Dr. August Wolff Submits Application for Marketing Authorization of 1% Glycopyrronium Bromide (GPB) Cream in the EU – Positive Phase 3a Part of Pivotal Study Results for 1% GPB Cream in Patients with Primary Axillary Hyperhidrosis

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  • Filing of the documents for marketing authorisation application (MAA) in a decentralised procedure (DCP) on February 26th, 2021
  • Primary endpoint (absolute change in sweat production) was met with statistical significance
  • Key seconday endpoints showed about 2 times as many responders to 1% GPB treatment than to placebo

The Bielefeld-based family-owned pharmaceutical developing and manufacturing company  Dr. August Wolff GmbH & Co. KG Arzneimittel (“Dr. August Wolff”) announces that the “Marketing Authorisation Application” (MAA) for 1% Glycopyrronium bromide (GPB) cream was submitted on February 26th to the Medical Products Agency (MPA, Sweden) despite the challenges of the COVID-19 pandemic. If approved, the MAA would apply to Austria, Croatia, Denmark, Estonia, Finland, Germany, Latvia, Lithuania, The Netherlands, Norway and Sweden. Dr. August Wolff will commercialize the GPB Cream directly or with experienced partners in these countries.

The application package for 1% GPB cream includes i.a. data from a combined Phase 3a/Phase 3b study in patients with primary axillary hyperhidrosis. The long-term part of the study will be completed beginning of Q4 2021. Positive results of the Phase 3a part of the pivotal Phase 3 study in patients with primary axillary hyperhidrosis were recently published in British Journal of Dermatology[1]. The primary endpoint (absolute change in sweat production assessed by gravimetric measurement from Baseline (Day 1) to Day 29 in the 1% GPB group compared with the placebo group was met with statistical significance. In addition, hyperhidrosis-related quality of life improved significantly. 

“We are extremely encouraged by these positive results which together with results from planned interim analyses of the Phase 3b part are used for the filing of the marketing authorization application  in EU” said Eduard R. Dörrenberg, one of the Dr Wolff´s Managing Partners. “Once approved, the cream will be the first topical GPB treatment for primary axillary hyperhidrosis in Europe. Given that many hyperhidrosis patients do not achieve satisfactory results with existing treatments, we believe that our product might contribute significantly to improve the outcomes for patients suffering from this disease.”

Detailed study results of the phase 3a part

The Phase 3a part of this pivotal Phase 3 study, conducted in Germany, Hungary, Poland, Sweden, Denmark and UK, evaluated a total of 171 subjects randomized 1:1 to apply 1% GPB (n=84) or vehicle cream (placebo, n=87) to the axillae for 28 days. All subjects had Hyperhidrosis Disease Severity Scale (HDSS) scores ≥ 3 and ≥ 50 mg/5 min gravimetric sweat production in each axilla at baseline. Overall favourable results for 1% GPB Cream over Placebo were shown as follows:

Mean sweat production was reduced by 197.08 mg for the 1% GPB cream and 83.49 mg for placebo. Absolute reduction in sweat production from Baseline to Day 29 in logarithmic values was statistically larger in the 1% GPB cream compared to placebo (p = 0.0038; mixed effects model). Hence, the primary endpoint of the study was met. HDSS showed a change from baseline clearly favoring 1% GPB treatment over placebo at day 15 (difference in median: -1.0; p = 0.0020) and day 29 (p = 0.0138). Response to treatment based on the HDSS (an improvement of 2 points or more), a key secondary endpoint (for day 29) nearly reached statistical significance (p = 0.0542).

For the HidroQoL© the median improvement in the total score, a key secondary endpoint, was significantly greater for 1% GPB cream (- 6.0 points) than for placebo (-1.0 point) (p < 0.0001) on day 29. Similar results were observed for the individual domains daily life activity and psychosocial life. The proportion of HidroQoL©-responders with 1% GPB cream (59.8%) compared to placebo (26.2%) (p < 0.0001) was significant as determined in a post-hoc analysis (MCID ≥4).

Overall, the proportion of patients achieving sweat reduction was approximately two-fold higher for the 1% GPB cream (-197.08 mg) than for placebo (-83.49 mg). Similar results were seen for HDSS (23% GPB vs 11.9% placebo) and HidroQoL© (59.8% GPB vs. 26.2% placebo). Treatment was safe, most TEAEs were mild or moderate and transient and did not lead to discontinuation of the study. Local tolerability was very good with 9.2% of patients having only mild or moderate application site reactions. The most reported ADR was dry mouth (16.1%), an expected anticholinergic effect of the treatment. Application site reactions were reported in 9.2% of patients in the 1% GPB group and 7.1% of patients receiving placebo and were primarily mild to moderate in severity.

About ongoing phase 3b part

Ongoing Phase 3b part is investigating the long-term safety and efficacy of 1% GPB cream up to 72 weeks.  Enrollment of the Phase 3b part has been completed. In total, 517 patients have been enrolled. For the MAA dossier, long-term safety data over 6 months are available for 315 patients, and 12-month data are available for 100 patients. The study is continuing treatment for 72 weeks, to collect further long-term safety data.

About Glycopyrronium bromide

Glycopyrronium bromide (INN name, abbreviation GPB) or glycopyrrolate (USAN name) is a well-known anticholinergic acting drug substance approved in several marketed products in the EU and the USA for various diseases of children and adults. GPB blocks the action of acetylcholine at cholinergic receptors responsible among others for sweat gland activation.

About Hyperhidrosis

Approximately 5% people worldwide suffer from permanent excessive sweating, so-called “primary hyperhidrosis” which is a great burden for the patients and has severe impact on the quality of life. Yet, more than 50% of all hyperhidrosis patients receive no treatment. Patients with primary axillary hyperhidrosis suffer from an excessive amount of sweat production in the armpits beyond what is needed in order to regulate normal body temperature. Primary hyperhidrosis can range in severity from mild dampness to severe dripping and can result in substantial impairment in quality of life. This may significantly affect work, social and romantic relationships, physical and leisure activities as well as emotional and mental health.

About Dr Wolff

Ever since its establishment in 1905, Dr. Wolff, together with leading scientist in the field, develops products that solve the skin, hair and dental problems. The focus of the company are products with scientifically proven benefits. From the first branded product Haematopan to the products available internationally today, Dr. Wolff´s innovative product development provides the basis for new active ingredients and product developments. The company is now in its fourth generation of family-run management and is on a worldwide growth course with 780 employees. Dr. Wolff operates in 62 countries. For further information please visit Dr. Wolff Group.

[1] Abels C, Soeberdt M, Kilic A, Reich H, Knie U, Jourdan C, Schramm K, Heimstaedt-Muskett S, Masur C, Szeimies RM. A 1% glycopyrronium bromide cream for the topical treatment of primary axillary hyperhidrosis: Efficacy and Safety Results from a Phase 3a Randomised Controlled Study. Br J Dermatol. 2021 Jan 14. doi: 10.1111/bjd.19810.