A simple injection in the neck to get rid of that double chin? Sounds too good to be true, and that very well may be the case concerning Bayer's newest fat-dissolving injectable, ATX-101, which is beginning phase III trials in Europe.
The upcoming multi-center, randomized, double-blind, placebo-controled study will test the efficacy of ATX-101 for eliminating localized fat under the chin, known as submental fat. The companies announced Monday that they are enrolling patients for the trial in France, Germany, Belgium, Spain, Italy and the U.K.
The drug utilizes half of the two-drug, off-label cocktail used for the notoriously problematic fat-dissolving injectable Lipodissolve that prompted a public warning by the Food and Drug Administration in spring 2010.
Lipodissolve, which was marketed as a quick and easy "lunchtime lipo" procedure a few years back, utilized two chemicals, phosphatidylcholine (PC) and deoxycholate (DC), neither of which were FDA approved for fat elimination.
ATX-101, is just sodium deoxycholate (DC in solution).
Research has shown PC actually inhibits the fat-dissolving effects of DC, so researchers are testing the efficacy of DC alone for fat elimination, said KYTHERA Biopharmaceuticals, Inc., which teamed with Bayer in August 2010 for the upcoming trial.
KYTHERA hopes ultimately to bring an FDA-approved compound for injectable fat elimination to the U.S. market. Two phase II trials in humans have been done in the U.S. so far and a third is underway.
"We are very pleased with the progress that has been made in Europe with ATX-101," Keith Leonard, KYTHERA's president and CEO, said in a press release on the trial. "The initiation of these Phase III studies marks an important milestone in our collaboration with Intendis and further demonstrates the potential of ATX-101 as a first-in-class injectable drug for localized fat reduction."
But plastic surgeons are wary of this renewed attempt to test DC as a cosmetic fat-dissolver.
"I would be very cautious. Even if it's approved in Europe, people will start purchasing it and sneaking into the U.S. illegally," said Dr. Darrick Antell, a plastic surgeon at Roosevelt Hospital in New York and a spokesman for the American Society of Plastic Surgeons. "There's no doubt in my mind that if it's approved for the small area [under the chin], then people will start using for large areas and I have no doubt that there will invariably be adverse effects. [Injectable fat-dissolvers] need a lot more work. People who would use this sort of medicine at this point would be like driving ahead of your headlights."
The story of a fat-disolving injectable began with a drug called Lipostabil, approved for use in Germany, that was found to be effective at breaking down fatty buildup in the arteries known as atherosclerosis. When it was noted that Lipostabil may dissolve fat under the skin as well as in the arteries, people in the U.S. began approximating the drug (which was not approved in the U.S.) by combining its main ingredients, DC and PC and injecting it into fatty areas like the abdomen.
This combination, which became known as Lipodissolve, was not regulated, however, and the ingredients in any given injection were not standardized.
Because neither ingredient was approved by the FDA for fat elimination and the combination was not approved for anything in the U.S., use of Lipodissolve was a "double concern," said Dr. Malcolm Roth, director of plastic surgery at Maimondes Medical Center in Brooklyn, N.Y., and president-elect of the American Society of Plastic Surgeons.
"Infection, gangrene of the skin, scarring ,chronic pain and deformity are some of the adverse effects seen," said Roth.
"Some also experienced hard lumps where the fat cells had died and clumped together," added Antell.
Ultimately the FDA issued warnings to the public not to use Lipodissolve, and the combination was banned in Canada and Brazil.
It wasn't the combination that was dissolving fat however, noted Dr. Carolyn Jacob, director of Chicago Cosmetic Surgery and Dermatology, it was the DC alone.
Thus, with the trials of ATX-101, Bayer and KYTHERA are testing the safety and efficacy of using a DC solution, sodium deoxycholate, from controlled sources in hopes of producing an injectable that can get regulatory approval in the United States and abroad.
How would deoxycholate work?
Deoxycholate is a common ingredient in soap, that "you'd probably find in your laundry detergents," said Antell. "What soaps do in your laundry detergent is ... help dissipate fatty tissue so that you can get grease and oil stains out of your clothing."
The breakdown of fatty tissue is purportedly the same thing that's happening in the body when DC is injected subcutaneously.
"But you have to wonder: Where does that dissolved material go?" asked Antell.
Roth echoed the concerns, questioning whether small bits of fatty tissue could do damage to the liver, clog the arteries or potentially cause a stroke if they make their way to the brain through the blood stream.
Because there are existing means of breaking down fat using cooling that have not shown signs of adverse effect, Jacob said, "I'm less concerned about what happens to the dissolved fat as what happens when the medication seeps into the surrounding areas, possibly causing breakdown of the skin or other tissues."
This becomes a greater concern if DC is injected into large areas such as the abdomen and buttocks, despite the fact that it only currently is being tested for use in the small under-chin area.
Jacob, Antell and Roth said that if ATX-101 gets approved for ameliorating double chins, it undoubtedly would be used off-label for other larger, untested areas of the body.
"Any time there is an injection [for fat loss], there will be tremendous temptation for people to abuse it and possibly inject themselves," Antell said. "We all like minimally invasive surgeries, but it's still wait and see at this point [for ATX-101]. I would be very cautious."