Date: 2014-02-05
Type of information: Results
phase: 3
Announcement: results
Company: Ipsen (France)
Product: Dysport® Next Generation (DNG)
Action
mechanism: protein. Dysport® Next Generation is a ready-to-use liquid botulinum toxin A solution.
Disease: cervical dystonia
glabellar lines
Therapeutic area:
Country:
Trial
details: The Randomised, Double-blind and Open Label Phase, Active and Placebo Controlled phase III trial in
Cervical Dystonia included 369 patients. It included BoNT-A naïve or non-naïve patients suffering from this disease for at least 18 months. In thedouble blind part of the study, patients were randomly assigned to treatment with DNG, Dysport® or placebo injections into the neck muscles. The patients then entered into an open label part of the study wherein they could receive up to 5 injections of DNG. The primary endpoint of the study was the assessment of DNG efficacy and safety, as compared to placebo and Dysport®, in the treatment of patients with cervical dystonia.
The Double Blind, Randomised, Placebo and Active Comparator Controlled Phase II trial in glabellar lines
included 176 patients. The primary endpoint of the study was the assessment of DNG efficacy and safety, as compared to placebo and Dysport®, in the treatment of patients with moderate to severe glabellar lines. DNG was clinically and statistically superior to placebo and comparable to Dysport® at the dose of 50 units after single dose at week 4, as assessed by a co-primary endpoint composed of the “investigator live assessment” and “the subject self-assessment”. Based upon “the investigator live assessment”, the responder rate was 91% for DNG and 77% for Dysport®, respectively. Based upon the “patient selfassessment”, the responder rate was 86% for DNG and 83% for Dysport®, respectively. The responder rate corresponds to the number of patients who had an improvement of their wrinkles from “severe/moderate wrinkles” to “mild/no wrinkle” on any scale.
The safety profile observed of DNG after unique and repeated dose was excellent and consistent with the
known safety profile of Dysport®.
Latest
news: * On February 5, 2014, Ipsen has announced the results of the international Phase III clinical trial of Dysport® Next Generation (DNG) in cervical dystonia and the results of the European Phase II clinical trial of DNG in glabellar lines. In the light of these results, Ipsen announces its intention to file the first ready-to-use liquid toxin A in Europe and in the Rest of the World1 (ROW). DNG was clinically and statistically superior to placebo in the cervical dystonia Phase III study at the dose of 500 units at week 4 after single dose (adjusted mean reduction of 12.5 with DNG versus 3.9 with placebo as assessed by the Toronto Western Spasmodic Torticollis Rating Scale, or TWSTRS, total score). When compared to Dysport®, DNG did not demonstrate the statistical non-inferiority in efficacy at week 4 (adjusted mean reduction of 12.5 with DNG versus 14.0 with Dysport® in TWSTRS total score). This efficacy difference is unlikely to be of clinical relevance.
After repeated dose, DNG showed comparable efficacy to that of Dysport® as observed in former Phase III studies. DNG was clinically and statistically superior to placebo and comparable to Dysport® in the glabellar lines Phase II study at the dose of 50 units after single dose. Across the studies, DNG showed safety profiles consistent with the known safety profile of Dysport®.
Regarding DNG stability, analysis is still ongoing. The stability data trends are positive, providing confidence of achieving a commercially viable product. Ipsen is continuing stability testing to establish maximum shelf life across full product range. On the basis of these results and feedback from the Principal Investigator of the Phase III study, Ipsen intends to initiate a dialog with key agencies on the regulatory approach to file the first ready-to-use liquid toxin A in Europe and ROW.
