FDA Approves Expanded Indication of DaxibotulinumtoxinA to Treat Cervical Dystonia

Mark J. Foley

The FDA has approved Revance’s daxibotulinumtoxinA-Ianm (Daxxify) for the treatment of cervical dystonia in adults, expanding its previous label as a therapy for the temporary improvement of moderate to severe glabellar lines. Powered by Peptide Exchange Technology, it becomes the first and only peptide-formulated, long-lasting neuromodulator for patients with cervical dystonia.¹

"We are very pleased to see the expansion of the Daxxify label to include our first therapeutic indication, unlocking a new market opportunity for Daxxify following the product’s recent launch in the aesthetics market. Further, we believe FDA approval represents a significant advancement in the treatment of cervical dystonia,” Mark J. Foley, the chief executive officer of Revance, said in a statement.¹ "Daxxify's differentiated efficacy, duration, and safety profile can help physicians deliver long-lasting symptom relief to patients suffering from cervical dystonia, while also helping payers address the total cost of care for this population."

The expanded indication was based on results from the phase 3 ASPEN trial (NCT03608397) and its open-label study (OLS; NCT03617367), which included 382 patients and 1240 treatments over an 88-week time span. 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).²

In the double-blind trial, which spanned 36 weeks, secondary end points, or 2-point improvement on Clinical Global Impression of Change and Patient Global Impression of Change at week 4 or 6, were both found to be consistent in the treated group and showed statistically significantly greater improvement over placebo (P <.001). Both dosed groups of daxibotulinumtoxinA were 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.

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"As an ASPEN investigator, I am excited to see the approval of a new treatment option to address symptom reemergence prior to retreatment, a common issue for cervical dystonia patients," Peter McAllister, MD, cofounder and medical director of the New England Institute for Neurology and Headache, said in a statement.¹ "Currently, patients experience painful and life-limiting symptom recurrence as early as 8 to 10 weeks in clinical practice but cannot be retreated until 12 weeks. Daxxify is the first long-acting neuromodulator that has the potential to address this significant unmet need—demonstrating durable symptom relief between treatment cycles and providing the opportunity to extend treatment intervals."

In the OLS, 357 individuals (271 from ASPEN-1, 86 enrolled de novo) received 985 daxibotulinumtoxinA treatments, with 87% of patients on at least 1 dose above 125 units. Mean TWSTRS total score averaged over weeks 4 and 6 improved from baseline in all treatment cycles; mean change from baseline increased with each cycle (cycle 1: mean change, –15.4; cycle 4: mean change, –19.9). Median duration (time to loss of ≥80% of peak treatment effect) ranged from 19.9 to 26.0 weeks in evaluable cycles. Symptoms continued to improve with successive with treatment doses up to 300 units, while AEs remained low.³

Foley added, "We look forward to conducting our early experience and education program, PrevU, which will involve a small group of thought leaders, followed by a progressive commercial rollout beginning in 2024. Today’s approval is an important milestone for Revance, marking the start [of] our therapeutics franchise."

REFERENCES
1. US FDA approves first therapeutic indication for Revance’s DAXXIFY (daxibotulinumtoxinA-Ianm) for injection for the treatment of cervical dystonia. August 14, 2023. Accessed August 15, 2023. https://investors.revance.com/news-releases/news-release-details/us-fda-approves-first-therapeutic-indication-revances-daxxifyr
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 August 15, 2023. https://investors.revance.com/news-releases/news-release-details/revance-reports-positive-results-aspen-1-phase-3-trial
3. Jankovic J, Comella C, Hauser R, et al. A phase 3 trial evaluating the efficacy, duration of effect, and safety of daxibotulinumtoxinA for injection in the treatment of cervical dystonia. Presented at: MDS Virtual Congress 2021. Abstract 100.