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KYTHERA Announces Positive ATX-101 Top Line Phase III Trial Results for the Reduction of Submental Fat

September 16, 2013

KYTHERA Announces Positive ATX-101 Top Line Phase III Trial Results for the Reduction of Submental Fat

- REFINE-1 and REFINE-2 Trials Demonstrate Statistically Significant Results for Primary and Secondary Endpoints -

Calabasas, Calif., September 16, 2013 – KYTHERA Biopharmaceuticals, Inc. (NASDAQ: KYTH) today announced that its ATX-101 REFINE-1 and REFINE-2 Phase III trials met all primary and secondary endpoints. These two pivotal Phase III trials were conducted in the U.S. and Canada to compare the efficacy and safety of a 2 mg/cm2 dose of ATX-101 versus placebo for the reduction of submental fat, which commonly presents as a double chin. ATX-101 is a proprietary formulation of a purified synthetic version of deoxycholic acid, a naturally occurring molecule in the body that aids in the breakdown of dietary fat.[1] If approved, it will be a first-in-class submental contouring injectable drug.

REFINE-1 and REFINE-2 are two identical multicenter, double-blind, randomized, placebo-controlled trials that enrolled more than 1,000 subjects with moderate to severe submental fat in 70 centers in the U.S. and Canada. Validated clinician- and patient-rating scales were used to evaluate primary efficacy endpoints, assessed 12 weeks after the last treatment.

Primary Endpoints

REFINE-1 (Study ATX-101-11-22)

  • 70.3 percent of ATX-101 (2mg/cm2) REFINE-1 subjects demonstrated a simultaneous improvement of at least one grade from baseline on the Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) and Patient-Reported Submental Fat Rating Scale (PR-SMFRS) vs. 18.7 percent in placebo (p<0.001).

  • 13.4 percent of ATX-101 (2mg/cm2) REFINE-1 subjects demonstrated a simultaneous improvement of at least two grades from baseline on the Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) and Patient-Reported Submental Fat Rating Scale (PR-SMFRS) vs. 0 percent in placebo (p<0.001).

REFINE-2 (Study ATX-101-11-23)

  • 66.9 percent of ATX-101 (2mg/cm2) REFINE-2 subjects demonstrated a simultaneous improvement of at least one grade from baseline on the Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) and Patient-Reported Submental Fat Rating Scale (PR-SMFRS) vs. 22.4 percent in placebo (p<0.001).

  • 18.7 percent of ATX-101 (2mg/cm2) REFINE-2 subjects demonstrated a simultaneous improvement of at least two grades from baseline on the Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) and Patient-Reported Submental Fat Rating Scale (PR-SMFRS) vs. 3.2 percent in placebo (p<0.001).

“The strong results from REFINE-1 and REFINE-2 are incredibly exciting and consistent with the profile of ATX-101 based on previous data,” said Frederick Beddingfield, III, M.D., Ph.D., Chief Medical Officer, KYTHERA Biopharmaceuticals, Inc. “We look forward to discussing submission plans with U.S. and Canadian regulatory authorities in the near future. If approved, ATX-101 will represent a significant innovation in the category of aesthetic medicine.”

Secondary Efficacy Endpoints

Additionally, an assessment of the trials’ first secondary endpoint showed 46.6 percent of REFINE-1 and 40.0 percent of REFINE-2 patients achieved a predefined, statistically significant reduction in the volume of their submental region vs. 5.4 and 5.1 percent for placebo, respectively (both p<0.001), as measured through magnetic resonance imaging (MRI). 

Subjects also rated the visual and psychological impacts of submental fat using the Patient-Reported Submental Fat Impact Scale (PR-SMFIS), which assessed whether they perceived themselves to be happier, less bothered, less self-conscious, less embarrassed, younger or less overweight after treatment with ATX-101. Statistical significance was achieved for the change from baseline in PR-SMFIS with 3.63 vs. 1.14, and 3.47 vs. 1.48, for ATX-101 (2mg/cm2) and placebo for REFINE-1 and REFINE-2, respectively (p<0.001 for both). Each individual component within the PR-SMFIS also demonstrated statistical significance vs. placebo in both trials (p<0.001 for all PR-SMFIS measures).

“The area under the chin is important to patients as it impacts overall facial harmony, balance and attractiveness; however, an undesirable double chin is often undertreated by aesthetic physicians as there is no proven non-surgical option to effectively reduce submental fat,” said Jean D. Carruthers, M.D., FRCSC, FRC, REFINE-1 investigator and Clinical Professor, Department of Ophthalmology, University of British Columbia, Vancouver. “ATX-101 could provide a solution that fulfills this unmet need and become an important addition to the overall practice of aesthetics.”

Safety

There were no treatment-related serious adverse events. The most common adverse events, which were predominantly mild to moderate, were swelling, pain, bruising, numbness and redness. Consistent with previous studies, these adverse events were predominately transient and local to the treatment area. Less than 4 percent of subjects discontinued the study due to adverse events.

