DaxibotulinumtoxinA Meets Primary End Point in Cervical Dystonia Study

Joseph Jankovic, MD

Revance Therapeutics announced that its investigational drug candidate for injection for the treatment of cervical dystonia, daxibotulinumtoxinA, met its primary end point in the phase 3 ASPEN-1 randomized, placebo-controlled, parallel group clinical trial.

In both the 125- or 250-unit dose groups of daxibotulinumtoxinA, the treatment met primary end point by demonstrating a clinically meaningful improvement in the signs and symptoms of cervical dystonia, on average, by weeks 4 through 6.

Both the 125- and 250-unit treatment groups showed a statistically significant greater change from baseline (12.7 and 10.9, respectively) compared with placebo (4.3; P <.001 and P = .0006, respectively) as measured on the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score. TWSTRS was used as a measure to evaluate features of the cervical dystonia condition, including severity, disability, and pain.

"I was delighted to see both the degree and duration of relief that daxibotulinumtoxinA for Injection provided trial subjects in ASPEN-1. Currently, most patients with cervical dystonia visit their physician 3 to 4 times a year for injections, which places a heavy burden on patients’ time and schedule. Often, the treatment effect wears off between injections, significantly impacting the quality of their work and personal lives,” trial investigator Joseph Jankovic, MD, professor of neurology, Distinguished Chair in Movement Disorders, and founder and director, The Parkinson’s Disease Center and Movement Disorders Clinic, Baylor College of Medicine, said in a statement.

The trial included 301 patients who were randomized 3:3:1 to receive a single treatmentof either 125 units or 250 units of daxibotulinumtoxinA for injection, or placebo for 36 weeks. Jankovic and colleagues documented that the median duration of effect from the agent was 24.0 and 20.3 weeks for the 125- and 250-unit groups, respectively, based on the median time to loss of 80% of the peak treatment effect.

WATCH MORE: Kristina Simonyan, MD, PhD, DrMed: Using Machine Learning to Diagnose Dystonia

Secondary end points that included a 2-point improvement based on Clinical Global Impression of Change (CGIC) and Patient Global Impression of Change (PGIC) at Week 4 or 6 were both found to be consistent among the clinician and patient results, as well as showed a statistically significant improvement greater than placebo (P <.001).

Both dosed groups of daxibotulinumtoxinA were found to be generally safe and well-tolerated through Week 36, with no recorded serious treatment-related adverse events (AEs) and no dose-dependent increase in AEs as well.

The incidence of dysphagia for the low- and high-dose groups (1.6%; 3.9%) and muscle weakness (4.7%; 2.3%), often considered AEs of botulinum toxin treatments for cervical dystonia, were “encouragingly” low in both groups, respectively, according to the investigators.

Aside from 1 case of neck pain reported as severe, all other treatment-related AEs were generally transient and mild to moderate in severity. Injection site pain (7.9%; 4.7%), headache (4.7%; 4.7%), and injection site erythema (4.7%; 2.3%) were the 3 most common treatment-related AEs for the 125- and 250-unit groups, respectively.

"If a treatment could offer longer duration of effect, thus requiring fewer trips each year for reinjection, I imagine patients would find this quite beneficial,” Jankovic added.

Revance noted that they expect results from ASPEN-OLS, the companion phase 3, open-label, long-term safety trial, which enrolled 354 subjects, in 2021. In that study, patients will receive up to 4 sequential treatment cycles of daxibotulinumtoxinA over the 52-week observation period and will be assessed on safety and immunogenicity. DaxibotulinumtoxinA for injection previously received orphan drug designation from the FDA in 2017 to treat cervical dystonia.

The investigational agent has also been observed in other clinical trials, including for the treatment of upper limb spasticity in patients who are post-stroke. NeurologyLive recently caught up with Peter McAllister, MD, medical director, New England Institute for Neurology and Headache, and chief medical officer, New England Institute for Clinical Research, who is among the lead investigators of the JUNIPER phase 2 trial that will look at daxibotulinumtoxinA for injection for the treatment of upper limb spasticity in adults after stroke or traumatic brain injury.

McAllister touted the JUNIPER phase 2 trial as, “the biggest new advance in neuro toxin research in the last 2 decades,” and backed the notion that post-stroke awareness has lacked in recent years.

Click here to read the full conversation.

REFERENCE

Revance reports positive results from ASPEN-1 phase 3 trial of daxibotulinumtoxinA for injection in cervical dystonia. News release. Revance Therapeutics. October 14, 2020. Accessed October 19, 2020. https://investors.revance.com/news-releases/news-release-details/revance-reports-positive-results-aspen-1-phase-3-trial​