Objective:

To evaluate efficacy, safety, and immunogenicity over multiple treatments of DaxibotulinumtoxinA for Injection (DAXI; DAXXIFY™), a novel botulinum toxin type A, in subjects with cervical dystonia (CD). 

Background:

Pooled Phase 3 results are presented from placebo-controlled, single-dose (ASPEN-1) and open-label extension (ASPEN-OLS) studies.

Design/Methods:

In ASPEN-1, 301 adults with moderate-to-severe CD were randomized 1:3:3 (placebo:DAXI 125U:DAXI 250U) and followed for ≤36 weeks. In ASPEN-OLS, 357 subjects (271 from ASPEN-1 and 86 newly enrolled subjects) received up to 4 treatments of DAXI 125U, 200U, 250U, or 300U based on investigator decision. Re-treatment in ASPEN-OLS was based on loss of 80% of peak treatment effect or subject request and investigator judgment. 

Results:

Across both studies, 382 subjects received 1240 DAXI treatments. Mean change from baseline (CFB) in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score, averaged over Weeks 4 and 6 post injection, increased over the 5 treatment cycles (-12.3 in ASPEN-1; -15.4, -17.7, -17.9, and -19.9 for Cycles 1-4 of ASPEN-OLS, respectively). Similar trends for increasing CFB over successive cycles were seen for TWSTRS subscales of pain (-3.0 to -5.8), disability (-3.5 to -6.0), and severity (-5.7 to -8.3). Clinical and Patient Global Impression of Change responder rates (≥2-point improvement) at Weeks 4 or 6 also increased from ASPEN-1 (58.8% and 52.2%) to Cycle 4 of ASPEN-OLS (83.1% and 69.2%).

Treatment-related dysphagia was reported in 2.7% of DAXI-treated subjects in ASPEN-1 and in 3.9%, 4.3%, 4.7%, and 3.1% of subjects in ASPEN-OLS Cycles 1-4, respectively (4.2% of 985 treatments in ASPEN-OLS). The incidence of treatment-induced anti-drug antibodies was low, with no observed trend in incidence over successive doses.

Conclusions:

Repeat treatments with DAXI were efficacious, safe and well tolerated, with a favorable immunogenicity profile.