Neurotoxins on the Horizon: Bonti and Beyond

With at least three novel toxins—DWP-450 (Evolus), daxibotulinumtoxinA (Revance), and EB-001A (Bonti)—in development, core aesthetics physicians suspected that the treatment landscape was due to change. But when Allergan agreed to acquire Bonti for $195 million in September, it became clear that the market is hot, and high hopes are riding on the pipeline. EB-001A, currently in Phase 2 clinical trials, appears to have a rapid onset of action and short duration of effect relative to available toxins, suggesting potential new opportunities in the aesthetics realm.

Context

To be sure, the Allergan/Bonti headlines generated buzz, but a thoughtful pause is in order. While the acquisition indicates confidence in EB-001A, the agent is still in Phase 2 trials for two indications: reduction of scars post Mohs micrographic surgery and reduction of moderate to severe glabellar frown lines.

In a recent conversation, Mitchell Brin, MD, Chief Scientific Officer at Allergan, emphasized that, while excitement is understandable, there is still work to do before EB-001A reaches the market. Once the acquisition is complete, Allergan will play a role in planning and carrying out additional studies for EB-001A, including the Phase 3 pivotal trials.

The data thus far are intriguing. EB-001A is a form botulinum toxin type E—something aesthetic physicians have not yet had in our tool chest. It is characterized by a rapid onset of action of about 24 hours and a short duration of effect of roughly two to four weeks.

Like onabotulinumtoxinA (Botox), EB-001A binds the synaptic protein SNAP-25, though the two agents seem to interact with the protein in different ways, likely accounting for the difference in duration of effect. Dr. Brin notes that the light chain domains of the neurotoxin proteins seem to modulate duration of toxin effect.

“The data thus far are promising,” Dr. Brin says, “and there is a lot more we will learn about EB-001A as a result of our clinical work. We are very enthusiastic about the opportunity to further develop the product.”

Opportunity

In announcing its plan to acquire Bonti, Allergan pointed to data that suggest that up to 65 million Americans may be considering a facial injectable treatment. Yet nearly half of them say they are worried about an unnatural look. Data also show that roughly one-quarter of patients who receive Botox seek treatment just before an event.

For cosmetic dermatologists, these are important data points to consider both now with our existing treatments and in the future.

If EB-001A is FDA-approved, patients who are reluctant to undergo treatment due to concern about a possible unnatural result can be assured that the duration of effect is short and they will return to baseline quickly.

Indications are that Allergan may offer an incentive for patients who are injected with EB-001A to come back for Botox once the effects diminish. This follow-up marketing plan is brilliant, as it allows for a requisite period of time where the patient can see the benefits of neurotoxins and contemplate the quickly approaching end of this improved look, all with a coupon in hand.

In the meantime, we as expert physician injectors should focus on providing potential patients with high-quality before and after photos that demonstrate the natural, refreshed look we can achieve with neuromodulators, in contrast to some of the images we see on social media.

The rapid onset of action of EB-001A would be welcome for those patients who present for treatment just a day or two before a social event. Each of us in practice has had to disappoint procrastinating patients, informing them that available neurotoxins simply would not provide notable improvement in time for their event.

This also highlights an opportunity in our marketing and patient education to stress the importance—for now—of planning neurotoxin treatments around social events.

Finally, we already know that the judicious use of neurotoxins at surgical sites can relax muscles and reduce tension to support better wound healing with reduced risk for scarring. A quick-acting, short-duration neurotoxin would be especially desirable for use during the healing period.

Gateways

Some observers are already suggesting that EB-001 is like a gateway neurotoxin, allowing patients to “sample” the effects of injection at their leisure or even in the lead up to a social event and potentially facilitating a conversion to long-term use. It also may be useful to touch-up patients mid-cycle.

EB-001A is also a gateway to a new realm of neurotoxins outside the type A serotype. It will be interesting to see any other serotypes that may yet come into the space. Time will tell whether EB-001A ends up being a significant player in the market or a first blush exposure to the world of neurotoxins, but the potential addition of yet one more indication (Moh’s surgery) and an entirely new paradigm for treatment is exciting.

Finally, along with its investigational counterparts DWP-450 and daxibotulinumtoxinA, EB-001A may yet be a gateway for aesthetic physicians, opening new opportunities for patient care.