Montreal — Sodium deoxycholate, an injectable therapy under study known as ATX-101 (Kythera) and not yet approved by the Food and Drug Administration, will present a noninvasive treatment option for patients who are concerned about the appearance of their submental fat or “double chin.”
Surgical correction including liposuction, necklift and jawlift remain the gold standard for treating the double chin, but Shannon Humphrey, M.D., F.R.C.P.C., F.A.A.D., a dermatologist and clinical assistant professor, department of dermatology and skin science, University of British Columbia, Vancouver, notes that the treatment of the submental region involves more than just eliminating submental fat.
“It is more than the double chin being perceived as unattractive,” says Dr. Humphrey, speaking here at an update on the newest in therapeutics in dermatology. “If you look along the jaw line, there is a loss of definition for these patients. What patients are most impressed with is a newly-defined chin and jaw line that they had not seen in many years (with this treatment).”
Dr. Humphrey stresses that it is not only overweight patients who may have a pocket of fat under their chins. “There are some patients for whom it is genetically determined,” she says.
Definition along the mandible has been regarded as a perennial attribute of attractiveness, Dr. Humphrey notes. “We only have to look at the iconic bust of Nefertiti,” says Dr. Humphrey, referencing the historical figure regarded as Egypt’s most beautiful queen.
In the appropriately selected patient with submental fat who is seeking an improved appearance, a neuromodulator can be administered along the jaw line and provide elevation of the submental skin (Nerfertiti lift).
“It is helpful for a subset of patients who do not have advanced skin laxity,” Dr. Humphrey says.
As a proprietary formulation of deoxycholic acid, a bile salt that naturally occurs in the body, ATX-101 has been studied in clinical trials in Europe and in North America, with results most recently presented at this year’s meeting of the American Society of Dermatologic Surgery (ASDS) in Chicago. Two identical phase 3 pivotal trials met all of their predefined primary and secondary endpoints and demonstrated high statistical significance across these measures (P<0.001).
The mechanism of action is adipocytolysis and preferential targeting of cells with low protein content (adipocytes), according to Dr. Humphrey, of the injectable is that it preferentially affects the cells that contain low protein content. “The blood vessels, nerves, and muscles are relatively unaffected,” she says.
Early clinical research revealed that there was actual breakdown or destruction of the fat cells, followed by inflammation, macrophage infiltration and fibroblasts, eventually leading to neo-collagenesis or new formation of collagen, which would have a positive effect for patients that may have submental laxity, according to Dr. Humphrey.
The treatment is performed with a 30-gauge needle that is injected subcutaneously into the submental fat, Dr. Humphrey says. Patients undergo a series of multiple injections into the fat under the chin, at intervals of one month apart.
“Each depot of liquid that is injected is about 0.2ccs,” Dr. Humphrey says. “It is designed to be performed in multiple treatments.”
Using a Clinician Reported Submental Fat Rating Scale (CR-SMFRS), European investigators found a statistically significant difference in submental fat at 32 weeks, about three months after the last treatment. Patients who were injected with saline also saw benefit from injection, Dr. Humphrey notes. Treated patients saw no difference in skin laxity.
Both primary and secondary endpoints in two phase 3 trials, such as an improvement of at least one grade from baseline on the CR-SMFRS and Patient Reported-Submental Fat Rating Scale (PR-SMFRS), were achieved. At this year's ASDS meeting, additional data revealing high rates of patient satisfaction were disclosed.
The downside of the treatment is the discomfort patients experience during treatment. Post-treatment patients can experience swelling and bruising. In some instances, patients have experienced numbness for several months.
“There needs to be a discussion with patients in terms of expectations,” Dr. Humphrey says.
The maker of ATX-101 plans a submission to the FDA, she notes.
“ATX-101 will be a first in class injectable drug for submental fat reduction and a useful addition to our therapeutic armamentarium for contouring the submental region,” she says.
Disclosures: Dr. Humphrey is conducting trials on ATX-101 for Kythera Biopharmaceuticals.