A Novel Treatment for Botulinum Neurotoxin (BoNT) Adverse Effects

Botulinum neurotoxins (BoNTs), such as Botox®, Jeuveau®, Xeomin®, and Dysport®, are particularly versatile pharmaceutical agents with both aesthetic and therapeutic applications. While the extensive use of BoNTs in facial aesthetics is widely known, over 50% of the time, BoNTs are used to treat medical conditions such as muscle spasticity, chronic migraine, and overactive bladder.

BoNTs function by inhibiting the release of acetylcholine, a type of neurotransmitter, at the neuromuscular junction, rendering the targeted muscle nonfunctional. As a result, BoNTs are, in effect, a profound long-acting muscle-relaxing agent. Increasing doses of BoNT result in more intense, longer-lasting effects. Although most BoNT injections are accurately administered and accurately dosed, resulting in expected outcomes, BoNTs may be inappropriately administered or inaccurately dosed in both aesthetic and therapeutic settings, which may cause adverse events that are unacceptable to patients. Unfavorable aesthetic BoNT adverse events include heavy eyebrows secondary to excessive BoNT placed in the frontalis muscle and ptotic (droopy) eyelids when BoNT enters a nontargeted muscle. Unfavorable therapeutic BoNT adverse events include neck weakness, which may be secondary to inappropriate BoNT dose size and placement, and difficulty swallowing when BoNT enters a nontargeted muscle. Thankfully, most BoNT adverse events are mild and self-limited, and various regulatory agencies around the world, including the United States Food and Drug Administration (FDA), have attempted to minimize the impact of such adverse events via stringent regulations in the clinical use of BoNT. Nonetheless, depending on the indication, BoNT adverse events can affect many patients, which can find such adverse events uncomfortable, inconvenient, burdensome and impacting quality of life.

The current “solution” to many of the aforementioned adverse effects is to allow the BoNT to wear off, although alpha-adrenergic agonist eyedrops can sometimes temporarily elevate ptotic eyelids, an adverse effect that is sometimes associated with glabellar BoNT treatment.

More specifically, ReViVoxTM is a locally injected reversal agent that directly targets the inadvertently relaxed muscle by operating external to the neuron. The active pharmacological ingredient (API) of ReViVoxTM is a small molecule that, for decades, has safely and efficaciously been used in a systematic mode for applications in anesthesia and for treating myasthenia gravis, an autoimmune disease that is associated with muscle weakness.

The fact that ReViVoxTM functions external to the neuron distinguishes the drug from some other potential BoNT antidotes. Since ReViVoxTM operates this way, it can remedy all BoNT types. Additionally, unlike alternatives, ReViVoxTM would be administered if side effects are exhibited.

Beyond solving existing clinical challenges, DelNova’s solution, which is protected by a strong intellectual property portfolio, also expands the commercial market for BoNT. Currently, less than 10% of aesthetic candidates receive neurotoxin injections. BoNT may be heavily underutilized due to, among other reasons, potential patients’ concerns about adverse events. In addition, the advent of longer-acting neurotoxins, which reduce the frequency of injections, could naturally lead to longer-acting adverse events. Such adverse events could potentially be addressed with carefully designed and deployed remedies ReViVoxTM.

The clinical and commercial value of reversibility has strong precedent. A particularly interesting analogy is the evolution of hyaluronic acid (HA) dermal fillers. While initial generations of HA dermal fillers were short-lasting and irreversible, the most popular dermal filler currently is a long-lasting HA dermal filler, partly due to its reversibility – as needed – via the enzyme hyaluronidase. Similarly, ReViVoxTM enables broader and more creative clinical application of BoNT. Ultimately, ReViVoxTM reaffirms practitioners’ and patients’ confidence in the successful administration of BoNTs.