Data from glycopyrronium tosylate Phase 3 program and olumacostat glasaretil Phase 2 trial show patients experienced early and sustained clinical effects with each treatment
ORLANDO, Fla., March 03, 2017 (GLOBE NEWSWIRE) -- Dermira, Inc. (NASDAQ:DERM), a biopharmaceutical company dedicated to bringing biotech ingenuity to medical dermatology by delivering differentiated, new therapies to the millions of patients living with chronic skin conditions, today announced new data, from its glycopyrronium tosylate (formerly DRM04) and olumacostat glasaretil (formerly DRM01) clinical programs, were presented in separate poster sessions at the 75th Annual Meeting of the American Academy of Dermatology (AAD) in Orlando, Florida.
Glycopyrronium tosylate is formulated as a topical, once-daily anticholinergic agent that is currently in development for the treatment of primary axillary hyperhidrosis (excessive underarm sweating). Olumacostat glasaretil is a novel, small molecule designed to target sebum production following topical application, in development for the treatment of acne vulgaris.
Building on previously reported results from the glycopyrronium tosylate Phase 3 clinical program and the olumacostat glasaretil Phase 2b dose-ranging trial, new data presented today at AAD showed that patients who received treatment with these investigational topical therapies in the respective trials experienced early and sustained clinical effects compared to vehicle.
“Hyperhidrosis has historically been an undertreated and underserved skin condition. As a result, millions of patients have been suffering silently,” said David Pariser, M.D., professor at Eastern Virginia Medical School, Department of Dermatology. “These new time course data are exciting because treatment with glycopyrronium tosylate not only resulted in statistically significant improvements in sweating severity at four weeks, but patients began to see reductions in sweating severity after the first week of treatment.”
“Dermira is advancing clinical programs in primary axillary hyperhidrosis and acne vulgaris, both areas of great unmet need where the standard of care hasn’t changed significantly in several decades,” said Eugene A. Bauer, M.D., chief medical officer of Dermira and a dermatologist. “These new data demonstrate that patients applying glycopyrronium tosylate and olumacostat glasaretil topically began to experience reductions in sweating severity and acne lesions early in their treatment cycles.”
Glycopyrronium Tosylate Phase 3 Clinical Program in Primary Axillary Hyperhidrosis
- In June 2016, Dermira reported data from ATMOS-1 and ATMOS-2, two identical Phase 3 multi-center clinical trials that evaluated the efficacy and safety of glycopyrronium tosylate 3.75% compared to vehicle in adolescent and adult patients (ages nine and older) with primary axillary hyperhidrosis.
- In the ATMOS-1 trial, 229 patients were randomized to receive glycopyrronium tosylate and 115 patients were randomized to receive vehicle; and in the ATMOS-2 trial, 234 patients were randomized to receive glycopyrronium tosylate and 119 patients were randomized to receive vehicle. Patients were instructed to apply the study product to each underarm once daily for four weeks using topical wipes containing either glycopyrronium tosylate or vehicle only.
- The co-primary endpoints were the proportion of patients who achieved at least a four-point improvement from baseline in sweating severity as measured by the Axillary Sweating Daily Diary (ASDD), Dermira’s proprietary patient-reported outcome (PRO) instrument, and the average absolute change from baseline in gravimetrically-measured sweat production.
- In both trials, the effect of treatment with glycopyrronium tosylate compared to vehicle, as measured by both ASDD and reduction in sweat production, were observed at week 1, and continued through week 4 of the 4-week trial.
- Glycopyrronium tosylate-treated patients began to see an improvement in sweating severity compared to vehicle, as measured by ASDD, at week 1 in ATMOS-1 (22.9% vs. 5.3%) and ATMOS-2 (29.0% vs. 4.2%), that continued through the completion of the 4-week treatment period.
- Patients also began to experience a reduction in gravimetrically-measured sweat production compared to vehicle beginning at week 1 in ATMOS-1 (-75.5 mg vs. -58.0 mg) and ATMOS-2 (-108.0 mg vs. -56.8 mg).
Consistent with the results from the Phase 2 clinical program, glycopyrronium tosylate was generally well-tolerated with side effects that were primarily mild to moderate in severity. The most frequently reported adverse events across both trials compared to vehicle were dry mouth, application site pain, dilated pupil (mydriasis), headache, sore throat (oropharyngeal pain), upper respiratory tract infection, blurred vision, urinary hesitation and dry eye. There was one treatment-related serious adverse event reported in the ATMOS-1 trial for a patient treated with glycopyrronium tosylate who reported a dilated pupil. There were no treatment-related serious adverse events reported in the ATMOS-2 trial.
