Topical Botulinum Toxin is Coming!

Botulinum toxin first came into clinical use in the early 1990s. Since then it has become very widely used, and is a billion dollar business. It acts by blocking the transmission of the signal from the nerve to the muscle, so the muscle is not stimulated and does not contract. Fortunately, the product is specific for the motor nerves and it does not affect the sensory nerves. Thus there is no localized loss of sensation or numbness associated with the use of botulinum toxin.

From the onset, the product has been injected into the target muscles. The toxin molecule is large, and it is difficult to get large molecules through the skin intact. Furthermore, in many areas the product must be placed precisely, so as not to affect muscles that would give an undesireable effect. Droopy upper lids or an assymetrical smile are examples of unwanted botulinum toxin effects.

Topical Botulinum Toxin?

Revance Therapeutics, a start up company, has been working to develop a topical form of botulinum toxin. This would be an advantage for people who are adverse to needles. Botulinum toxin is a relatively large molecule, and conventional wisdom would suggest that it would be difficult or impossible to get such a large molecule through intact skin. The molecule would have to be in good enough shape to be functional.

Apparently Revance has overcome this obstacle and it is working on getting approval for its product for at least 2 different applications. The first of these is for the treatment of the wrinkles by the corner of the eyes, the "crow's feet". If the product is going to work at all, this should be a prime location. The skin in this area is thin, and the placement of the toxin does not have to be very exact. The product will be applied in the physician's office and the patient will have to wait while it is occluded for 20 minutes. How it will compare in price to the injectable toxin is unknown.

Botulinum Toxin Wars

Now that Dysport, which was going to be named Reloxin, has been approved by the FDA, you can expect to see extensive advertising by Allergan (Botox) and Medicis (Dysport) implying that theirs is the better product. Dysport has been used for years in Europe and Canada, and the differences between the products are less than the differences between fillers. Although they both have Botulinum Toxin A as their active ingredient, they are manufactured differently and there are some differences in their makeup and action.

Botulinum Toxin Alert: New Labeling for Botox and Others

The FDA has recently released additions to the labeling requirements for all Botulinum Type A Products. These actions are a result of adverse events that have occurred in both approved and unapproved uses where the toxin has spread beyond the injection site causing symptoms of botulism (difficulty breathing, difficulty swallowing, muscular weakness, drooping eyelids, constipation, aspiration pneumonia, speech disorder, facial drooping, double vision, or respiratory depression). The postmarketing case reports of these adverse events occurred primarily in children being treated for muscle spasticity due to cerebral palsy, and in adults being treated for spasticity or cervical dystonia.
It is important to note that, according to the FDA, “Definitive serious adverse event reports of distant spread of toxin effect associated with dermatologic use of Botox at the labeled dose... have NOT been identified."

The FDA also has informed the manufacturers that development of a Risk  Evaluation and Mitigation System is necessary. The System would include a Communication Plan to provide more information regarding the risk for distant spread of botulinum toxin effects after local injection, as well as information to explain that botulinum toxin products cannot be interchanged. The System also would include a Medication Guide that explains the risks to patients. Once it is developed, dermatologists will distribute the Medication Guide to patients at the time of injection.

The bottom line is that this is an administrative change, but it does not indicate that there is any new information or that there has been any change in the previously understood potential side effects of Botulinum A Toxin. It is likely that the release of these guidelines will hasten the approval of Reloxin, one of several new Botulinum A Toxins in the pipeline, and the one that is closest to release. The appearance of competitors to Botox will almost certainly bring lower prices to consumers.

Gerald N. Bock MD

California Skin & Laser Center

Stockton & Lodi, CA

Reloxin: When?

The FDA had previously delayed the release of Reloxin, a Botox analog, because of administrative issues. Medicis, the US company that will be distributing Reloxin, had filed additional paperwork with the FDA detailing its plan for follow up of adverse events. The FDA was supposed to give Medicis an answer this month, but there has been no announcement forthcoming. The reasons are unclear, at this point.

Reloxin Approval Put Off Again

Approval for Reloxin, a competitor for Botox, appears to have been delayed again. Reloxin, like Botox, is Botulinum Type A. It is to be marketed by Medicis, now part of Johnson & Johnson, while Botox is manufactured by Allergan. Reloxin was supposed to be approved in the summer or fall of last year, but the FDA rejected the application because they felt that Medicis had not developed sufficient plans to follow up potential side effects. The new approval date was to be this month, but the FDA has now extended the approval period until April 13.

Botox and First-Impressions

Making a better first impression is an important asset for people who interact with others for a living. A recent study suggests that treatment with Botox may increase your odds of making a favorable impression.

Botox for Biden?

A recent article in the New York Post suggests that Joe Biden may have had Botox treatment before the recent vice presidential debates. The article shows before and after photos which, despite the vehement denials of Biden's staff, clearly shows the effects of Botox, provided that the photos have not been doctored. The residual movement of the lateral eyebrows is typical of well done Botox. This allows for some forehead expression as compared to the "plastic forehead" that was typical of Botox placement when the product first was released. Of course, there are some patients who like the "plastic" look, and they remind me "Renember, I'm the one who doesn't want to move her forehead."

Botox for Shrinking Pores and Reducing Oiliness

In the current issue of the Journal of Drugs in Dermatology there is a preliminary report of the use of Botox to reduce facial pore size and oiliness. The paper presents photos of skin that apparently has smaller pores and appears smoother. The reduction of oiliness was based on the patient's impressions. The report only covered the results after one month, so there is no indication of how long the results, if real, might last.

Botox for Headaches

Botox has been used to treat migraine headaches for a number of years. This began following initial anecdotal reports of migraine improvement in people who were receiving Botox for other purposes. However, there have not been good controlled studies to demonstrate the effectiveness of this treatment.