1. Four and Growing
There are four products currently FDA approved and available on the market: Botox Cosmetic (Allergan), Xeomin (Merz), Dysport (Galderma), and Jeuveau (Evolus). All four are approved for the glabella; Botox Cosmetic is also approved for forehead lines and crow’s feet.
2. Daxi is under review
Pivotal data have been published for daxibotulinumtoxinA (Revance) for glabella injection, and the fate of the new toxin is now in the hands of the FDA. It has a unique peptide that may be associated with less aggregation of the neurotoxin to itself and the bottle —seemingly leading to enhanced “duration” of cosmetic effect. Two double blind placebo controlled trials and an open-label study of ~2700 patients have demonstrated a median 24 weeks duration, versus 12 to 16 weeks observed in pivotal trials of current approved botulinum toxin products using similar endpoints (preservation of none/mild glabellar furrow at animation).
3. Talking duration
“Duration” is a surprisingly complex concept. When asked about duration, we need to indicate to patients that duration is based on very specific study endpoints. For some studies, duration is based on patients with severe or moderate animating glabellar furrows maintaining either a mild or no furrow. For other studies, duration is based on how long a 2-grade or a 1-grade improvement is maintained. And some studies look at a “return to baseline” duration. With any of these assessments, there is a “bell-shaped curve,” so some people will be on the lower end of the curve and some on the higher—which is why the “median” is really the best number to analyze.
There are four products currently FDA approved and available on the market: Botox Cosmetic (Allergan), Xeomin (Merz), Dysport (Galderma), and Jeuveau (Evolus). DaxibotulinumtoxinA (Revance) for glabella injection is under FDA review. “Duration” is a surprisingly complex concept that requires careful assessment.
4. Lasting effects
Neuromodulators don’t wear off overnight. There is a gradual waning of effect. Dose is a factor, as we know there is a dose-reponse curve. And while current toxin products at their FDA-approved glabellar dosing have shown pivotal trial efficacy for 12-16 weeks, response may actually vary—and some patients may return to the office at seven to eight weeks and be disappointed that they can now move their glabella. But, in these circumstances, the glabellar furrow movement is usually still a lot less than what was evident at baseline before treatment. Baseline photos can help document this for sure. And, it is important to explain to patients the notion of “waning of effect,” as efficacy falls from maximal efficacy to less efficacy. Recently, Galderma announced the results of their DREAM study—where patients were dosed on-label in the glabella with Dysport at six-month intervals for a year. Ninety-five percent of patients were satisfied with two treatments a year—even with a waning of effect by month five and six (consistent with Galderma Aspire patient loyalty program data that Dysport patients on average come in 1.9 times per year).
5. We Don’t Know How to Prolong Effects
Clinical trials often have a washout of about nine months—so there really should not be a cumulative effect of toxin evident in the trial results. Trials typically show that naive patients who participate in the study have a very similar response in efficacy and duration compared to non-naive patients. Patients often ask what they can do or take in order to try to prolong their botulinum toxin results. At this point, I don’t believe that there is any well-designed data to suggest that any vitamins or herbal remedies or even things like zinc supplementation makes neuromodulators last clinically longer. With zinc as well as other supplements, there are key factors to consider: 1.) How would zinc get into the nerve to work? 2.) Furthermore, are many people really zinc deficient in the first place—as we simply do not see cosmetic or dermatologic patients with cutaneous manifestations of zinc deficiency?
Relevant Disclosure: Dr. Cohen has served as both a clinical trial participant and consultant for Allergan, Galderma, Merz, Evolus, and Revance.