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Dermira Announces Positive Topline Results from Two Pivotal Phase 3 Clinical Trials for DRM04 in Patients with Primary Axillary Hyperhidrosis

MENLO PARK, Calif., June 01, 2016 (GLOBE NEWSWIRE) -- Dermira, Inc. (NASDAQ:DERM), a biopharmaceutical company dedicated to identifying, developing and commercializing innovative, differentiated therapies to improve the lives of patients with dermatologic diseases, today announced topline results from its Phase 3 ATMOS-1 and ATMOS-2 pivotal trials for DRM04, a topical anticholinergic product candidate in development for patients with primary axillary hyperhidrosis (excessive underarm sweating). Both clinical trials evaluated the safety and efficacy of DRM04 compared to vehicle.

In the ATMOS-2 trial, DRM04 demonstrated statistically significant improvements for both co-primary endpoints and both secondary endpoints compared to vehicle. In the ATMOS-1 trial, DRM04 demonstrated statistically significant improvements for one of the co-primary endpoints and both secondary endpoints. These results were based on the overall dataset from the intent-to-treat population. For the second co-primary endpoint in the ATMOS-1 trial, when extreme outlier data from one analysis center were excluded in accordance with the pre-specified statistical analysis plan submitted to the U.S. Food and Drug Administration (FDA), DRM04 demonstrated statistically significant results compared to vehicle. Consistent with previous results, DRM04 was generally well-tolerated with side effects that were primarily mild to moderate in severity.

Based on the results of these trials, Dermira plans to submit a New Drug Application (NDA) to the FDA for potential approval of DRM04. The NDA submission is targeted for the second half of 2017, subject to the completion of the Phase 3 ARIDO trial, an open-label trial assessing the long-term safety of DRM04, other registration-enabling activities and a pre-NDA meeting with the FDA.

“These results from the ATMOS-1 and ATMOS-2 trials bring us a step closer to offering DRM04 as a once-daily topical treatment for the millions of people who suffer from primary axillary hyperhidrosis, an undertreated skin condition,” said Tom Wiggans, chairman and chief executive officer of Dermira. “We are pleased with the efficacy and tolerability profile of DRM04 observed in these trials, particularly the improvements patients reported in their condition.”

The co-primary endpoints for the ATMOS-1 and ATMOS-2 Phase 3 trials 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. The secondary endpoints in both trials measured the proportion of patients who had at least a two-grade improvement from baseline as measured by the Hyperhidrosis Disease Severity Scale (HDSS) and the proportion of patients with at least a 50% reduction from baseline in gravimetrically-measured sweat production. Each endpoint was measured at the end of the four-week treatment period.

ATMOS-1 Results:

  • The proportion of patients who achieved at least a four-point improvement in sweating severity, as measured by the ASDD, was 52.8% in DRM04-treated patients, compared to 28.3% in patients who received the vehicle only (p<0.001).
  • The average reduction in sweat production was 104.9 mg in patients treated with DRM04 as compared to 91.9 mg in vehicle-treated patients based on the overall dataset from the intent-to-treat population (p=0.065). As outlined in the pre-specified statistical analysis plan submitted to the FDA, a sensitivity analysis was conducted that led to the exclusion of an analysis center with extreme outlier data for the gravimetric measurement of sweat. This analysis center consisted of 14 patients, of whom nine were treated with DRM04 and five received vehicle only. Following the exclusion of this analysis center, patients treated with DRM04 demonstrated an average reduction in sweat production of 96.2 mg as compared to 90.6 mg in patients who received the vehicle only (p=0.001).
  • The proportion of patients who achieved at least a two-grade improvement in HDSS score, a secondary endpoint, was 56.5% in patients treated with DRM04 as compared to 23.7% in patients who received the vehicle only (p<0.001).
  • The proportion of patients with at least a 50% reduction from baseline in gravimetrically-measured sweat production, a secondary endpoint, was 72.4% in patients treated with DRM04 as compared to 53.2% in patients who received the vehicle only (p<0.001).
  • In this trial, 229 patients were randomized to receive DRM04 and 115 patients were randomized to receive vehicle.

