BACKGROUND: Facial angiofibromas (FAs) are a major feature of tuberous sclerosis complex (TSC). Topical rapamycin can successfully treat FAs. A new stabilized cream formulation that protects rapamycin from oxidation has been developed in 0.5% and 1% concentrations. OBJECTIVES: To assess the efficacy and safety of a novel, stabilized topical rapamycin cream formulation. METHODS: This multicentre double-blind randomized placebo-controlled dose-response phase II/III study with a parallel design included participants aged 6-65 years with FAs of mild or moderate severity according to the Investigator's Global Assessment (IGA) scale. Participants were randomized to one of three treatment arms: topical rapamycin 0.5%, topical rapamycin 1% or placebo. Treatment was applied once daily for 26 weeks. Safety and efficacy measures were assessed at days 14, 56, 98, 140 and 182. The primary endpoint was the percentage of participants achieving IGA scores of 'clear' or 'almost clear' after 26 weeks of treatment. Secondary measures included Facial Angiofibroma Severity Index (FASI) and participant- and clinician-reported percentage-based improvement. Safety measures included the incidence of treatment-emergent adverse events and blood rapamycin concentration changes over time. RESULTS: Participants (n = 107) were randomized to receive either rapamycin 1% (n = 33), rapamycin 0.5% (n = 36) or placebo (n = 38). All treated participants were included in the final analysis. The percentage of participants with a two-grade IGA improvement was greater in the rapamycin 0.5% treatment group (11%) and rapamycin 1% group (9%) than in the placebo group (5%). However, this was not statistically significant [rapamycin 0.5%: odds ratio (OR) 1.71, 95% confidence interval (CI) 0.36-8.18 (P = 0.50); rapamycin 1%: OR 1.68, 95% CI 0.33-8.40 (P = 0.53)]. There was a statistically significant difference in the proportion of participants treated with rapamycin cream that achieved at least a one-grade improvement in IGA [rapamycin 0.5%: 56% (OR 4.73, 95% CI 1.59-14.10; P = 0.005); rapamycin 1%: 61% (OR 5.14, 95% CI 1.70-15.57; P = 0.004); placebo: 24%]. Skin adverse reactions were more common in patients following rapamycin application (64%) vs. placebo (29%). CONCLUSIONS: Both rapamycin cream formulations (0.5% and 1%) were well tolerated, and either strength could lead to clinical benefit in the treatment of FA.

AFT Pharmaceuticals Ltd Auckland New Zealand

Bethesda Children's Hospital Budapest Hungary

Clinic of Neurology and Psychiatry for Children and Youth Belgrade Serbia

Department of Dermatology National Taiwan University Hospital and National Taiwan University College of Medicine Taipei Taiwan

Department of Medical Genetics Medical School University of Pécs Pécs Hungary

Department of Paediatric Dermatology Faculty Hospital Brno Czech Republic

Department of Pediatric Neurology Faculty of Medicine Comenius University National Institute of Children's Diseases Bratislava Slovakia

Departments of Dermatology and Pediatrics Mayo Clinic and Mayo Clinic Children's Center MN USA

Dermatology Department Christchurch Hospital Christchurch New Zealand

Dermatology Department Clínica Universidad de Navarra Madrid Spain

Division of Dermatology Phoenix Children's Hospital Phoenix AZ USA

Faculty of Medicine University of Belgrade Belgrade Serbia

Faculty of Medicine University of Queensland St Lucia QLD Australia

Helen DeVos Children's Hospital Grand Rapids MI USA

Johns Hopkins All Children's Hospital St Petersburg FL USA

Neurosciences Unit Queensland Children's Hospital South Brisbane QLD Australia

University of Belgrade School of Medicine Department of Dermatovenereology University Clinical Center of Serbia Belgrade Serbia

University of California San Diego Health Sciences Department of Neurosciences San Diego CA USA

University of Virginia Charlottesville VA USA

Br J Dermatol. 2023 Oct 25;189(5):507-508. doi: 10.1093/bjd/ljad334. PubMed

Br J Dermatol. 2023 Oct 25;189(5):e89. doi: 10.1093/bjd/ljad353. PubMed

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