VIENNA – An investigational topical cholinergic receptor antagonist known as DRM04 achieved its efficacy and safety endpoints for the treatment of primary axillary hyperhidrosis in the pivotal phase III ATMOS-1 and ATMOS-2 trials.
“We haven’t had any good new treatment options for patients with hyperhidrosis for a long time,” Dr. David M. Pariser said, in presenting the pivotal trial outcomes data at the annual congress of the European Academy of Dermatology and Venereology.
ATMOS-1 and ATMOS-2 were identically designed 4-week, double-blind studies involving 697 patients with excessive underarm sweating who were randomized 2:1 to once daily use of DRM04 3.75% wipes or a vehicle control. The patients averaged 33 years of age, although as Dr. Pariser noted, primary axillary hyperhidrosis often begins in adolescence and patients as young as age 9 were enrolled. The majority of participants were female. Roughly two-thirds of subjects were grade 3 on the 4-point Hyperhidrosis Disease Severity Scale. The rest were grade 4.
The coprimary endpoints in ATMOS-1 and ATMOS-2 were a 4-point or greater improvement on the Axillary Sweating Daily Diary (ASDD) between baseline and week 4, and the absolute change from baseline in axillary sweat production measured gravimetrically.
The ASDD is a new patient-reported outcome measure developed specifically for the ATMOS trials. At baseline, participants scored a mean of 7.2 points on the 0-10 scale. A 4-point or greater improvement was seen at week 4 in 52.8% of ATMOS-1 participants on DRM04, compared with 28.3% of controls. In ATMOS-2, the spread was 66.1% vs. 26.9%.
Mean baseline sweat production was roughly 175 mg/5 min per armpit, a prodigious rate given that 50 mg/5 min is considered excessive. In ATMOS-1, the rate dropped by an adjusted average of 96.2 mg/5 min per armpit with active therapy, compared with 90.6 mg/5 min in the control group. In ATMOS-2, the DRM04 users had a mean drop in sweat production of 110.3 mg/5 min, compared with a reduction of 92.2 mg/5 min in the control group. Both of these differences were statistically significant and clinically meaningful, Dr. Pariser said.
The secondary endpoint in the studies was change in the Dermatology Life Quality Index from baseline to week 4. The improvement in DRM04 users averaged 8.1 points in ATMOS-1 and 8.6 points in ATMOS-2, both significantly greater than the 4.3- and 5.0-point improvements in the control arms.
In ATMOS-1, 9.2% of patients in the DRM04 arm dropped out of the study, in many cases because of anticholinergic side effects, the most common of which included dry mouth, dry eyes, urinary hesitation or less frequently retention, and constipation. These were mostly mild to moderate in nature and were generally responsive to temporary treatment discontinuation, which the study protocol allowed. The dropout rate in the DRM04 arm of ATMOS-2 was 6.8%.
Seven percent of subjects in the DRM04 study arms experienced mydriasis, most often unilaterally. Dr. Pariser said this might be due to patients touching an eye while they still had DRM04 on their hands, a problem that can be readily addressed in the medication use instructions.
The dropout rates in the control groups were 2.6% and 5%.
More than 80% of ATMOS-1 and ATMOS-2 participants enrolled in ARIDO, the 48-week, open label, phase III extension study of DRM04. Dermira, which is developing DRM04, has announced it plans to file for marketing approval by the Food and Drug Administration in the second half of 2017.
Dr. Pariser reported serving as an investigator for and consultant to Dermira, Brickell Biotech, and TheraVida.