Kythera Biopharmaceuticals Inc. hit the bull's eye in two pivotal European Phase III trials of lead compound ATX-101, a first-in-class injectable drug to reduce what's commonly known as a double chin.

In a top-line analysis of the trial data, ATX-101 was well tolerated and met the pre-specified primary endpoints, demonstrating statistically significant reduction of moderate to severe submental fat compared to placebo, as assessed by a five-point Clinician-Reported Submental Fat Rating Scale (p < 0.001) and a seven-point Subject Satisfaction Rating Scale (p <0.001).

In both trials, ATX-101 also demonstrated statistically significant efficacy compared to placebo, as evaluated by secondary Patient-Reported Outcomes (p < 0.001). In addition, as an objective measure, calipers were used to confirm the reduction of submental fat thickness.

If approved, ATX-101 will be the first in a new class of injectable drugs to reduce fat under the chin without surgery. The compound would augment the aesthetics toolkit rather than competing head-to-head with Allergan Inc.'s market-leading Botox (onabotulinumtoxin A), potentially generating a comparable revenue stream.

Earlier this month, Leerink Swann analyst Seamus Fernandez predicted in a research report that Allergan's revenues from the use of Botox in the cosmetic dermatology space could grow from $363 million in 2011 to more than $600 million in 2018.

Kythera's ATX-101 is a proprietary formulation of synthetic sodium deoxycholate, a well-characterized endogenous compound involved in the natural breakdown of dietary fat that is selective for adipocytes and clears rapidly.

ATX-101 is injected into the submental area using small needles. The compound is designed to disrupt the membrane of fat cells, allowing the adipocytes – the storage units for triglycerides – to spill out into the extracellular space, where they are later cleaned up by the body. The area returns to normal in a few days, minus the fat cells.

The identical Phase III multicenter, randomized, double-blind, placebo-controlled trials enrolled 723 patients in 57 centers across the UK, France, Germany, Belgium, Spain and Italy. Patients received one of two dosing regimens (1 mg/cm2 or 2 mg/cm2) or placebo, administered monthly into the submental fat area for up to four treatment cycles, and were followed up for 12 weeks following treatment.

Adverse events were primarily mild to moderate and transient and included pain, swelling, numbness, bruising and induration. Those were limited to the injection site, and most were temporally associated with treatment. No systemic treatment-related adverse events were reported.

Kythera, of Calabasas, Calif., said it will present additional data from the trials at the American Society for Aesthetic Plastic Surgery meeting in May and at the Vegas Cosmetic Surgery International Multispecialty Symposium in June.

The complete data analysis will be reported later this year.

The Phase III results mirror the findings observed in Phase II trials, where ATX-101 was well tolerated and yielded statistically significant reduction of unwanted submental fat compared to placebo.

The clinical development of ATX-101 in Europe is a joint effort with Bayer HealthCare's dermatology unit, Intendis, which licensed the rights to ATX-101 outside the U.S. and Canada in a potential $373 million deal that includes royalties based on net sales and encompasses all possible indications. (See BioWorld Today, Sept. 1, 2010.)

Last month, Kythera initiated two pivotal Phase III trials of ATX-101 in the U.S. and Canada. Known as REFINE-1 and REFINE-2 (Randomized Double-blind Evaluation of Submental Fat Reduction IN ATX-101 TrEated Patients), the prospective, placebo-controlled trials plan to enroll 1,000 patients under an active U.S. registration program.

In September 2011, Kythera raised $37.4 million in a Series D, giving the company sufficient runway to complete the North American trial, which is expected to report data in the first half of 2013. (See BioWorld Today, Sept. 20, 2011.)

"The ideal situation for us was to get an ex-U.S. licensor but to keep the product ourselves in the U.S.," Keith Leonard, Kythera's president and CEO, told BioWorld Today at the time, adding that Kythera is aiming for a 2014 regulatory approval and plans to launch the product on its own in the U.S.

Company officials did not respond to interview requests Wednesday.

Although the market for minimally invasive cosmetic procedures is dominated by products like Botox and wrinkle fillers, biotechs and pharma companies are gaining a bigger foothold. (See BioWorld Today, April 26, 2011.)

In June 2011, for example, Fibrocell Sciences Inc.'s LaViv (azficel-T) was approved by the FDA to reduce the appearance of moderate to severe nasolabial fold wrinkles, commonly known as smile lines. (See BioWorld Today, June 23, 2011.)

The technology developed by Exton, Pa.-based Fibrocell marks the first personalized approach in the aesthetics space, but firms like Medicis Pharmaceutical Corp. and Ipsen SA also have pulled in impressive revenue by branching into nonmedical indications, proving that consumers are willing to pay out of pocket for FDA-approved image-improving agents. Kythera maintains an active research interest in hair and fat biology, pigmentation modulation and facial contouring, but Leonard previously told BioWorld Today that, for the time being, the company is focused exclusively on developing and commercializing its lead compound.