All the primary and secondary efficacy endpoints were met in Boulder, Colo.-based Brickell Biotech Inc.’s pivotal phase III study of the anticholinergic sofpironium bromide in treating primary axillary hyperhidrosis, which involves excessive sweating in the armpits that interferes with daily life and work.

It was these just-released data that prompted Kaken Pharmaceutical Co. Ltd., of Tokyo, Brickell’s development partner in the study, on Jan. 10 to submit an NDA for approval of manufacturing and marketing in Japan of sofpironium bromide for treating primary axillary hyperhidrosis. Kaken has the exclusive development, manufacturing and marketing rights for sofpironium bromide in Japan and certain other Asian countries.

Brickell stock (NASDAQ:BBI) rode high in trading June 15, closing up 50% at $1.89 per share.

Primary hyperhidrosis involves excessive sweating in the palms of hands, soles of feet, the groin and under the breasts. Primary axillary hyperhidrosis is excessive sweating under the armpits. The disorder is rare and affects an estimated 1% to 3% of the U.S. population. About half of people with hyperhidrosis have the axillary form, and roughly one-third of those individuals, or 1.3 million Americans, find the condition interferes negatively with their daily lives. After topical antiperspirants, patients generally turn to treatments intended to block the activation of, destroy or remove sweat glands by injectable, systemic, surgical or other means.

The phase III, double-blind, vehicle-controlled study evaluating the safety and efficacy of topically applied sofpironium bromide gel randomized 281 Japanese patients with primary axillary hyperhidrosis to receive the gel or placebo for 42 days. All subjects had Hyperhidrosis Disease Severity Scale (HDSS) scores ≥ 3 and ≥ 50 mg/5 min gravimetric sweat production (GSP) in each axilla at baseline.

In the primary endpoint, the proportion of subjects whose HDSS improved to score of 1 or 2 at the end of treatment (EOT) and > 50% reduction in GSP at EOT was 53.9% (SB) vs. 36.4% (vehicle), with a resulting “p” value of 0.003.

The competition

In February, Eli Lilly and Co., of Indianapolis, acquired Dermira Inc., of Menlo Park, Calif., which brought Qbrexza (glycopyrronium), a medicated cloth for topical treatment of primary axillary hyperhidrosis into the Lilly fold. The $1.1 billion in cash deal also brought Lilly lebrikizumab, a monoclonal antibody designed to bind IL-13 that is in phase III testing in atopic dermatitis.

In 2004, the FDA approved Allergan Inc.’s Botox (onabotulinumtoxinA) to treat severe axillary hyperhidrosis. The injected protein helps block secretion of the chemical that regulates the sweat glands in humans.

In July 2019, Dermata Therapeutics Inc. released positive phase I data from its study of DMT-410 (DMT-310 and botulinum toxin) for treating primary axillary hyperhidrosis. Topical DMT-310, a Spongilla lacustris powder, is designed to create channels through the stratum corneum for biologics to enter the dermis. The primary endpoints were the percent of patients with greater than 50% reduction in gravimetrically measured sweat production from baseline; the percent of patients with gravimetric sweat production less than 50 mg; and the mean absolute change from baseline in gravimetrically measured sweat production. At day 29, 80% of patients achieved an overall decrease in gravimetric sweat production of greater than 50%, while 85% of patients achieved a gravimetric sweat production of less than 50 mg, and the mean absolute change in gravimetric sweat production was -114.64 mg.

An acquisition and development deals

Kaken has other development partners. In March, Hitgen Inc., of Chengdu, China, said Kaken licensed for development a number of novel small-molecule leads for an undisclosed target identified by the company. Under the terms, Hitgen will grant exclusive rights to Kaken for further development and commercialization, and be eligible for preclinical and clinical milestone payments from Kaken as the project progresses, in addition to an up-front license fee. It's the second time Kaken has licensed candidates from Hitgen, the company said.

In June 2017, Kaken began a collaboration with Numab Therapeutics AG, of Wädenswil, Switzerland, for a discovery project to identify a multispecific antibody for an inflammatory indication. Kaken was to obtain an option to conclude a license and co-development agreement after identification of lead candidate generated by Numab using its unique multispecific antibody technology platform. Kaken was to fully fund the research program. Further financial details are not disclosed.

Last August, the stockholders of Vical Inc., of San Diego, approved the proposals required to complete its merger with Brickell. Vical had weighed strategic alternatives since 2018’s phase II failure of VCL-HB01, its Vaxfectin-formulated plasmid DNA vaccine against herpes simplex virus type 2.

No Comments