Modulating Expression

Physicians share their techniques for obtaining better longevity and more natural-looking results with botulinum toxins.
Improving longevity and outcomes with neurotoxins

What started as a simple injection to lessen crow’s feet has blossomed into a multibillion dollar market and given rise to today’s medical aesthetics industry. With nearly 30 years of experience and a growing variety of botulinum toxins entering the market, the current focus in neuromodulation is on extending the longevity of results and delivering natural-looking outcomes.

In addition to the three currently available neuromodulators—Botox Cosmetic (Allergan), Dysport (Galderma) and Xeomin (Merz Aesthetics)—there are four more botulinum toxin type A (BtxA) products currently in Phase 2 and Phase 3 clinical trials. They include an injectable from Croma in Austria; Revance Therapeutics RT002; Evolus from Korea-based Daewoong Pharmaceuticals, which will be distributed in the U.S. by Alphaeon; and a new liquid toxin from Galderma. “This is one that I am looking forward to because it will be a premixed toxin,” says Anthony J. Wilson, MD, a dermatologist with Richard L. Zeff, MD, PA, in Stratham, New Hampshire. “This could be very nice for practitioners because diluting the products takes time, and there is inconsistency and human error in mixing.”

For several years, Revance Therapeutics has been simultaneously working on two BtxAs: RT001, a topical formulation, and injectable RT002. After RT001 failed to reach its primary endpoints in Phase 3 trials, the company shifted its focus to RT002 as it reevaluates its topical program. “We are going back to our preclinical program with RT001 to understand what we can do better,” says Abhay Joshi, chief operating officer at Revance. “Once we have a more complete understanding from the clinical data, we will come back and hopefully jumpstart the program down the road.”

RT001 and RT002’s differentiating characteristic is the use of a proprietary peptide called TransMTS, which Revance believes will offer better longevity. “TransMTS is used in combination with our highly purified neurotoxin,” says Joshi. “It creates a complex ionic interaction between the toxin and the peptide that allows the product to be more stable and possibly impart increased duration.”

Results of the company’s Phase 2 data is promising, notes Chicago-based plastic surgeon Steven Dayan, MD. “In the Belmont trials, it was a one-point improvement that showed a significantly longer duration, so the data is not yet conclusive but it is exciting,” he says. “They are using a 40-unit dose to achieve that longer duration of four to six months. But is that 40-unit dose equivalent to 20 units of Botox? It’s hard to say.”

Dr. Dayan posits that if Revance is able to achieve better longevity of results, other companies may respond with higher dose trials in an effort to meet the same duration of effect. In fact, this is already happening.

Increasing Longevity

John H. Joseph, MD, director of The Clinical Testing Center of Beverly Hills in California, published “Does Increasing the Dose of AbobotulinumtoxinA Impact the Duration of Effectiveness for the Treatment of Moderate to Severe Glabbelar Lines?” in the Journal of Drugs in Dermatology (JDD) last December. He initiated the study based on his experience working with Dysport during its clinical trials.

“In one particular trial, we were allowed to vary the dose based on the muscle mass,” he says. “When we crunched the data, it clearly showed that as we increased the dose, duration also increased, and it was linear—it didn’t plateau.”

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