Unlocking the Latest in Toxins: A Discussion of Market Trends and FDA Breakthroughs With Dr. Joely Kaufman

Dr. Joely Kaufman’s recent YoungMD Connect workshop, “Unlocking the Latest in Toxins,” delved into market trends and US Food and Drug Administration (FDA) breakthroughs involving neuromodulator use in dermatology. She discussed new botulinum toxin A products, ready-to-use botulinum toxin, botulinum toxin E, and reversal agents. There was also discussion of adverse events and future frontiers with topical neuromodulators. Following is a summary of key takeaways from the session.

Daxibotulinum toxin A can be stored at room temperature like incobotulinum toxin A, which is helpful for concern of power outages. There are no accessory proteins in daxibotulinum toxin A and incobotulinum. Because daxibotilinum toxin A is formulated with stabilizing peptide excipient, this may increase the neurotoxin’s affinity for cell membranes. It is a 1:2 formulation with onabotulinum toxin A and its median duration of action is 6 months.

Letibotulinum toxin A is currently available in 28 countries. It was introduced in South Korea, where it is the country’s No. 1 toxin. This neuromodulator was approved by the FDA earlier this year, however, it is not yet available in the United States.

Ready-to-use botulinum toxin is a new product coming to the market. Concern for reconstitution errors has driven development. For this reason, it may be a good option for busy clinics. Relabotilinum toxin A and nivobotulinum toxin A are ready-to-use products free of complexing protein. These products are not yet FDA-approved or available in the United States. Neither product is a 1:1 formulation with onabotulinum toxin A.

Botulinum toxin E is the first non-A toxin that will soon be available in the aesthetic market and is notable for its fast onset and short duration. Trenibotulinum toxin E is a novel, short-acting neuromodulator that patients feel working within 24 hours. This was originally intended for patients who are new to botulinum toxins and want to temporarily trial its cosmetic effect. Botulinum toxin E can also help with post-operative pain, post-trauma, wound healing post-surgery, or acne and rosacea.

Reversal agents are not yet available for botulinum toxin. Many doctors would like to have a product that could act as an “eraser,” akin to how hyaluronidase acts to dissolve hyaluronic acid filler. The goal of a botulinum toxin reversal agent would be to increase acetylcholine in the motor end plate. An anti-acetylcholinesterase product is currently in development for reversal of neuromuscular blockage. It is unknown how long this effect could last or if it would be clinically meaningful.

Adverse events from aesthetic neuromodulators include headache, eyelid ptosis, and neutralizing antibodies. Temporary headache is the most common adverse effect of neurotoxins but has a similar rate to placebo and could be due to the act of injection itself. Eyelid ptosis occurs in less than 2% of patients in clinical neurotoxin trials. Neutralizing antibodies to neurotoxin is extremely rare and is mostly seen in neurology with very large doses. Patients who appear to not be responding to neuromodulators may instead be recruiting muscles. It is not true that the body is less likely to make antibodies to neurotoxin without complexing protein; if that were true, then neutralizing would be an option that could work. However, if patients wait for more than a year to have neurotoxin injected, this may help.

A possible future frontier in aesthetic toxin is topical formulations. A topical product was studied by Revance but did not perform well in Phase II trials. Because botulinum toxin is known to have anti-inflammatory effects—for example, decreasing TGF-beta— it is possible that topical formulations could help treat rosacea and other inflammatory skin conditions.