A duo of experts from the pivotal, phase 3 ASPEN trial shared commentary on the impact of daxibotulinumtoxinA’s approval for adults with cervical dystonia.
Cervical dystonia has been traditionally treated with boluinumtoxin drugs, including Botox, Dysport, Xeomin, and Myobloc. The toolbox recently expanded with the FDA approval of Revance’s daxibotulinumtoxinA-Ianm (Daxxify), the first and only peptide-formulated long-lasting neuromodulator to treat the condition. DaxibotulinumtoxinA, a therapy previously approved for the temporary improvement of moderate to severe glabellar lines, received FDA greenlight based on results from the phase 3 ASPEN trial (NCT03608397) and its open-label study (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
Following the approval, ASPEN investigators Peter McAllister, MD, co-founder and medical director of the New England Institute for Neurology and Headache, and Atul Patel, MD, MHSA, medical director of the Kansas Institute of Research, provided thoughts on how this therapy will be used going forward. The duo shared insight on identifying optimal candidates for treatment, and questions on the agent’s use that will be answered in the coming years.
Atul Patel, MD, MHSA: The formulation of Daxxify includes a proprietary peptide. We can assume that the peptide has an impact on how well Daxxify binds to the receptors, and therefore can potentially provide a long-acting effect of the botulinum toxin for cervical dystonia patients.
Peter McAllister, MD: Mechanistically, Daxxify blocks acetylcholine release at the neuromuscular junction and thus relaxes the over-contracting neck muscles of CD patients.
Atul Patel, MD, MHSA: This provides another tool in our treatment toolbox and potentially allows for a longer acting botulinum toxin to be used in certain patients.
Atul Patel, MD, MHSA: Yes, certain patients are more appropriate for this treatment because of factors to do with their condition where their current treatment is not lasting for the full 12 weeks, the time point they can receive another treatment with current label indication and insurance coverage for the other botulinum toxins in the market. Also, Daxxify can be an appropriate treatment for patients who have barriers to access to care due to distance and time to get to clinic as well as financial reasons. Daxxify can potentially allow them to not have to come to clinic as often.
We want to ensure that individual providers are comfortable with the treatment. Revance is conducting an early experience and education program for certain providers to gain real world experience, following the PrevU program, we can then share this experience with other physicians who treat patients with cervical dystonia.
Peter McAllister, MD: In my opinion, Daxxify should be a first line therapy in any patient with CD, but it is particularly useful in patients who have had an inadequate response to prior neurotoxins, either because of lack of full efficacy, short duration of effect or tolerability issues.
Atul Patel, MD, MHSA: I think there will be a lot of questions on how Daxxify works in each patient, and in different groups of patients. We will be able to find out if there will be opportunities to treat the patient at different intervals and improve their response to treatment compared to current treatments.
Peter McAllister, MD: With increasing clinical use, we will get a better idea of the optimal dose of Daxxify for CD, and how long its duration is (ie time to retreatment) in the real world. We will also look at other therapeutic indications beyond CD.