More than 80% of patients with axillary hyperhidrosis had clinically meaningful improvement with a novel topical anticholinergic treatment, a prospective clinical trial showed.
After 48 weeks of treatment, 86% of patients randomized to either of two concentrations of topical sofpironium bromide had at least a one-point improvement on the Hyperhidrosis Disease Severity Measure-Axillary (HDSM-Ax) scale. And 61-69% had at least a two-point improvement. Improvement occurred early and was evident within 2 weeks in 20-30% of patients.
Adverse events (AEs) were mostly mild and transient, decreasing over time with increased exposure to the medication, reported Stacy Smith, MD, of the California Dermatology and Clinical Research Institute in Encinitas, at the American Academy of Dermatology virtual meeting.
“From a patient-reporting perspective, the medication seems to work very well,” he said. “Looking at it over time, you can see that, just like the adverse events are better tolerated over time, the efficacy improves over time. Overall, we can say that patients tolerate it fairly well at the beginning, tolerate it better as time goes on, and continue to get increased improvement with respect to their measurement or their assessment of the hyperhidrosis.”
Sofpironium bromide is an analog of glycopyrrolate, which probably is the most widely used anticholinergic for primary axillary hyperhidrosis, Smith noted. In contrast to glycopyrrolate, sofpironium bromide is a retrometabolic molecule designed to be hydrolyzed into a less active ester. Glycopyrrolate does not undergo substantial metabolic breakdown before urinary excretion and has significant potential for systemic effects, he continued. Sofpironium bromide is rapidly metabolized into less active moieties. Its activity occurs primarily at the site of application and has fewer systemic effects.
Three different concentrations of sofpironium bromide gel were evaluated in a phase II randomized trial involving 227 adults with primary axillary hyperhidrosis. After 6 weeks of treatment, 70-79% of study participants had clinically meaningful improvement in hyperhidrosis, as defined by at least a one-point improvement in the HDSM-Ax.
Smith reported findings from a phase III trial to evaluate the long-term safety, tolerability, and efficacy of sofpironium bromide in patients ages ≥9 years with primary axillary hyperhidrosis. They were randomized 1:2 to 5% or 15% sofpironium gel, continued treatment for 48 weeks, and had an additional 4 weeks of follow-up.
“Importantly, this was not a rollover study,” he said. “In long-term safety studies, it’s very common to do the pivotal study, then do the long-term follow-up afterwards, so the patients are used to the medication. Brickell [the sponsor] did this differently so that they would get the information sooner, but that meant the patients who enrolled in the study were naive to the medication. Therefore, adverse events and so forth occurred early on, before patients were really used to the medication.”
Investigators enrolled 299 patients, 190 of whom completed the long-term open-label trial, 72 of 103 (70.6%) in the 5% arm and 118 of 197 (60%) in the 15% group. Most discontinuations (73) resulted from factors unrelated to AEs.
“As an investigator who does a lot of long-term safety studies, I can tell you that this level of participation over the long term is not unreasonable at all,” said Smith. “Most importantly, discontinuations due to adverse events is actually pretty low.”
Treatment-related adverse events (TRAEs) occurred substantially more often in the patients allocated to the 15% gel, 50.8% vs 22.5%. The incidence of severe TRAEs was 6.1% with 15% sofpironium bromide and 1.0%, and serious AEs occurred in 2.0% and 1.0% of the 15% and 5% arms. The frequency of treatment-emergent AEs decreased over time, from about 6% and 14% in the lower- and higher-dose groups at week 2 to about 2% and 3-4% at week 12.
Anticholinergic AEs occurred in 15.7% and 28.4% of the lower- and higher-dose groups. The most common anticholinergic effects were blurred vision (4.9% vs 18.8%), dry mouth (7.8% vs 16.8%), and mydriasis (1% vs 5.1%). Anticholinergic AEs led to discontinuation for 3% of the 5% group and 8.1% of the 15% arm.
At the end of treatment, 86.1% of patients randomized to 5% sofpironium bromide had at least a one-point improvement in the HDSM-Ax index, as did 85.8% in the 15% arm. The proportion of patients with at least a two-point improvement were 69.4% of the 5% group and 61.9% of the 15% group. About 60% of patients in each arm had two-point responses at 24-28 weeks, and the improvement was maintained to the end of the treatment period, said Smith.
Drug developer Brickell Biotech has chosen to seek FDA approval of the 15% gel, he added. The 5% solution has approval for axillary hyperhidrosis in Japan.
The study was supported by Brickell Biotech. Some co-authors are company employees.
Smith and co-authors disclosed relevant relationships with Brickell Biotech.