Upcoming Scientific Presentation

Additional information from these studies will be reported at the upcoming American Society for Dermatologic Surgery (ASDS) annual meeting, October 3-6 in Chicago.

Conference Call

KYTHERA will host an investor conference call and webcast to discuss the results at 8:00 AM (Eastern Time) on September 17, 2013. Presenting from the Company will be Keith Leonard, President and CEO, and Dr. Frederick Beddingfield, III, Chief Medical Officer.

Individuals interested in participating in the call should dial (877) 344-3890 (U.S. and Canada) or (760) 666-3770 (international) using conference ID number 65266554. To access the webcast, please visit the Investors section of KYTHERA's website at www.kytherabiopharma.com at least 15 minutes prior to the start of the call to ensure adequate time for any software downloads that may be required. A PDF of reference slides will be available during the call.

The call will be available for replay via telephone starting September 17, 2013 at approximately 11 a.m. PDT, running through 11:59 p.m. PDT on October 1, 2013. To listen to the replay, dial (855) 859-2056 (U.S. and Canada) or (404) 537-3406 (international) using conference ID number 65266554. The archived webcast will be available on KYTHERA's website for 14 days beginning approximately one hour after the call has completed.

About REFINE-1 and REFINE-2

REFINE-1 and REFINE-2 (studies ATX-101-11-22 and ATX-101-11-23) are two identical multicenter, double-blind, randomized, placebo-controlled Phase III pivotal trials conducted to compare the efficacy and safety of a 2 mg/cm2 dose of ATX-101 versus placebo for the reduction of submental fat. Patients received up to six treatments approximately 28 days apart. REFINE-1 and REFINE-2 were conducted at 70 centers in the U.S. and Canada and enrolled 506 and 516 patients, respectively, with moderate to severe submental fat at baseline as determined through both validated clinician- and patient-rating scales. The two co-primary efficacy endpoints of the trial were: 1) proportion of patients with a simultaneous improvement of at least one grade from baseline on the Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) and the Patient-Reported Submental Fat Rating Scale (PR-SMFRS); and 2) proportion of patients with a simultaneous improvement of at least two grades from baseline on the CR-SMFRS and the PR-SMFRS. Secondary endpoints included the reduction in volume of the submental region as measured using magnetic resonance imaging (MRI), and improvement in the appearance-related impacts of submental fat, assessed using the Patient-Reported Submental Fat Impact Scale (PR-SMFIS).   

About ATX-101

ATX-101 is currently in late stage clinical trials for the reduction of submental fat, which commonly presents as a double chin. It is a proprietary formulation of a purified synthetic version of deoxycholic acid, a naturally occurring molecule in the body that aids in the breakdown of dietary fat.[2]

The submental region, or the area under the chin, is visually important to patients, but is often undertreated. ATX-101 treatment contours the area under the chin by destroying fat cells while leaving surrounding tissue largely unaffected.

For the past six years, ATX-101 has been the focus of a global clinical development program that has enrolled more than 2,500 patients worldwide, of which more than 1,500 have been treated with ATX-101. If approved, ATX-101 will be a first-in-class submental contouring injectable drug.

Bayer HealthCare holds development and commercialization rights to ATX-101 outside of the U.S. and Canada.

About KYTHERA Biopharmaceuticals, Inc.

KYTHERA Biopharmaceuticals, Inc. is a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of novel prescription products for the aesthetic medicine market. KYTHERA’s product candidate, ATX-101, is currently in late stage clinical trials for the reduction of submental fat, which commonly presents as a double chin. If approved, it will be a first-in-class submental contouring injectable drug. KYTHERA also maintains an active research interest in hair and fat biology, pigmentation modulation and facial contouring. Find more information at http://www.kytherabiopharma.com.

Forward-Looking Statements

To the extent that statements contained in this press release are not descriptions of historical facts regarding KYTHERA, they are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, including that the topline results of the REFINE-1 and REFINE-2 trials for ATX-101 are indicative of the final results of the respective studies, the potential for ATX-101 to enter the market as the only FDA-approved drug for the reduction of submental fat and the commercial potential of ATX-101. Such forward-looking statements involve substantial risks and uncertainties that could cause our clinical development programs, future results, performance, or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainties inherent in the clinical drug development process, the regulatory approval process, the development progress of our collaborative partners, our substantial dependence on ATX-101 and other matters that could affect the availability or commercial potential of our drug candidate. KYTHERA undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of the Company in general, see KYTHERA’s reports filed with the Securities and Exchange Commission, including its Quarterly Report on Form 10-Q for the quarter ended June 30, 2013 and our Annual Report on Form 10-K for the year ended December 31, 2012.



[1] [2] Stryer L. Biosynthesis of membrane lipids and steroids. In: Biochemistry. New York, NY: WH Freeman and Co; 1995:691-707.