ATMOS-2 Results:

  • The proportion of patients who achieved at least a four-point improvement in sweating severity, as measured by the ASDD, was 66.1% in DRM04-treated patients, compared to 26.9% in patients who received the vehicle only (p<0.001).
  • The average reduction in sweat production was 110.3 mg in patients treated with DRM04 as compared to 92.2 mg in patients who received the vehicle only (p<0.001).
  • The proportion of patients who achieved at least a two-grade improvement in HDSS score, a secondary endpoint, was 61.6% in patients treated with DRM04 as compared to 27.8% in patients who received the vehicle only (p<0.001).
  • The proportion of patients with at least a 50% reduction from baseline in gravimetrically-measured sweat production, a secondary endpoint, was 77.3% in patients treated with DRM04 as compared to 53.3% in patients who received the vehicle only (p<0.001).
  • In this trial, 234 patients were randomized to receive DRM04 and 119 patients were randomized to receive vehicle.

“The results from these pivotal trials are very encouraging and demonstrate that DRM04 has the potential to be a new and differentiated treatment option for patients suffering from excessive underarm sweating,” said David Pariser, M.D., professor at Eastern Virginia Medical School, Department of Dermatology and one of the DRM04 Phase 3 clinical trial investigators. “Hyperhidrosis sufferers currently have limited treatment alternatives and, in my experience, are looking for new therapies that are effective and tolerable. Based on the efficacy and safety demonstrated in the Phase 3 trials, DRM04 may represent a convenient treatment option for patients living with this condition.”

Consistent with the results from the Phase 2 clinical program, DRM04 was generally well-tolerated with side effects that were primarily mild to moderate in severity.

The most frequently reported adverse events in the ATMOS-1 trial were dry mouth (18.9% and 3.5% for DRM04 and the vehicle only, respectively), application site pain (8.8% and 9.6%), dilated pupil (mydriasis; 6.6% and 0.0%), headache (4.4% and 2.6%), sore throat (oropharyngeal pain; 4.0% and 1.8%), upper respiratory tract infection (4.0% and 0.9%), blurred vision (3.5% and 0.0%), urinary hesitation (2.2% and 0.0%) and dry eye (0.9% and 0.0%). In the ATMOS-1 trial, 3.5% (8/229) of patients treated with DRM04 withdrew from the trial due to adverse events, compared to 0.9% (1/115) of patients who received vehicle only. There was one treatment-related serious adverse event reported in the ATMOS-1 trial for a patient treated with DRM04 who reported a dilated pupil.

The most frequently reported adverse events in the ATMOS-2 trial were dry mouth (29.3% and 7.6% for DRM04 and the vehicle only, respectively), application site pain (8.6% and 9.3%), dilated pupil (mydriasis; 6.9% and 0.0%), headache (5.6% and 1.7%), sore throat (oropharyngeal pain; 7.3% and 0.8%), upper respiratory tract infection (2.2% and 4.2%), blurred vision (3.4% and 0.0%), urinary hesitation (4.7% and 0.0%) and dry eye (3.9% and 0.8%). In the ATMOS-2 trial, 3.8% (9/234) of patients treated with DRM04 withdrew from the trial due to adverse events, compared to 0.0% (0/119) who received vehicle only. 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.

The data will be submitted for presentation at an upcoming medical conference and for consideration in a peer-reviewed medical journal.

About the DRM04 Phase 3 Clinical Program

ATMOS-1 and ATMOS-2 were designed as identical, multi-center, randomized, double-blind, vehicle-controlled trials to assess the safety and efficacy of DRM04 at a concentration of 3.75% compared to vehicle in adolescent and adult patients (ages nine and older) with primary axillary hyperhidrosis. The ATMOS-1 trial enrolled 344 patients at 29 sites in the United States and Germany, and the ATMOS-2 trial enrolled 353 patients at 20 sites in the United States. Inclusion criteria required that prior to the start of treatment, all patients produce at least 50 mg of sweat in each underarm over a five-minute period and rate the severity of their sweating as a four or higher on the 11-point ASDD scale and as a three or a four on the four-grade HDSS. In the ATMOS-1 trial, 229 patients were randomized to receive DRM04 and 115 patients were randomized to receive vehicle; and in the ATMOS-2 trial, 234 patients were randomized to receive DRM04 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 DRM04 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 ASDD and the average absolute change from baseline in gravimetrically-measured sweat production. Dermira developed and validated the ASDD instrument in accordance with the 2009 FDA guidance document for PRO instruments. The ASDD endpoint, a four-point change on an 11-point scale, was selected based on analyses of data generated in a second Phase 2b trial, DRM04-HH02, and feedback from the FDA. For the sweat production endpoint, sweat production was assessed in each patient as the average of the amounts of sweat produced in each underarm during a five-minute period. The two secondary endpoints in the trials measured the proportion of patients who had at least a two-grade improvement from baseline as measured by HDSS and the proportion of patients with at least a 50% reduction from baseline in gravimetrically-measured sweat production. Both the primary and secondary endpoints were assessed at the end of the four-week treatment period.

