Once-daily sofpironium 12.45% gel improves axillary hyperhidrosis and is well tolerated over 6 weeks.

Background

Primary axillary hyperhidrosis affects quality of life and is often inadequately controlled by existing options such as antiperspirants, oral/topical anticholinergics, botulinum toxin, and surgical or device-based approaches. Sofpironium is a retrometabolically designed topical anticholinergic intended to maximize local efficacy with rapid systemic metabolism to reduce side effects.

Patients

• Total pooled N: 701 (Sofpironium 12.45%: n=353; Vehicle: n=348)
• Age: ≥9 years (median 31 years; ~94% ≥17 years)
• Key inclusion: Primary axillary hyperhidrosis ≥6 months; HDSM-Ax-7 baseline score 3–4; gravimetric sweat production (GSP) ≥150 mg (both axillae combined) in 5 minutes
• Key exclusions: Recent hyperhidrosis therapies (eg, botulinum toxin within 9 months; iontophoresis/thermolysis/surgery/serotonergic agents/prescription topicals per protocol windows; OTC antiperspirant within 1 week)
• Baseline severity: Median total GSP (both axillae) 211 mg

Intervention

Sofpironium topical gel 12.45%, applied by patients to each axilla once nightly at bedtime for 6 weeks.

Control

Matching vehicle gel, applied once nightly for 6 weeks.

Outcome

• Co-primary endpoints:
  • Proportion with ≥2-point improvement from baseline to end of treatment on HDSM-Ax-7
  • Change in gravimetric sweat production (GSP) from baseline to end of treatment
• Secondary endpoints:
  • Proportion with ≥1-point HDSM-Ax-7 improvement
  • Composite responses: ≥1-point HDSM-Ax-7 improvement + ≥50% GSP reduction; and ≥2-point HDSM-Ax-7 improvement + ≥70% GSP reduction
  • Time course of responses across study visits
• Safety: Treatment-emergent adverse events (AEs), anticholinergic AEs, local tolerability

Study Design

• Pooled analysis of two multicenter, randomized, double-blind, vehicle-controlled phase 3 trials (Cardigan I and II) conducted in the United States
• 1:1 randomization, stratified by site; daily application for 6 weeks
• Assessments included standardized morning GSP testing and HDSM-Ax-7
• Intent-to-treat efficacy analyses with prespecified imputation

Level of Evidence

Level I (pooled randomized controlled trials).

Follow up period

• Treatment duration: 6 weeks
• Post-treatment follow-up: 2 weeks after end of treatment (total 8 weeks from start)

Results

Primary outcomes

• HDSM-Ax-7 ≥2-point improvement: Sofpironium was superior to vehicle at end of treatment (statistically significant across pooled analysis; benefit evident from Day 8 through Week 6; effect waned 2 weeks post-treatment).
• GSP reduction: Greater reduction with sofpironium versus vehicle at end of treatment (statistically significant; superiority from Day 8 through Week 6; difference not sustained 2 weeks post-treatment).

Secondary outcomes (with NNT where calculable)

• HDSM-Ax-7 ≥1-point improvement:
  • Sofpironium 84.6% (270/319) vs Vehicle 72.3% (235/325)
  • Absolute benefit: 12.3% → NNT: 9
• Composite: ≥1-point HDSM-Ax-7 improvement + ≥50% GSP reduction:
  • Sofpironium 62.8% (199/317) vs Vehicle 45.3% (146/322)
  • Absolute benefit: 17.5% → NNT: 6
• Composite: ≥2-point HDSM-Ax-7 improvement + ≥70% GSP reduction:
  • Sofpironium 38.2% (121/317) vs Vehicle 17.7% (57/322)
  • Absolute benefit: 20.5% → NNT: 5
• Subgroups: Superiority of sofpironium consistent across sex, age, race, and ethnicity.

Safety

• Treatment-related AEs: 32.3% sofpironium vs 5.2% vehicle; generally mild–moderate; median onset ~1 week
• Common events (sofpironium): Dry mouth 14.2%, blurred vision 7.9%, application-site pain 7.9%, mydriasis 6.5%, erythema 6.2%, dermatitis 5.9%, pruritus 4.5%, urinary retention 2.3%
• Severe treatment-related AEs: 2.5% (no treatment-related serious AEs)
• Discontinuation due to AEs: 4.0% on sofpironium
• No clinically notable lab or vital sign differences; AE risk not influenced by sex, age, race, or ethnicity

Limitations

• Short treatment (6 weeks) and follow-up (2 weeks post-treatment) in these trials; durability beyond cessation not assessed here
• Some efficacy endpoints (eg, exact proportions for the ≥2-point HDSM-Ax-7 primary) not numerically reported in the pooled summary
• Vehicle produced some improvement, possibly reflecting emollient effects and study-related factors

Funding

• Phase 3 studies supported by Brickell Biotech, Inc.
• Manuscript preparation supported by Botanix SB Inc; medical writing by Diane K. Murphy, MBA.

Citation

Pariser D, Glaser DA, Del Rosso J, Bhatia N, Hooper D, Nestor MS, Smith S, Schlessinger J, Hebert A, Walker PS. Sofpironium topical gel, 12.45%, for the treatment of axillary hyperhidrosis: Pooled efficacy and safety results from 2 phase 3 randomized, controlled, double-blind studies. Journal of the American Academy of Dermatology. 2025;93:82-88. doi:10.1016/j.jaad.2025.02.086. Published online March 5, 2025.