New forms of botulinum toxin type A emerge, compete for neurotoxin market

January 1, 2008

In the beginning, there was only Botox, but after years of owning the U.S. market with no competition, Allergan's brand of botulinum toxin will inevitably soon share the stage with several new neurotoxins that are working their way towards FDA approval.

Key Points

The leading future competitor for Botox will likely be Reloxin (Medicis), another botulinum toxin type A (BTX-A) that is already marketed in Europe under the name Dysport.

While data for Reloxin has been submitted to the FDA and a decision is expected soon, doctors struggle to find an accurate dosing comparison to Botox, and some trials have not reflected adequate comparison doses, says Joel Schlessinger, M.D., director of the Advanced Skin Research Center.

"There is almost no doubt that it's somewhat closer to 3 to 1," he says. "And the problem in comparing 2.5 units of Reloxin for every one unit of Botox is that there may be an inaccurate assumption that Reloxin doesn't work as well as Botox.

"The 3 to 1 conversion better reflects Reloxin's true activity and longevity," he says.

Packaging for Reloxin is expected to roughly correspond with a 100-unit vial of Botox, which should allow for easier reconstitution and conversion.

In addition to giving dermatologists an alternative to Botox, Reloxin may offer improvement in patients who are resistant to Botox. Dr. Schlessinger says, in his own experience in treating patients with Reloxin, he observes more diffusion than with Botox.

"I have found that with a given dose of Reloxin, there tends to be a little more of a coverage area; however, this may have to do with a variety of factors, including the vehicle, storage and how it was reconstituted, and may be a plus with this product," he says.

"It hasn't led to any increase in eyelid ptosis or eyelid problems in the trials. In fact, the data so far suggest a lower incidence of these problems with Reloxin than in the Botox trials," Dr. Schlessinger tells Dermatology Times.

Another interesting neurotoxin that could make its way to the United States is NT201, made by Merz Pharmaceuticals. The product is currently marketed in Germany for neuromuscular conditions, and approval for cosmetic indications is expected soon outside of the United States.

Unlike other new neurotoxins in the pipeline, NT201 is notable for lacking certain types of proteins to which some patients can develop antibodies leading to unresponsiveness.

"(NT201) uses what I call a 'leaner, meaner' molecule," Dr. Schlessinger says. "It has the 150 kilodalton subunit that isn't folded into a 900 kilodalton species, as is the case with Botox and Reloxin, but the question is whether this will afford it certain advantages and make it a more efficient form of botulinum toxin."

NT201 is expected to be tested soon to treat cervical dystonia and blepharospasm.

Mentor is currently in phase 3 trials on its version of BTX-A, called Puretox, and teams in China and South Korea are also working on forms of botulinum toxin.

Meanwhile, further out on the horizon is a concept in the very earliest stages of research that could turn the entire neurotoxin field on its ear - topical Botox.

It may sound like something right out of the back pages of a tabloid, but researchers in California have indeed found intriguing, albeit inconclusive results from the topical application of a BTX-A product for primary axillary hyperhidrosis.

"There's no clearly defined mechanism of action as to why this large a molecule is able to penetrate the dermis, but it should be very interesting to follow the research on this product and see where it goes," Dr. Schlessinger says.