FDA Accepts sBLA for Revance’s Cervical Dystonia Treatment DaxibotulinumtoxinA


DaxibotulinumtoxinA, the first and only peptide formulated neuromodulator, has been shown to be safe and well tolerated in doses of 125 and 250 units, with clinically meaningful effect observed by both patients and clinicians.

Peter McAllister, MD, medical director, New England Institute for Neurology and Headache

Peter McAllister, MD

After showing positive results in a phase 3 clinical program, the FDA has accepted Revance Therapeutic’s supplemental new biologics license application (sBLA) for daxibotulinumtoxinA injection (Daxxify), as a new treatment for adults with cervical dystonia. The agency scheduled August 19, 2023, as the PDUFA date for the therapy.1

DaxibotulinumtoxinA is an acetylcholine release inhibitor and neuromuscular blocking agent indicated for the temporary improvement of moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity in adults. To date, the therapy has shown promising results in 2 phase 3 studies of cervical dystonia, ASPEN-1 (NCT03608397) and ASPEN-OLS (NCT03617367).

"Painful symptom re-emergence is very common for patients with cervical dystonia and up until now physicians have not been able to fully address this issue with existing treatment options," Peter McAllister, MD, medical director, New England Institute for Neurology and Headache, said in a statement.1 "As an ASPEN investigator, I am excited about the results of the DAXXIFY Phase 3 trials, which demonstrate that a long-acting botulinum toxin can help address this significant unmet need in the treatment of cervical dystonia."

In ASPEN-1, both the 125- and 250-unit dose groups of daxibotulinumtoxinA met the primary end point of clinically meaningful improvement in the signs and symptoms of cervical dystonia, on average, by weeks 4 and 6. In this randomized, placebo-controlled, parallel group study, the 125- and 250-unit treatment groups showed improvements of 12.7 and 10.9 points, respectively, on Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) vs the placebo group, which recorded changes of 4.3 (P <.001 and P = .0006, respectively). TWSTRS was used as a measure to evaluate features of the cervical dystonia condition, including severity, disability, and pain.2

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The trial included 301 patients randomly assigned 3:3:1 to receive a single treatment of either 125 units or 250 units of daxibotulinumtoxinA for injection, or placebo, for 36 weeks. The median duration of effect from the agent was 24.0 and 20.3 weeks, respectively, based on the median time to loss of 80% of the peak treatment effect. Secondary end points, or 2-point improvement on Clinical Global Impression for Change and Patient Global Impression of Change 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.

"Positive results from our ASPEN Phase 3 clinical program demonstrate the potential of DAXXIFY® to bring sustained symptom relief to cervical dystonia patients, along with the potential for reduced frequency of annual injections,” Mark J. Foley, chief executive officer, Revance, said in a statement. “With the FDA’s acceptance of our sBLA and our upcoming PDUFA date in August 2023, we are one step closer to setting a new standard of care for cervical dystonia patients, where botulinum toxins are considered a first line treatment."1

1. Revance announces US FDA acceptance of supplemental biologics license application (sBLA) for Daxxify (DaxibotulinumtoxinA-Ianm) for injection for the treatment of cervical dystonia. News release. January 6, 2023. Accessed January 10, 2023. https://investors.revance.com/news-releases/news-release-details/revance-announces-us-fda-acceptance-supplemental-biologics
2. 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 January 10, 2023. https://investors.revance.com/news-releases/news-release-details/revance-reports-positive-results-aspen-1-phase-3-trial
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