FDA Advisers Back New Injectable for Double Chins

Alicia Ault

March 09, 2015

A US Food and Drug Administration (FDA) advisory committee unanimously voted today to recommend approval of a new injectable to help reduce double chin.

The Dermatologic and Ophthalmic Drugs Advisory Committee said that Kythera Biotherapeutics' ATX-101 (deoxycholic acid) injection for improvement in the appearance of moderate-to-severe convexity or fullness associated with submental fat in adults is safe and effective.

If the FDA follows its panel's advice, ATX-101 would be the first injectable approved for submental fat contouring.

The committee members praised Kythera's work with the FDA and its development program for ATX-101, a patented formulation of a pure, nonanimal-derived version of deoxycholic acid, which is an endogenous molecule that aids in the breakdown of dietary fat.

The injection takes about 15 minutes. Once injected, ATX-101 physically disrupts the cell membrane, causing the destruction of fat cells. Macrophages eliminate cell debris, and eventually there is an increase in total collagen. The product would be indicated for up to six sessions at least a month apart.

Panel members and dermatologists who spoke at the public hearing said that patients want and need such a product.

"It's been clearly identified that there's an unmet clinical need," said committee chair Lynn A. Drake, MD, a dermatologist and lecturer at Harvard Medical School. She said that appearance plays into self-esteem and confidence, which are important. "Just because you're not having a heart attack and dying doesn't mean it's not important to you," said Dr Drake.

Washington, DC, dermatologist Tina Alster, MD, agreed, and noted that a recent survey had shown that 70% of consumers are somewhat to extremely bothered by a double chin. While there are other FDA-approved therapies, including liposuction, "These patients are seeking minimally invasive procedures," said Dr Alster, who was not compensated by Kythera.

ATX-101 was tested in two double-blind, randomly assigned, placebo-controlled trials of just over 1000 patients. Placebo patients received sham injections. All patients received up to six treatments, with 28 days in between injections.

In both trials, at 12 weeks after the last treatment, 13% to 19% of ATX-101 patients had at least a two-grade improvement on both the Clinician-Reported Submental Fat Rating Scale and the Patient-Reported Submental Fat Rating Scale compared with 3% for placebo patients. At least 70% of ATX-101 patients had at least a one-grade improvement.

Those scales were developed and validated by Kythera in conjunction with the FDA. The agency said that both efficacy measures were statistically significant.

ATX-101 was also effective and statistically significant on two secondary endpoints — magnetic resonance imaging scans of fat reduction and on a patient-rated overall appearance scale that was also developed by Kythera.

Safety and Off-Label Use Concerns

The FDA and Kythera both reported that most patients had injection-related side effects, such as edema, bruising, and numbness, but, by and large, they were not serious. The agency was more concerned about marginal mandibular nerve injury, seen in 4% of ATX-101 patients but only in 1% of placebo patients. The injuries spontaneously resolved, but lasted as long as 298 days.

There was also a concern about dysphagia, seen in 2% of ATX-101 patients but in less than 1% of placebo patients. Again, there were no lasting effects, with four years of follow-up.

Sidney Wolfe, MD, founder and senior adviser to Public Citizen's Health Research Group, said that the nerve damage was not adequately explained by Kythera. He urged the panel to require the company to study the potential for nerve injury, focusing on a potential mechanism of action. "We do not know about what the cause of the nerve damage is," said Dr Wolfe.

He also said that ATX-101 is likely to have off-label use and thus put other nerves at risk.

Kythera said it is recommending against use in other body parts — love handles or other large-treatment areas — and that it will seek a maximum-recommended dosage of 100 milligrams. The company will also have a training program for clinicians that emphasizes proper use, said Frederick C. Beddingfield III, MD, PhD, Kythera's chief medical officer.

"Training has surfaced as a major, major issue," said Dr Drake, the panel chair.

"We look forward to working with the FDA as they continue their review of ATX-101, with the goal of providing patients with the first and only approved non-surgical treatment for submental fullness," said Dr Beddingfield, in a statement released after the meeting.

The FDA is scheduled to make its final decision by May 13. Kythera is seeking approval also in Canada, Switzerland, and Australia.


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