Newly approved antiwrinkle drug challenges Botox’s dominance

A new antiwrinkle drug threatens Botox’s three-decade dominance of the facial injectables market.

The challenger is DaxibotulinumtoxinA-lanm or Daxxify, a neuromodulator protein that, like Botox, can temporarily smooth away frown lines between the eyebrows. The compound’s manufacturer, Revance Therapeutics, received a nod from the US Food and Drug Administration for the product in early September.

Daxxify’s major selling point is that its wrinkle-taming effects last longer than those of Botox and other rivals on the market. During clinical trials, patients injected with Daxxify showed reduced frown lines for a median of six months; some patients experienced changes for as long as nine months. Treatments on the market today usually persist for three to four months.

Daxxify “is the first one that has a difference,” says Lawrence Green, a clinical dermatologist at George Washington University School of Medicine. He was one of the contract investigators who ran clinical trials on Daxxify in the late 2010s. “The patients were really, really happy, because [the effects] lasted that long,” he adds.

The key ingredient in all of these wrinkle-reducing products is a tiny dose of a botulinum toxin. This group of proteins, derived from the bacterium Clostridium botulinum, freeze wrinkles by blocking nerve signaling to induce involuntary muscle relaxation. The toxin molecules are eventually metabolized, making the treatments temporary.

In other injectables, the botulinum toxin is stabilized with human serum albumin or animal proteins. Revance instead deploys a much more svelte stabilizer, a proprietary peptide consisting of only 35 amino acids to ferry the toxin to the neurons.

Botox was first approved in the US in 1989, and “all the other products that have come to market since then have essentially followed the same formula,” says Conor Gallagher, Revance’s vice president of medical affairs and scientific innovation. The company is the first to use a peptide stabilizer. “We have made a significant innovation in the Daxxify formulation,” he adds.

Gallagher says that Daxxify’s longer-lasting effects may result from higher levels of neurotoxin entering the neurons, thanks to the peptide formulation, though he emphasizes that this is still only a hypothesis. The stabilizer peptide is dotted with a high density of positive charges, so he suspects that it attracts the negatively charged toxin protein with enough positive charge to spare that it can still bind to negatively charged cellular nerve terminals. In contrast, human serum albumin does not carry any electric charge.

Given Daxxify’s success in reducing frown lines, Revance also plans to expand the product’s applications to treat muscle-control disorders that arise from damage to nerve pathways. The company has completed Phase 3 trials for the treatment of cervical dystonia, which is characterized by painful neck twitching, and Phase 2 trials for upper limb spasticity, in which the arms uncontrollably spasm. Botox has also been approved for use to treat these conditions.

Whether Daxxify ends Botox's reign likely boils down to the comparative price, says Green. Revance has declined to provide any information about its pricing strategy, though it says that Daxxify’s longer-lasting effects probably justify a slight premium in pricing.

For now, Green says his patients are excited about the imminent availability of Daxxify, especially at the prospect of reducing their clinic visits from three times a year to two times a year. “As much as they love me, they don’t want to see me that much,” he says.