Dry mouth, dilated pupil, blurred vision, urinary hesitation and dry eye are well-known, reversible side effects of anticholinergic agents.
Olumacostat Glasaretil Phase 2b Dose-Ranging Study in Acne Vulgaris
- In May 2016, Dermira reported topline results from the Phase 2b dose-ranging study evaluating the efficacy and safety of olumacostat glasaretil in patients with facial acne vulgaris compared to vehicle.
- In the Phase 2b dose-ranging trial, 420 patients were randomized into five separate arms and instructed to apply olumacostat glasaretil at concentrations of 4.0% once daily (n=106), 7.5% once daily (n=110) or 7.5% twice daily (n=101), or to apply vehicle once or twice daily (n=53 and n=50, respectively), in all cases for 12 weeks.
- The primary endpoints were absolute changes from baseline in inflammatory and non-inflammatory lesion counts and the proportion of patients achieving at least a two-point improvement from baseline in the five-point Investigator’s Global Assessment (IGA) scale. Each endpoint was measured at the end of the 12-week treatment period.
- Olumacostat glasaretil demonstrated statistically significant improvements from baseline to week 12 relative to the combined vehicle group in all primary efficacy endpoints at the highest dose of olumacostat glasaretil tested and in most primary endpoints at the two lower doses tested.
- Patients in the trial began to experience a reduction in inflammatory lesions with olumacostat glasaretil compared to vehicle at week 4 (-9.2, -8.6, -8.7 for olumacostat glasaretil 7.5% twice daily, 7.5% once daily and 4.0% once daily, respectively, vs. -7.2 for vehicle), which continued through week 8 (-12.3, -12.8, -12.3 vs. -9.7) and through to the end of the 12-week treatment period (-15.0, -14.5, -14.6 vs. -10.7).
- Reductions in non-inflammatory lesions with olumacostat glasaretil compared to vehicle were seen at week 4 (-8.6, -7.7, -8.3 for olumacostat glasaretil 7.5% twice daily, 7.5% once daily and 4.0% once daily, respectively, vs. -6.8 for vehicle), which continued through week 8 (-12.5, -11.9, -13.3 vs. -8.7) and through to the end of the 12-week treatment period (-17.5, -13.4, -15.3 vs. -9.3).
Consistent with an earlier Phase 2a study, olumacostat glasaretil was well-tolerated. Adverse events were primarily mild or moderate in severity. The most frequently reported adverse events across all three treatment groups were the common cold (nasopharyngitis), upper respiratory tract infection and application site itching (pruritus). No treatment-related serious adverse events were reported.
Based on the results of the two Phase 2 trials, in December 2016 Dermira initiated a Phase 3 clinical program evaluating the safety and efficacy of olumacostat glasaretil in patients with facial acne vulgaris.
About Glycopyrronium Tosylate
Glycopyrronium tosylate is formulated as a topical, once-daily anticholinergic agent that is currently in clinical development for the treatment of primary axillary hyperhidrosis. Glycopyrronium tosylate is designed to block sweat production by inhibiting the interaction between acetylcholine and the cholinergic receptors responsible for sweat gland activation. Dermira intends to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for glycopyrronium tosylate for the treatment of primary axillary hyperhidrosis in the second half of 2017, subject to the completion of registration-enabling activities.
Hyperhidrosis is a condition of sweating beyond what is physiologically required to maintain normal thermal regulation. Sweat is produced by glands in the skin and released to the skin surface through ducts. Sweat gland activity is controlled by the nervous system. The nervous system transmits signals to the sweat glands through acetylcholine, which is a known neurotransmitter. Primary hyperhidrosis, which is excessive sweating without a known cause, can affect the underarms, palms of the hands, soles of the feet, face and other areas. Several studies have demonstrated that excessive sweating often impedes normal daily activities and can result in occupational, emotional, psychological, social and physical impairment. Studies also suggest that the negative impact caused by excessive sweating has been reported to be similar to, if not greater than, the negative impact caused by conditions, such as psoriasis and other chronic diseases. According to a survey published in 2016, the prevalence of hyperhidrosis in the United States is estimated to be 4.8% of the population, or approximately 15.3 million people. According to this published study, 65% of hyperhidrosis sufferers in the United States have axillary hyperhidrosis, and approximately half of those axillary hyperhidrosis sufferers, or 5.2 million Americans, have severe disease that is barely tolerable and frequently interferes or is intolerable and always interferes with daily activities.1
About Olumacostat Glasaretil
Olumacostat glasaretil is a novel, small molecule designed to target sebum production following topical application. Sebum is an oily substance made up of lipids produced by glands in the skin called sebaceous glands, and excessive sebum production is an important aspect of acne that is not addressed by available topical therapies. Olumacostat glasaretil is designed to exert its effect by inhibiting acetyl coenzyme-A carboxylase, an enzyme that plays an important role in the synthesis of fatty acids, a type of lipid that represents an essential component of the majority of sebum lipids. Olumacostat glasaretil is currently being evaluated in two Phase 3 trials, CLAREOS-1 and CLAREOS-2, assessing its safety and efficacy. An additional open-label trial, CLARITUDE, is evaluating the long-term safety of olumacostat glasaretil. Topline results from the CLAREOS-1 and CLAREOS-2 trials are expected in the first half of 2018.
