A Phase IV, Randomized, Double-Blind, Crossover Study to Compare the Clinical Safety and Efficacy of AbobotulinumtoxinA and OnabotulinumtoxinA in Adult Upper Limb Spasticity.

INTRODUCTION

Lack of head-to-head comparative safety and efficacy data for abobotulinumtoxinA (aboBoNT-A) and onabotulinumtoxinA (onaBoNT-A) represented an important gap for informed spasticity management. This study compared the safety and efficacy of aboBoNT-A and onaBoNT-A for upper limb spasticity (ULS).

METHODS

DIRECTION (NCT04936542), a phase IV, randomized, double-blind, crossover study, involved 72 sites. Patients stratified by botulinum toxin A status (naïve/non-naïve) were randomized (1:1) to aboBoNT-A 900U followed by onaBoNT-A 360U (one cycle each), or vice versa. Muscles (wrist/finger flexors, biceps brachii) were injected with a fixed volume, using instrument-guided injection techniques. Participants fulfilling retreatment criteria received a second cycle at Week 12; otherwise, they were reassessed every 4 weeks (to Week 24) until requiring retreatment. Primary analyses tested non-inferiority based on treatment-emergent adverse events (TEAEs) from injection to Week 12 using a 5% non-inferiority margin [non-inferiority demonstrated if upper bound of the 80% confidence interval (CI) of the adjusted difference in TEAE rates was < 5%]. Secondary analyses compared duration of response based on time to symptom re-emergence.

RESULTS

Overall, 464 patients [mean (standard deviation) age 56.8 (13.1) years, 34.1% female] were randomized (aboBoNT-A → onaBoNT-A [n = 231]; onaBoNT-A → aboBoNT-A [n = 233)]. Baseline characteristics were similar in both sequence arms. Adjusted rate of TEAEs for aboBoNT-A (20.3%) was non-inferior to onaBoNT-A (23.0%); adjusted difference (aboBoNT-A - onaBoNT-A) was - 2.7% (80%CI - 6.2%, 0.9%). Adjusted mean duration of response was 99.3 days for aboBoNT-A and 96.3 days for onaBoNT-A; adjusted difference of 3.0 (80%CI 0.2, 5.9) days favoring aboBoNT-A (p = 0.17; statistically significant under the pre-specified α = 0.20 framework). Longer duration of response with aboBoNT-A versus onaBoNT-A was seen across most subgroups over a fixed-interval follow-up.

CONCLUSION

In this first head-to-head study of aboBoNT-A and onaBoNT-A in ULS, the aboBoNT-A TEAE rate was non-inferior to onaBoNT-A. At 90% of the maximum unit dose for adult ULS in the approved label for each formulation, duration of response was 3 days longer with aboBoNT-A than onaBoNT-A. These findings may support informed therapeutic decision-making.

TRIAL REGISTRATION: ClinicalTrials.gov: NCT04936542; EudraCT: 2023-509196-16-00.