PARIS -- (BUSINESS WIRE) -- Regulatory News:
Ipsen (Paris:IPN) (Euronext: IPN; ADR: IPSEY) today 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).
Pr. Werner Poewe (International Principal Investigator of the study) said: “This is the very first international Phase III trial to show that a liquid toxin A is safe and efficacious. Although the statistical non-inferiority criterion between DNG and Dysport® was not formally met in the Double Blind Phase of the trial, this is unlikely to reflect clinical meaningful differences between the two formulations. In addition, the Open Label Long Term data show sustained and robust efficacy of DNG with a good safety profile. These important results will help the medical community to assess the place of a ready-to-use liquid toxin A in the treatment options for patients suffering from cervical dystonia.”
Claude Bertrand, Executive Vice-President Research & Development and Chief Scientific Officer of Ipsen commented: “With these studies, we confirm our role of pioneer in the field of toxins and our leadership in developing innovative therapeutic solutions. Ipsen’s ambition is to become the first company to file a ready-to-use liquid toxin A, which should meet the expectations of physicians by potentially providing a new treatment option for patients.”
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 studies2.
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 ROW3.
Dysport® is an injectable form of botulinum toxin type A (BoNT-A), which is isolated and purified from Clostridium BTX-A bacteria. The product is supplied as a lyophilised powder.
Dysport® was first registered for the treatment of blepharospasm and hemifacial spasm in the United Kingdom in 1990, and is licensed in more than 75 countries for various indications including: blepharospasm, adult upper and lower limb spasticity, hemifacial spasm, spasmodic torticollis (previously referred to as cervical dystonia), paediatric spasticity due to cerebral palsy, axillary hyperhidrosis, and glabellar lines.
About Dysport® Next Generation
Dysport® Next Generation is a ready-to-use liquid botulinum toxin A solution. This product offers the advantage to simplify the preparation of the drug to be injected, help physicians focus on patient care and potentially increase safety by reducing the risk of preparation errors.
About the clinical studies
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 the double 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.
There was a statistically significant decrease in TWSTRS (Toronto Western Spasmodic Torticollis Rating Scale) score and an increase in proportion of patients responding to Dysport® and DNG vs. placebo (p < 0.001) at the dose of 500 units after single dose at Week 4. DNG was clinically and statistically superior to placebo with an adjusted mean reduction of 12.5 (versus 3.9 with placebo) in TWSTRS total score at week 4. When compared to Dysport®, DNG did not demonstrate the non-inferiority with an adjusted mean reduction of 12.5 (versus 14.0 with Dysport®) in TWSTRS total score at week 4.
Patients receiving DNG and Dysport® also reported an improvement in quality of life after single dose as compared to placebo. In the open label part of the study, the efficacy and quality of life improvement was maintained in patients receiving DNG. The safety profile of DNG after single and repeated dose was excellent and consistent with the known safety profile of Dysport®.
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 self-assessment”, 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®.
Ipsen is a global specialty-driven pharmaceutical company with total sales exceeding €1.2 billion in 2013. Ipsen’s ambition is to become a leader in specialty healthcare solutions for targeted debilitating diseases. Its development strategy is supported by 3 franchises: neurology, endocrinology and uro-oncology. Moreover, the Group has an active policy of partnerships. Ipsen's R&D is focused on its innovative and differentiated technological platforms, peptides and toxins. In 2012, R&D expenditure totalled close to €250 million, representing more than 20% of Group sales. The Group has close to 4,900 employees worldwide. Ipsen’s shares are traded on segment A of Euronext Paris (stock code: IPN, ISIN code: FR0010259150) and eligible to the “Service de Règlement Différé” (“SRD”). The Group is part of the SBF 120 index. Ipsen has implemented a Sponsored Level I American Depositary Receipt (ADR) program, which trade on the over-the-counter market in the United States under the symbol IPSEY. For more information on Ipsen, visit www.ipsen.com.
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1 Latin America, Middle East and Asia (ex Japan and China)
2 Truong D. et al. Mov. Disord., 2005; 20 (7) 783-791; Truong et al., Parkinsonism Relat Disord. 2010 Jun;16(5):316-23
3 Latin America, Middle East and Asia (ex Japan and China)