Botulinum toxin in topical form draws interest

Key Points

National report - Much about it is still somewhat of a mystery, but early findings on a topical form of botulinum toxin have been compelling enough to earn a $20 million show of support from Medicis and catapult the research onto the cosmetic medicine radar.

The botulinum toxin molecule is large - very large - and just how the molecule could penetrate the stratum corneum and make its way deep enough under the skin to have the same effect as injected botulinum toxin has many scratching their heads.

Even the company behind the research, Mountain View, Calif., Revance Therapeutics, hasn't quite figured it out yet.

The details of what Revance does know about the vehicle are still largely under wraps, but a preliminary study that is the first published research on the formulation refers to the vehicle as a "proprietary transport peptide molecule that binds the toxin in a noncovalent manner."

The randomized, blinded, vehicle-controlled study yielded impressive results: A 65 percent mean reduction of sweating on 10 axillae treated with the BTX-A (200 U) was observed after four weeks of treatment, compared with a 25 percent mean reduction in sweating on the vehicle-controlled axillae (Derm Surg. 2007 Jan;33(1 Spec No.):S76-80).

Results promising

Lead author Richard Glogau, M.D., says the results offered an encouraging indication of the mechanism's potential.

"The issue we were concerned about was whether the material would actually get deep enough to reach the muscle," says Dr. Glogau, a clinical professor of dermatology at the University of California, San Francisco.

"But we obviously got to the bottom of the dermis, because that's where the endocrine sweat glands are."

Another concern, particularly in cosmetic use of the product, was the possibility of migration, but Dr. Glogau says so far, that doesn't appear to be an issue.

"It really appears to behave in a similar fashion as an injectable, and when applied topically, it stays local," he says.

According to Mr. Browne, "The initial formulations were sort of water-based, but that had the tendency to run away from the treatment site, so we moved to a gel base.

"(This) gives the control to apply the drug product exactly on the treatment site for targeted local superficial delivery."

U.S. trials awaited

Early clinical trials in Korea and Mexico have shown encouraging results, and Mr. Browne says he expects phase 2 clinical trials to begin in the United States sometime this year.

A big vote of confidence indicating that Revance may be more than just another bogus "better than Botox" product was Medicis' $20 million investment in the company, made in December.

The investment gave Medicis preferred stock in Revance, equivalent to about a 10 percent ownership of the company. Medicis also purchased an option to acquire Revance or gain exclusive North American licensing rights during an option period to extend through the end of phase 2 testing in the United States.

According to Medicis' executive vice president Mitchell S. Wortzman, Ph.D., even though the research is preliminary, the potential impact that a topical botulinum toxin product could have on the market is compelling.

"Conventional wisdom suggests that the botulinum toxin molecule is too large to penetrate the skin, but the preliminary data that Revance has produced certainly makes one sit up, and say these guys may be on to something," he says.

Dr. Wortzman is also Medicis' chief scientific officer.

"Time will tell if they can really deliver targeted doses in a therapeutic way, but it's interesting - it causes one to question conventional wisdom, and that's sometimes where the greatest breakthroughs come from," he says.

"Medicis' injectable botulinum toxin product Reloxin is expected to compete in the aesthetic market with Botox, but what Medicis doesn't have rights to on the injectable side is the therapeutic distinction," said Ken Trbovich, a stock analyst with RBC Research in Denver, Colo.

"The potential for Revance to have a therapeutic indication such as hyperhydrosis could, therefore, be a big advantage for Medicis."