The Future of Toxins

The neuromodulator market is about to get crowded. The recent initial public offering of Evolus Inc is likely to be followed by approval of its product by the FDA.1 When this happens, according to public information, is likely to be the second half of 2018 (based on PDUFA date of May 15, 2018). The drug’s neurotoxin, known as DWP-4502 is a 900kDa botulinum toxin type A complex protein that, as the Evolus prospectus states, is the same size as Botox. 

This product has been used in several clinical trials in the United States, Canada, and the European Union. It met its primary endpoints for treatment of glabella rhytids. The company has stated that it plans to market the product only for cosmetic indications and that this should provide it with greater pricing and marketing flexibility. How this product differs from existing products will be determined when they release their data from clinical trials. It will be interesting to see how it compares with existing and newer formulations.

Revance Therapeutics Inc is also seeking approval of its type A toxin known as daxibotulinumtoxinA. This neurotoxin has been studied in the United States and Canada in several trials. Unlike other products, it uses a proprietary excipient to stabilize its toxin. The company is also seeking approval to treat glabella lines and has said that its toxin “has shown the potential of becoming the first long-lasting injectable formulation of botulinum toxin type A.”3 

This increase in duration would likely be welcomed by patients who could plan to spend less time visiting their doctors’ offices. Duration may prove to be a marketing advantage depending on the adverse event profile. Revance has stated that it will pursue therapeutic indications as well as its cosmetic ones. It is interesting to speculate on how this product achieves its stated increase in duration. If, as has been posited in the past, the botulinum toxin cleaves proteins responsible for release of acetylcholine and that sprouting of neurons is required to restore functionality, it will be interesting to see how this protein delays sprouting or whether a different mechanism is at work.

Revance had initially been focused on the delivery of topical toxins. However, this has not proven to be as efficacious as had been hoped. It is possible that variations in delivery will enable them to resume this indication. 

Improvement for All Toxins

The 3 toxins currently available—Botox, Dysport, and Xeomin—have a range of indications and the US market for toxins has grown in recent years. 

The products require different doses and their onset, duration, and diffusion appear to differ. However, each has found a niche in the aesthetic world. In order to expand their business and fend off competitors, it seems likely that newer indications will be pursued. At the same time, the companies may increase their advertising and promotions budgets. This could result in a net improvement for all toxins as more and more people begin to get treated. Pricing competition may also become a factor in use and, as has been done in the past, it is possible that one company could promote both to physicians and to patients and create demand that does not presently exist.

Given the size of the market, plenty of room exists for 5 products. It is likely that differences in onset, duration, price, and diffusion will help consumers and physicians sort out how they get used. 

beer

Dr Beer is in private practice in West Palm Beach, FL. He is also a volunteer clinical instructor in dermatology at the University of Miami, a consulting associate in the department of medicine at Duke University, and shareholder and director of the Cosmetic Bootcamp meeting. For information on upcoming Cosmetic Bootcamp Meetings, please visit www.cosmeticbootcamp.com. 

Disclosure: Dr Beer is an investigator for Evolus Inc, Revance Therapeutics Inc, Galderma, and Allergan and may or may not own shares of these companies at any given point in time. Dr Beer was an investigator and is a trainer for Kybella. He is an owner of Theraplex LLC, and consults, speaks, or performs clinical trials for Galderma, 3M, Sanofi Aventis, Bioform Medical, Allergan, and Stiefel, a GSK company.

References

1. Evolus, Inc. announces pricing of initial public offering of common stock [news release]. Irvine, CA: Evolus Inc; February 7, 2018. https://investors.evolus.com/news-releases/news-release-details/evolus-inc-announces-pricing-initial-public-offering-common. Accessed February 19, 2018.
2. Taylor, NP. Evolus plans $75M IPO to bring Botox biosimilar to market. Fierce Biotech. January 10, 2018.  https://www.fiercebiotech.com/biotech/evolus-plans-75m-ipo-to-bring-botox-biosimilar-to-market. Accessed February 19, 2018.
3. About Revance. Revance Therapeutics, Inc website. http://revance.com/company/index.php. Accessed February 19, 2018.