In addition to the ATMOS-1 and ATMOS-2 trials, Dermira is also conducting ARIDO, an open-label trial assessing the long-term safety of DRM04 as part of its Phase 3 program to provide safety data for a minimum of 100 patients who have received DRM04 for at least 12 months per the International Council on Harmonization guidelines. Patients from the ATMOS-1 and ATMOS-2 trials were permitted to enroll in the ARIDO trial and continue to receive DRM04 (active treatment) for up to an additional 44 weeks from the end of the four-week treatment periods in the ATMOS-1 or ATMOS-2 trials. A total of 564 patients, more than 80%, elected to enroll in ARIDO. Dermira expects to complete the treatment period for the ARIDO trial by the end of 2016.

About Hyperhidrosis

Based on the most recent data available in the United States, the prevalence of hyperhidrosis in 2003 was estimated to be 2.8% of the population, or approximately 7.8 million people. 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 known as a 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. According to published studies, approximately half of hyperhidrosis sufferers have axillary hyperhidrosis, and roughly one-third of axillary hyperhidrosis sufferers, or 1.3 million Americans, have severe disease that is barely tolerable and frequently interferes with daily activities or is intolerable and always interferes with daily activities as scored by the HDSS. Several studies have demonstrated that excessive sweating often impedes normal daily activities and can result in occupational, emotional, psychological, social and physical impairment.

About DRM04

DRM04 is a topical anticholinergic product currently in clinical development for the treatment of primary axillary hyperhidrosis. DRM04 is designed to block sweat production by inhibiting the interaction between acetylcholine and the cholinergic receptors responsible for sweat gland activation.

About Dermira

Dermira is a biopharmaceutical company dedicated to identifying, developing and commercializing innovative, differentiated therapies to improve the lives of patients with dermatologic diseases. Dermira’s portfolio includes three late-stage product candidates that target significant unmet needs and market opportunities: CIMZIA® (certolizumab pegol), in Phase 3 development in collaboration with UCB Pharma S.A. for the treatment of moderate-to-severe chronic plaque psoriasis; DRM04, in Phase 3 development for the treatment of primary axillary hyperhidrosis (excessive underarm sweating); and DRM01, in Phase 2b development for the treatment of facial acne vulgaris. Dermira is headquartered in Menlo Park, California. For more information, please visit www.dermira.com.

In addition to our filings with the Securities and Exchange Commission (SEC), press releases, public conference calls and webcasts, we use our website (www.dermira.com) and LinkedIn page (https://www.linkedin.com/company/dermira-inc-) as channels of distribution of information about our company, our product candidates, our planned financial and other announcements, our attendance at upcoming investor and industry conferences and other matters. Such information may be deemed material information and we may use these channels to comply with our disclosure obligations under Regulation FD. Therefore, investors should monitor our website and our LinkedIn page in addition to following our SEC filings, press releases, public conference calls and webcasts.

Forward-Looking Statements

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 the use of DRM04 as a potential new, safe, convenient, differentiated and effective treatment for hyperhidrosis; the expected timing for completion of the treatment period for the open-label ARIDO Phase 3 trial and the results of such trial; the timing of the anticipated pre-NDA meeting with the FDA and the timing of other registration-enabling activities; and the timing and submission of an NDA to the FDA for DRM04. These statements deal with future events and involve known and unknown risks, uncertainties and other factors that may cause our 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 our open-label ARIDO Phase 3 trial; our anticipated pre-NDA meeting with the FDA for DRM04; our dependence on third-party clinical research organizations, manufacturers and suppliers; our ability to obtain regulatory approval for our product candidate; and our ability to continue to stay in compliance with applicable laws and regulations. For a discussion of important factors that may cause our actual results to differ materially from those expressed or implied by our forward-looking statements, you should refer to the section entitled “Risk Factors” set forth in our Annual Report on Form 10-K, Quarterly Report on Form 10-Q and other filings we make with the SEC from time to time. Furthermore, such forward-looking statements speak only as of the date of this press release. We undertake 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.

Source: Dermira, Inc.

Posted: June 2016

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