<0.001). Nasal carriage of S. aureus was associated with loss of response, with 10.3% versus 50% carriage in responders versus flare-up patients at 12 weeks (odds ratio 8.67; 95% CI 1.54-48.49; p = 0.014) and 10% versus 41.7% at week 48 (odds ratio 6.42; 95% CI 1.00-41.20; p = 0.05).

Surgical recurrence and complications vary by modality: Primary closure had the highest recurrence (38.0%) and complication rates (29.4%), wide excision (n = 1923) showed moderate recurrence (17.2%) and the highest cosmetic dissatisfaction, and laser-assisted surgery had the lowest complication rate (2.2%) and recurrence rate (5.7%). In meta-analysis, estimated average recurrences were wide excision, 13.0% (95% confidence interval [CI], 5.0-22.0%); local incision, 22.0% (95% CI, 10.0-37.0%); and deroofing, 27.0% (95% CI, 23.0-31.0%).

Antimicrobial resistance limits antibiotic strategies: Staphylococcus aureus showed a 76.9% resistance to penicillin and a 58.3% resistance to fusidic acid, Staphylococcus lugdunensis showed 57.1% resistance to levofloxacin and 53.3% resistance to penicillin, and anaerobes showed 62.5%, 61.5%, and 53.8% resistance to erythromycin, clindamycin, and penicillin, respectively. In a separate cohort, the highest resistance rates were observed to ampicillin (n = 11, 47.8%), clindamycin (n = 7, 30.4%), and penicillin G (n = 7, 30.4%).

Comorbidity burden and diagnostic delay impair outcomes: Obesity was modestly associated with dehiscence and readmission for flap reconstruction, debridement, and skin-grafting techniques, dehiscence, and delayed wound healing, while diabetes was associated with increased hospital readmissions for debridement and flap reconstruction. Mean diagnostic delay was 13.7 years, pain was rated the most bothersome symptom, and higher Hurley stage at visit (p = 0.001), female gender (p = 0.018), and higher BDI-21 score (p = 0.022) significantly affected total DLQI score.