Topical Anticholinergic Reduces Underarm Hyperhidrosis

Miriam E. Tucker

March 09, 2016

WASHINGTON, DC — An investigational anticholinergic topical gel is safe and effective for the treatment of axillary hyperhidrosis, according to results from a phase 2b study.

Sofpironium bromide (BBI-4000, Brickell Biotech) is one of several topical products currently being investigated in clinical trials, said David Pariser, MD, professor of dermatology at the Eastern Virginia Medical School in Norfolk, who is founding president of the International Hyperhidrosis Society.

The product is a specially formulated "soft" topical anticholinergic designed to block sweat production, and its rapid metabolic deactivation and excretion reduces the adverse effects associated with anticholinergic agents, such as dry eye and dry mouth.

"BBI-4000 is quickly metabolized, so it may be less likely to cause these anticholinergic effects," Dr Pariser told Medscape Medical News. "We'll know for sure when we see the much larger phase 3 trial data, but phase 2 looks good, and the rates of those side effects are low."

"It really appears to be a very safe and effective means of controlling sweating," said session moderator Sandy Sharon Tsao, MD, from the Massachusetts General Hospital in Boston.

Hyperhidrosis can severely affect patients' lives. "It is so devastating for people. They have to wear black clothing, have to carry multiple shirts, and really are limited and feel constricted in education, jobs, and relationships," Dr Tsao pointed out.

Current treatments for axillary hyperhidrosis include antiperspirants, which aren't very effective, and more invasive therapies, such as onabotulinumtoxin A (Botox, Allergan) injections and the microwave-based MiraDry system (Miramar Labs), she explained.

BBI-4000 involves minimal discomfort and patients can apply it at home. "If it's just as effective, it will be a wonderful treatment option," Dr Tsao said.

Dr Pariser presented the study results during a late-breaker session here at the American Academy of Dermatology 74th Annual Meeting.

Efficacy With Few Anticholinergic Effects

In the multicenter, double-blind, randomized, vehicle-controlled, dose-ranging study, 189 patients with primary axillary hyperhidrosis were randomized to BBI-4000, in 5%, 10%, or 15% concentrations, applied at bedtime daily for 28 days or to vehicle gel.

At baseline, all patients had a Hyperhidrosis Disease Severity Scale (HDSS) score of 3 or 4, and produced at least 50 mg of sweat in each axilla over 5 minutes.

In an intent-to-treat analysis, an improvement of at least 2 points on the HDSS at day 29 was achieved by significantly more patients treated with BBI-4000 15% than with placebo (38.3% vs 12.2%; P < .01).

On the Hyperhidrosis Disease Severity Measure Axillary (HDSM-Ax), a reduction of at least 1 percentage point was achieved by more patients treated with BBI-4000 15% than with placebo (72.3% vs 43.9%; P = 0.01). The same was true for a reduction of at least 2 percentage points (44.7% vs 19.5%; P = 0.01).

On Dermatology Life Quality Index (DLQI) scale, where a higher score indicates greater impairment, the dose-related decrease was 8.1 points with BBI-4000 15%, 5.8 points with BBI-4000 10%, 5.8 points with BBI-4000 5%, and 5.2 points with placebo.

On the measure of gravimetrically assessed sweat reduction, there was a trend toward significance for the gel, compared with placebo (P > .05). However, when a reduction of at least 1 percentage point on the HDSM-Ax was combined with a reduction of at least 50% in sweat production by day 29, BBI-4000 15% was significantly better than placebo (48.9% vs 26.8%; P = .03).

Topical irritation was infrequent. Localized dermatitis occurred in 6.1% of BBI-4000 patients, pain occurred in 2.6%, and pruritus occurred in 1.6%, but these effects weren't dose-related. All were mild or moderate and resolved spontaneously.

The rate of anticholinergic effects was low, occurring in less than 9% of patients overall. Dry mouth occurred in 8.3% of the BBI-4000 15% group, blurred vision in 6.3%, dysuria in 4.2%, and constipation in 2.1%; none of these effects were seen in the placebo group.

Dry eye and dry lips were seen in 2.1% of the BBI-4000 10% patients, but did not affect any of the BBI-4000 15% or placebo patients.

Overall, 16 patients (11.2%) experienced treatment-related adverse effects, but only one, in the BBI-4000 15% group, dropped out because of them. "There were no unexpected anticholinergic effects and no other systemic adverse events of note," Dr Pariser reported.

"There were a few cases of anticholinergic effects, but they weren't so significant that people wouldn't be interested in using it," Dr Tsao explained.

More Common Than Psoriasis

About 3% to 4% of the general population is affected by hyperhidrosis, making it more common than psoriasis. But patients often don't seek help because they don't realize their sweating is excessive or, if they do, they don't realize that anything can be done about it, Dr Pariser told Medscape Medical News.

Although there is a genetic component, he pointed out, "it's not the kind of thing that is discussed over the family dinner table."

The lack of understanding that excessive sweating is a medical condition extends to payers. The MiraDry isn't covered, for example, and it costs around $3000 for the three required treatments. "Some insurance companies, and even some physicians, view it as cosmetic. I do not," said Dr Pariser. "I feel that this is a medical condition that affects quality of life for patients as much as anything else we do in dermatology."

Dr Pariser reports financial relationships with Abbott Laboratories, Amgen, Astellas Pharma US, Asubio Pharmaceuticals, Basliea Pharmaceutica, Bickel Biotechnology, Biofrontera AG, Celgene, Dermira, Dow Pharmaceutical Sciences, DUSA Pharmaceuticals, Eli Lilly and Company, Galderma Laboratories LP, Genentech, Graceway Pharmaceuticals, Intendis, Janssen-Ortho, Johnson & Johnson Consumer Products, LEO Pharma, Medicis Pharmaceutical Corporation, MelaSciences, Novartis Pharmaceuticals, Novo Nordisk A/S, Ortho Dermatologics, Peplin, Pfizer, Photocure ASA, Procter & Gamble Company, Stiefel, and Valeant Pharmaceuticals International. Dr Tsao has disclosed no relevant financial relationships.

American Academy of Dermatology (AAD) 74th Annual Meeting. Presented March 5, 2016.

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