According to the American Academy of Dermatology, acne is the most common skin condition in the United States, affecting approximately 50 million Americans and 85% of all teenagers. Acne is caused by the accumulation of dead skin cells, oil and bacteria in pores. It is characterized by clogging of the pores and associated local skin lesions. Acne lesions are believed to result from an interaction of multiple pathogenic, or contributing, factors, including excessive sebum production. Acne is not just about blemishes on the skin; it can also affect a person’s quality of life, resulting in social, psychological and emotional impairments.
- Doolittle et. al., Hyperhidrosis: an update on prevalence and severity in the United States. Arch. Dermatol Res 308:743-749, 2016.
Dermira is a biopharmaceutical company dedicated to bringing biotech ingenuity to medical dermatology by delivering differentiated, new therapies to the millions of patients living with chronic skin conditions. Dermira is committed to understanding the needs of both patients and physicians and using its insight to identify and develop leading-edge medical dermatology programs. Dermira’s product pipeline includes three Phase 3 product candidates that could have a profound impact on the lives of patients: glycopyrronium tosylate, in development for the treatment of primary axillary hyperhidrosis (excessive underarm sweating); CIMZIA® (certolizumab pegol), in development in collaboration with UCB Pharma S.A. for the treatment of moderate-to-severe chronic plaque psoriasis; and olumacostat glasaretil, in development for the treatment of acne vulgaris. Dermira is headquartered in Menlo Park, Calif. For more information, please visit www.dermira.com.
In addition to filings with the Securities and Exchange Commission (SEC), press releases, public conference calls and webcasts, Dermira uses its website (www.dermira.com) and LinkedIn page (https://www.linkedin.com/company/dermira-inc-) as channels of distribution of information about its company, product candidates, planned financial and other announcements, attendance at upcoming investor and industry conferences and other matters. Such information may be deemed material information and Dermira may use these channels to comply with its disclosure obligations under Regulation FD. Therefore, investors should monitor Dermira’s website and LinkedIn page in addition to following its SEC filings, press releases, public conference calls and webcasts.
The information in this press release contains forward-looking statements and information within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, which are subject to the “safe harbor” created by those sections. This press release contains forward-looking statements that involve substantial risks and uncertainties, including statements with respect to timing expectations for the receipt and announcement of topline results from, and the successful completion of, Dermira’s CLAREOS-1, CLAREOS-2 and CLARITUDE trials; and the timing and submission of an NDA to the FDA for glycopyrronium tosylate. These statements deal with future events and involve known and unknown risks, uncertainties and other factors that may cause actual results, performance or achievements to be materially different from the information expressed or implied by these forward-looking statements. Factors that could cause actual results to differ materially include risks and uncertainties such as those relating to the design, implementation and outcome of Dermira’s clinical trials; Dermira’s dependence on third-party clinical research organizations, manufacturers and suppliers; the outcomes of future meetings with regulatory agencies; Dermira’s ability to obtain regulatory approval for its product candidates; and Dermira’s ability to continue to stay in compliance with applicable laws and regulations. You should refer to the section entitled “Risk Factors” set forth in Dermira’s Annual Report on Form 10-K, Dermira’s Quarterly Reports on Form 10-Q and other filings Dermira makes with the SEC from time to time for a discussion of important factors that may cause actual results to differ materially from those expressed or implied by Dermira’s forward-looking statements. Furthermore, such forward-looking statements speak only as of the date of this press release. Dermira undertakes no obligation to publicly update any forward-looking statements or reasons why actual results might differ, whether as a result of new information, future events or otherwise, except as required by law.
Senior Director, Head of Corporate Communications
Chief Operating Officer and Chief Financial Officer
Robert H. Uhl