The field of injectable neurotoxins is poised for growth. DaxibotulinumtoxinA or RT002 injection from Revance is likely to be submitted to FDA soon. The latest data for the agent, which incorporates proprietary peptide technology, show a sustained duration of effect that may differentiate from currently available neurotoxins. Jeffrey Dover, MD, co-director of SkinCare Physicians of Chestnut Hill, Associate Professor of Clinical Dermatology at Yale University School of Medicine, and Associate Professor of Dermatology at Brown Medical School, spoke with Modern Aesthetics® magazine about the data and the evolving neurotoxins field.
What do we know about RT002 based on the SAKURA study?
Jeffrey Dover, MD: RT002 performed remarkably well and consistently in the three SAKURA trials involving almost 2,800 individuals. The first two were control blinded trials of single treatments of glabellar lines, and the third was a long-term open label trial where subjects received as many as three sequential treatments for glabellar creases. Each of the studies showed not only that the effect of RT002 on glabellar lines was impressive but also of long duration. A positive result was considered a two-grade improvement from severe to mild glabellar lines or from moderate to no glabellar lines. The percentage of individuals who showed a 2-grade improvement was greater than we have seen with any of the other neuromodulators studied in this manner. Moreover, the median duration of effect was more than six months, compared to the conventional neuromodulator effect, which is about four months.
MORE TOXINS IN THE NEWS
DWP-450 (prabotulinumtoxinA, Evolus) received approval last summer from Health Canada for the temporary improvement in the appearance of moderate to severe glabellar lines in adult patients under 65 years of age. A BLA for DWP-450 is under review with the FDA.
EB-001A (Bonti) is transitioning to Allergan as part of a $195 million acquisition. Currently in Phase 2 clinical trials, EB-001A appears to have a rapid onset of action and short duration of effect relative to available toxins.
The fact that the effect of RT002 lasted an average of six months—a full 50 percent longer than what we see with all other neuromodulators—will have a significant impact on aesthetic medicine. The neuromodulators presently approved for use in the US last on average four months. Patients will now have a choice to make. They can opt to sticking with the gold standard toxins we have used for years, which give very nice results that last about four months, or the choice of an innovative treatment that is very safe, highly effective and lasts 50 percent longer, or about six months. The ability to have a treatment twice a year instead of three times a year will be highly desirable for many of our patients.
What stands out to you from the SAKURA trial data?
Dr. Dover: Three things stood out from the SAKURA 3 trial: safety, efficacy, and long duration.
Side effects were mild and insignificant; exactly as we would expect with any type A botulinum toxin.
RT002 is highly effective. The peak effects started about
10 days after injection. The percentage of subjects with a 2-grade difference was greater over four months than we have seen with any other neuromodulators tested in this manner.
Perhaps most striking was the duration of effect that approached six to seven months, compared with the typical effect of neuromodulators, which is around four months.
What do we know about RT002 and why it may have such a durable effect?
Dr. Dover: RT002 is a type A neuromodulator with unique characteristics that appear to account for the significant aesthetic effect and long duration. RT002 is the only neuromodulator using a proprietary stabilizing excipient peptide technology in its formulation, which may explain the high efficacy, long duration and a two-year product stability requiring no refrigeration.
PRP INJECTIONS: BUILDING A FOUNDATION OF DATA
WITH MURAD ALAM, MD
PIatelet-rich plasma (PRP) is among the hottest cosmetic procedures, but despite enthusiasm among the public and providers there hasn't been much research into its efficacy—until know. Murad Alam, MD, vice chair and professor of dermatology at Northwestern University Feinberg School of Medicine and a Northwestern Medicine in Chicago, recently spoke to our sister publication, Practical Dermatology® about his study on PRP for improving skin color and texture. Here's what he said about his findlings, which appear in JAMA Dermatology.
WHY IS THIS TOPIC IMPORTANT?
Dr. Alam: This topic is important to study because PRP is becoming an increasingly popular treatment for facial rejuvenation, but there is very little scientific evidence to show that it works, or what specific benefits it provides to patients. The treatment is attractive since it is natural, in that it uses a patient's own blood; it is minimally invasive, in that it doesn't require surgery; and it is relatively quick, and without much downtime. As scientists, however, we want to know whether it is actually effective at improving skin color or texture.
DESCRIBE YOUR RESEARCH AND FINDINGS.
Dr. Alam: We enrolled 19 participants in our study. Each received injections of PRP to one side of their face, and of saline to the other side. Six months later, patients noted that the side with PRP was smoother, with less roughness and fine wrinkles. Dermatologist raters looking at photographs did not notice a difference between the two sides.
This suggests that PRP may improve skin texture by a small amount after one treatment. It may have been easier for patients, who knew their faces well, to notice a small but real improvement. Dermatologist raters, who had to rely on photographs, may have been unable to see the change in texture, which does not always photograph well.
WHAT IS THE NEXT STEP?
Dr. Alam: The next step would be to perform additional studies to better understand the effectiveness of PRP for various treatments. We plan to study the changes in the skin after several treatments of topical PRP combined with microneedling. We also want to learn how long the results of PRP may last. Finally, it would be interesting to see if future studies showed PRP to improve skin color and complexion, which our initial study did not.
Can you give an overview of the toxin market currently? As an aesthetic physician, what do you see as the opportunity in this space?
Dr. Dover: New neuromodulators have been approved and are about to be approved by the US FDA. And while there are differences amongst these other toxins, they all perform quite similarly with good effects that last about four months. The holy grail for neuromodulators is longer duration without sacrificing safety. While increasing the dose of other toxins appears to increase the duration of effect by about a month, these outcomes do not approach the increased duration of effect of RT002, which has shown to be effective and safe in clinical trials.
As the neuromodulator market grows, all approved products should do well. And while the traditional neuromodulators with about four months of effect will continue to do well, a certain percentage of our patients will surely wish for a longer acting safe and effective neuromodulator. RT002 may become a premium product, but there is no doubt in my mind that a significant percentage of our patients will desire this benefit.