FDA-Approved Injection DaxibotulinumtoxinA Shows Efficacy for Cervical Dystonia Treatment in Phase 3 ASPEN-1 Trial

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Revance’s daxibotulinumtoxinA-Ianm (Daxxify) is the first and only approved peptide-formulated, long-lasting neuromodulator for patients with cervical dystonia.

Atul Patel, MD, MHSA, physiatrist and vice president at Kansas City Bone & Joint Clinic

Atul Patel, MD, MHSA

Credit: Kansas City Bone & Joint Clinic

In recent news, Revance announced the publication offindings in Neurology from the pivotal phase 3 ASPEN-1 trial (NCT03608397) assessing daxibotulinumtoxinA-Ianm (Daxxify), an FDA-approved treatment for cervical dystonia.1,2 All told, these results provided evidence that Daxxify reduces dystonia more effectively than placebo in adults with moderate-to-severe idiopathic cervical dystonia.3

The approval of the expanded indication in August 2023 was based on results from ASPEN-1 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. Additionally, 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).3

Top Clinical Takeaways

  • Daxxify, an FDA-approved treatment, demonstrated superior efficacy over placebo in reducing cervical dystonia symptoms in adults.
  • Results from both the ASPEN-1 trial and its open-label study indicate sustained improvement with successive treatments and a favorable safety profile for Daxxify.
  • The expanded indication for Daxxify offers a promising advancement in cervical dystonia treatment, potentially reducing symptom reoccurrence between injections.

“As an investigator in all stages of the ASPEN program and a participating physician in the Daxxify cervical dystonia PrevU program, I’m happy to see publication of the pivotal study results in a peer-reviewed journal for the neurology community,” coauthor Atul Patel, MD, MHSA, physiatrist and vice president at Kansas City Bone & Joint Clinic, said in a statement.1 “Importantly, the real-world clinical results of Daxxify from the patients I have injected so far in PrevU, including safety, efficacy and duration, are in-line with those seen in the ASPEN-1 study. By offering a long duration of treatment effect, Daxxify can help reduce symptom reoccurrence between injections, which is experienced by most patients being treated with conventional botulinum toxins. This would represent a significant advancement in the treatment of cervical dystonia, something we have not seen in decades.”

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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, showing 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.

Investigators noted that treatment-related treatment-emergent AEs (TEAEs) were experienced by 29.6% of patients treated with the 125-unit, 23.8% with the 250-unit, and 17.4% with placebo, with injection site pain reported as the most common one overall. Authors also noted that the most frequent reported treatment-related TEAEs of interest were muscular weakness (4.8%, 2.3%, 0%), musculoskeletal pain (2.4%, 3.1%, 0%), and dysphagia (1.6%, 3.8%, 0%) in the 125-unit, the 250 unit, and placebo, respectively.

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.4

The company also announced that the Centers for Medicare & Medicaid Services assigned a permanent J-code (J0589), intended to simplify reimbursement for providers and expand access for patients, for Daxxify in patients with cervical dystonia.“We are very pleased to receive our permanent J-Code for Daxxify as we continue to make great progress with our cervical dystonia PrevU program and prepare for launch,” Mark J. Foley, chief executive officer, said in a statement.1 “Thanks to the hard work of our therapeutics team, we have received our reimbursement code, secured coverage for over 100 million commercial lives from top payers across the country and are on track to commercialize Daxxify in the therapeutics market mid-year.”

“Further, our confidence in Daxxify’s ability to deliver a favorable duration and safety profile in real-world cervical dystonia patients continues to grow based on positive feedback from our PrevU physicians and the over 250 patients that have been treated to date in the PrevU program,” Foley continued in a statement.1 “Based on Daxxify’s unique clinical profile, our early clinical experience and advances in our reimbursement and coverage efforts, we look forward to providing patients suffering from cervical dystonia with a compelling alternative to their conventional treatment options.”

REFERENCES
1. Revance Receives Permanent J-Code for DAXXIFY® and Announces Publication of DAXXIFY Pivotal Study (ASPEN-1) Results in Neurology®. News Release. Revance. Published February 2, 2024. Accessed March 15, 2024. https://investors.revance.com/investors/Press-Releases/news-details/2024/Revance-Receives-Permanent-J-Code-for-DAXXIFY-and-Announces-Publication-of-DAXXIFY-Pivotal-Study-ASPEN-1-Results-in-Neurology/default.aspx
2. Comella CL, Jankovic J, Hauser RA, et al. Efficacy and Safety of DaxibotulinumtoxinA for Injection in Cervical Dystonia: ASPEN-1 Phase 3 Randomized Controlled Trial. Neurology. 2024;102(4):e208091. doi:10.1212/WNL.0000000000208091
3. US FDA approves first therapeutic indication for Revance’s DAXXIFY (daxibotulinumtoxinA-Ianm) for injection for the treatment of cervical dystonia. August 14, 2023. Accessed March 15, 2024. https://investors.revance.com/news-releases/news-release-details/us-fda-approves-first-therapeutic-indication-revances-daxxifyr
4. 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 March 15, 2024. https://investors.revance.com/news-releases/news-release-details/revance-reports-positive-results-aspen-1-phase-3-trial
5. 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.
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