Neurotoxin products poised to give Botox U.S. competition
Neurotoxins PurTox (Mentor Corp.), Xeomin (Merz Pharmaceutical), and, recently FDA-approved Dysport (Reloxin; Medicis), are all making their way to the U.S. market to give Allergan's Botox a run for its money. But, so far, one expert tells Cosmetic Surgery Times , few true standout attributes have emerged among the products to set any apart from the current gold standard.
The most extensively studied is Dysport, with phase III clinical trials performed on 2,300 patients and more than 4,800 treatments. The trials looked at factors including onset of action, the extent of action, or "diffusion" — the duration of the product's efficacy.
The rates of adverse events between Dysport and Botox were generally the same, as was diffusion, and the studies took into account the effects of multiple treatments and treatment cycles, Gary Monheit, M.D. tells
A QUESTION OF EFFICACY "The treatment cycles were looked at because one of the big worries concerned neutralizing antibodies — whether there are more or less of them and whether they will affect the efficacy of the drug as it is used repeatedly with people year after year," explains Dr. Monheit, associate clinical professor of the Departments of Dermatology and Ophthalmology at the University of Alabama, Birmingham, Ala. The trials looked at as many as five treatment cycles of Dysport and found no differences in efficacy or adverse events. In fact, the researchers found that adverse events seemed to diminish as the treatment cycles went on, Dr. Monheit says.
Interestingly, onset of action was one area in which there could be a difference, with Dysport appearing to take effect a little sooner than Botox, Dr. Monheit adds.
"Subjects were asked when they first noticed that the [Dysport] appeared to be working, and 50 percent said as early as day two and 70 percent said day three," he relates. "We've always thought the onset of action with Botox was more like about five to seven days, but those studies were never done for Botox and we really don't know for sure if that was an accurate assessment."
The duration of Dysport's efficacy appeared to be slightly shorter in men than in women, but a variable dose study comparing 60, 70 and 80 units in men with 50, 60 and 70 units in women showed that duration leveled out. "The response curve clearly had to do with individualizing the dosage to the patient's muscle mass," Dr. Monheit notes. The individualizing factor also may come into play with regard to treatment with Botox and other toxins.
CONVERSION RATE The basic conversion of rate 2.5 to 1 was used in studies conducted in the U.S. and Europe, but that rate simplified matters when more variables should be considered in the conversion, Dr. Monheit emphasizes. "Even though we would like to say we could make a one unit conversion to another, it is something that is difficult to do because the units are simply different. I think that rather than talk about the units, one has to understand what the details are of the ideal doses used by Ipsen in the...different sites that have been tested."
The bottom line for conversion, as well as the dose rate, may be to aim for an appropriate range based on factors including gender, muscle mass and the area of injection rather than a specific rate. "We've done this in clinical practice with Botox, but it's never really been studied statistically," Dr. Monheit says. "The key is that we shouldn't 'cookbook' our neurotoxin, whether it's Dysport or Botox. It should be individualized, and every patient during the exam should frown or move whatever muscles that will be injected so we can see what the muscle mass is and provide the correct dosage."
'NAKED' NEUROTOXIN The next neurotoxin to the U.S. market will likely be PurTox, which takes its name from the fact that, unlike Dysport and Botox, it is a 'naked' neurotoxin, without a hemagglutinin or non-hemagglutinin complex.
At a complete molecular weight of 150 kd, PurTox is the lightest neurotoxin, but since Dysport and Botox are both reduced to 150 kd upon injection, after the outer complex of the hemagglutinin or non-hemagglutinin breaks away, all appear to even out in the end.
"There were some concerns about the potential risk of lighter proteins versus heavier proteins and concerns that perhaps the lighter ones could travel further and possibly have more diffusion into areas you don't want," Dr. Monheit explains. "But if the true neurotoxin protein is only 150 kd, it will not move or diffuse any more ...than the others." Phase III studies on PurTox, in which 400 subjects were followed for six months, have been completed, and again, parameters of safety, efficacy, dosage and onset appeared to be basically the same as the other neurotoxins. Also in the pipeline is Xeomin, another uncomplex neurotoxin, without the outer complexes of protein. Studies on it have so far shown similar results for response, duration, efficacy, safety and onset.
With so much research behind all of the neurotoxins, the only remaining mystery behind the new generation will be which ones will rise to the top. "It's going to be interesting," says Dr. Monheit. "We'll probably have three new neurotoxins on the market within about five years, and all appear to work well. Right now we have a gold standard in the form of Botox, so it will be interesting to see which ones doctors choose."
Dr. Monheit is a consultant and clinical investigator for Allergan, Genzyme, Colbar/J&J and Ipsen/Medicis.