A compound approved for use in asthma inhalers is reported to begin phase 3 trials during the first half of 2015 for use as an injectable option in fat reduction and body contouring. LIPO-202 (Neothetics) is a physician-administered injectable form of salmeterol xinafoate, a beta-2 adrenergic receptor, which, says researchers, not only helps asthmatics breathe better but also shrinks fat cells.
Dr. PeredoMarina Peredo, M.D., a dermatologist in Manhattan and Long Island, N.Y., and clinical investigator for LIPO 202, says physicians can perform the nonsurgical procedure in less than five minutes. The procedure includes making 20 injections, about 4 cm apart, at the site of an abdominal fat bulge. Patients come back weekly, for a total of eight weeks. Often by the first month, she says, they notice a circumference change in their bodies. It’s painless and requires no downtime.
“I think this product is going to do to body contouring or body sculpting what Botox did to facelifts,” Dr. Peredo says.
IN THIS ARTICLE:
LIPO-202 Phase 2 Results
Dr. NestorBased on the clinical phase 2 studies, LIPO-202 is effective at reducing abdominal fat and has a side effect profile virtually identical to placebo, says Mark Nestor, M.D., Ph.D., a clinical investigator in LIPO-202 phase 2 clinical trials and co-chair of Neothetics’ scientific advisory board.
ATX-101 receives unanimous support for FDA approval
“Patients in the study appear to be very satisfied with the results,” says Dr. Nestor, director for the Center for Clinical and Cosmetic Research and the Center for Cosmetic Enhancement in Aventura, Fla., and voluntary associate professor, dermatology and cutaneous surgery, University of Miami Miller School of Medicine, Miami, Fla.
Neothetics, formerly Lithera, announced results from its phase 2b RESET clinical study of LIPO-202 in a September 30, 2013, press release. Researchers tested three doses (0.4, 1.0 and 4.0 µg) in a multicenter, randomized, placebo-controlled trial, including 513 healthy, nonobese people with abdominal bulging due to excess subcutaneous fat.
Ideal candidates were those bothered by slight to moderate abdominal bulges, according to Dr. Peredo. “If they were too heavy, this was not an indication, at least for this particular study,” she says.
An additional exclusion criterion was use of inhalers because it’s the same medication, according to Dr. Peredo.
Researchers found the optimal treatment dose was 0.4 µg (20 times 0.02 µg/mL). Adverse events with LIPO-202 were generally mild, transient and similar to placebo. The most common adverse event was injection site reactions, according to the press release, and no patients withdrew from the study for this reason.
As for efficacy, “Responder analyses using a composite endpoint of a patient self-assessment (5-point verbal Patient Global Abdominal Profile Scale – P-GAPS) plus a clinician rating of abdominal contour (6-point visual Clinician Photo-numeric Scale – CPnS) demonstrated significant efficacy of LIPO-202 at the 0.4 µg dose versus placebo…,” according to the release.
Patients in the treatment group showed a mean reduction in circumference at the umbilicus of 1.6 cm versus 0.65 cm for placebo. The average reduction in abdominal volume in the treatment zone was 192 cc for the 0.4 µg LIPO-202 dose versus 68 cc for placebo.
Salmeterol Safety Profile
The inhaled form of salmeterol, one of the medicines found in Advair (GSK), has a list of side effects ranging from the more common — shortness of breath and chest tightness — to the more dangerous, including irregular heartbeat. Unexplained weight loss is one of the less common side effects.
Dr. Nestor says salmeterol xinafoate is a widely used, very safe medication for lung disease and has been approved for that indication for many years.
“Studies have shown a side effect profile similar to placebo when inhaled directly resulting in much higher blood levels than can be achieved by the amount utilized in clinical trials for fat reduction. Phase [2] studies have confirmed the exceptional safety profile of [salmeterol xinafoate],” Dr. Nestor says.
Shrinking Fat – Specs
LIPO-202 is intended for limited volume liposuction.
Salmeterol xinafoate is a beta-2 adrenergic receptor, and beta-2 receptors are found in fat cells, says Dr. Peredo. “Injecting this substance bolsters metabolism. We’re not killing fat cells; we’re actually just shrinking them,” she says.
The drug in LIPO-202 diffuses about 2 cm in radius, according to company literature. Physicians inject LIPO-202 with a 30-gauge, half-inch needle.
It’s not clear, according to Dr. Peredo, just how long it takes for patients to notice results. Anecdotally, she says, many have come to her after four sessions commenting they had gone down a jean size.
It’s also too early to tell how long the effects of LIPO-202 treatment last.
“The way the [phase 2] study was designed, we only did it for eight weeks. Now, in the phase 3, we’re going to follow patients longer,” Dr. Peredo says.
LIPO-202 vs Liposuction
As any cosmetic doctor who has experience with liposuction knows, it can be a labor-intensive procedure. “I would just do one case per day because I’d be exhausted,” says Dr. Peredo.
Liposuction also requires patients to take time off of work and for the practice to make large practice investments.
“My malpractice insurance tripled when I was doing liposuction. I had to have a whole OR, a recovery room. With Zeltiq [CoolSculpting], there are also equipment costs, you need room and have to pay for consumables. With LIPO-202, I don’t know how it’s going to be priced, but it’s pretty much just a syringe,” says Dr. Peredo.
But there’s also the familiar tradeoff. Results with LIPO-202 are not nearly as dramatic as those achieved with traditional liposuction and not even as dramatic as results from CoolSculpting, which is also painless and requires no downtime, she says.
“The limitation with CoolSculpting is if they don’t have enough fat to suction with the applicator, they are not candidates,” Dr. Peredo says.
If approved, LIPO-202 could be a stand-alone procedure for localized fat bulges. Conceivably, those might be anywhere on the body, but studies to date are limited to the abdominal region, according to Dr. Peredo.
“I believe that future studies could show additional efficacy in other body areas such as the arms and neck [submental],” Dr. Nestor says.
LIPO-202 could also be an adjunct to CoolSculpting or liposuction for patients who achieve less-than-perfect results. Rather than go back for touchups with another invasive procedure, the physician might use LIPO-202, she says.
LIPO-202 isn’t the only injectable product seeking FDA approval for fat reduction. Kythera Biopharmaceuticals is expecting possible FDA approval for the reduction of submental fat as soon as this May. ATX-101 is a purified synthetic deoxycholic acid, a molecule in the body that helps break down dietary fat.
