Update on the Neurotoxin Pipeline

Modern Aesthetics®: What is the current landscape for neurotoxins, and where do you see it going in approximately 1 to 2 years?

Joel Schlessinger, MD, FAAD: We have had such a wealth of innovation in neurotoxins over the past 6 to 10 years, and that has led us to have four useful and frequently used toxins at present, with three new ones on the horizon or in early rollout, that we will be integrating into clinical practice. The toxins that we currently have are botulinum toxin, one example’s being Botox Cosmetic (onabotulinumtoxinA) from AbbVie. We also have Dysport (abobotulinumtoxinA) from Galderma, Jeuveau (prabotulinumtoxinA-xvfs) from Evolus, and Xeomin (incobotulinumtoxinA) from Merz Pharma.

MA: Which are the new toxins on the horizon?

Dr. Schlessinger: The one coming up first is Daxxify (daxibotulinumtoxinA-lanm) from Revance. Then there are Botulax (letibotulinumtoxinA) from Hugel and relabotulinumtoxinA from Galderma.

MA: What is the FDA status of the upcoming products?

Dr. Schlessinger: Daxxify was FDA-approved in September 2022 for the temporary improvement in the appearance of moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity in adult patients. It is expected to be available commercially sometime in the next few months but is in early rollout at this time. News sources have stated that it’s a likely possibility that the Hugel product will be approved by the FDA sometime this year, assuming that it goes through approval with no interruptions, because a Biologics License Application for this product was submitted in October 2022. The new Galderma product is still in clinical trials.

MA: What are some of the major differences between these products?

Dr. Schlessinger: This is a remarkable time when we have toxins with unique differences, ranging from the longevity of the toxin to the constitution methods to the additives within the toxin. And, over time, with some luck, we will have toxins that are dispensed as liquids and with different potential longevities of their own. It’s an exciting time for toxins.

MA: Do you have any comments about the Galderma product in development?

Dr. Schlessinger: I have participated in the Galderma relabotulinumtoxinA trials, and it’s exciting that [the plan is to offer] this product … in a liquid preparation. It will certainly simplify the process significantly, and there will be quite a few individuals that will be happy to have the product more easily prepared and more standard of a reconstitution, because the process of reconstitution is always a challenge.

MA: What can you share about the upcoming Hugel Botulax product?

Dr. Schlessinger: I participated in that trial. It is currently under review in the United States and Australia and is already available in 28 countries worldwide, with recent approvals in Europe and Canada.

MA: How do you choose which toxin to use on a particular patient?

Dr. Schlessinger: There’s really not an exact science behind which toxin is used in which situation. However, I tend to favor the toxins such as Botox, Jeuveau, and Xeomin for my middle-aged to older patients who might have a tendency toward brow ptosis or eyelid-related issues because these toxins are generally kinder and gentler for these individuals. At this time, I use Dysport for my younger patients and those individuals who want a more significant effect of the toxin for their treatment. There are some patients who are younger who wish to have zero or no movement in their brows or upper forehead, and those individuals are probably going to tend to prefer a toxin such as Dysport or Daxxify.

MA: What are your concerns about ptosis?

Dr. Schlessinger: There’s always going to be some incidence of ptosis from these toxins, and that’s a normal and expected side effect of these products. The question, however, is whether that ptosis will last longer in these presumably longer-lasting products or not, and that remains to be seen. Additionally, brow ptosis is a very definite concern with Daxxify (and to some degree Dysport) if the patients aren’t properly chosen. In anyone who has that potential (low-lying eyelids or significant forehead wrinkles with elevated brows), I avoid the “stronger” toxins and steer them toward Botox, Jeuveau, or Xeomin.

MA: What is your clinical assessment of Daxxify?

Dr. Schlessinger: I participated in the clinical trials for Daxxify and can state there will be a learning curve for dermatologists because it does have a larger field of action and it’s much more powerful than some of the other toxins that we are used to using. I do worry about its use in the hands of less-skilled practitioners or in med spa situations as their lack of training may lead to prolonged adverse events.

MA: Is that because it lasts longer? That’s one of the benefits that are showing up in prerelease marketing, in that it needs to be injected less frequently because it lasts longer.

Dr. Schlessinger: That’s a very interesting point because the Daxxify FDA-approved package insert does not state that it is going to last longer than other toxins on the market. I am an author of an article that actually addresses this question,¹ but the key point here is that this is a study of only one product. In order to fully determine this, we will need to test it against the existing products in the proper dosage ranges. The package insert only says do not inject any more frequently than 90 days, which is also what all the current toxins state in their package inserts. Additionally, there have not been comparator trials that are referenced on the package insert that show however many approved units of Daxxify versus brand X of another toxin. Until we have those comparative trials, I’m somewhat reluctant to state that this is 100% more effective or longer lasting than other toxins, and, especially, I feel that it’s incumbent upon Revance to perform those trials, or other companies, for that matter, to compare those products before we de facto state that that is a real occurrence.

MA: What about the fact that Daxxify does not contain human or animal serum albumin like other similar products, so it’s vegan. Is that something you’d like to comment on?

Dr. Schlessinger: I think that’s a great distinction, and there are certainly some patients who will prefer to have a vegan product as opposed to a nonvegan product. In addition, there are some people that are allergic to albumin and, in particular, are allergic to eggs, so Daxxify will likely be helpful for them in that regard.

MA: The Daxxify marketing also states there is a unique trademarked peptide to stabilize it, allowing it to last longer, and it doesn’t need to be refrigerated. Is that something that’s of interest to talk about?

Dr. Schlessinger: Not having to be refrigerated is a nice option, as with Xeomin, but I will probably put it in a refrigerator just for safekeeping. Again, since I participated in the clinical trials, I am aware of this statement regarding the peptide, but the clinical trials did not address the mechanism of action for the peptide.

MA: Which toxins need to be reconstituted, and which don’t?

Dr. Schlessinger: All of them need to be reconstituted at present. Botox, botulinum toxin, comes as a crystalline powder in the bottom of a vial. In order to reconstitute it, you have to add saline to it, and that’s where the challenges occur, because if you add a small amount and claim to have X amount of units per [milliliter], it’s a lot different than if you dilute that out by two or three times and you have less than what you state is in each [milliliter] of fluid. That’s one reason why it would be nice to have a syringe that contains that product that does not need to be reconstituted.

MA: You are saying that none of the current products or those in development comes in a prefilled syringe?

Dr. Schlessinger: Correct. Many dermatologists would be happy to have a new toxin product that comes in a syringe so it is not able to be corrupted in any way, shape, or form. The new Galderma product will at least be fully reconstituted in a vial, ready to withdraw from the vial, but that doesn’t necessarily solve the issue.

1. Bertucci V, Solish N, Kaufman-Janette J, et al. DaxibotulinumtoxinA for Injection has a prolonged duration of response in the treatment of glabellar lines: pooled data from two multicenter, randomized, double-blind, placebo-controlled, phase 3 studies (SAKURA 1 and SAKURA 2). J Am Acad Dermatol. 2020;82(4):838-845.