Clinical Trials

Date: 2017-11-29

Type of information: Publication of results in a medical journal

phase: 3

Announcement: publication of results in Neurology

Company: Ipsen (France)

Product: Dysport® (abobotulinumtoxin A )

Action mechanism:

• protein. Dysport® is an injectable form of botulinum toxin type A (BTX-A), which is isolated and purified from Clostridium BTX-A bacteria. It inhibits the effective transmission of nerve impulses and thereby reduces muscular contractions. It is supplied as a lyophilized powder. Dysport® was first registered for the treatment of blepharospasm and hemifacial spasm in the United Kingdom in 1990, and is licensed in 82 countries for various indications including: blepharospasm, adult upper and lower limb spasticity, hemifacial spasm, spasmodic torticollis (ST) (previously referred to as cervical dystonia), pediatric lower limb spasticity due to cerebral palsy (CP), axillary hyperhidrosis, and glabellar lines. Dysport® is approved for the treatment of upper limb spasticity and pediatric lower limb spasticity in many international markets, but not in the United States. Dysport® is also approved for the treatment of adult lower limb spasticity in some European countries, but not in the United States.

Disease:

Therapeutic area: Neurological diseases - Neuromuscular diseases

Country:

Trial details:

• The Phase III study (NCT01251367) was a multi-center, prospective, open-label, multiple-cycle extension of the double-blind study (NCT01249404). The primary endpoint of the open-label study was long-term safety, with longterm efficacy as a secondary endpoint. During the first treatment cycle of the open-label study, all participants received Dysport® 1500 U except for those participants who experienced treatment-emergent adverse events (TEAEs) during the doubleblind phase, who received Dysport® 1000 U. For subsequent cycles, Dysport® 1000 U or 1500 U was administered based on the investigator’s judgment. Throughout the open-label study, the Dysport® tolerability profile remained consistent. The incidence of TEAEs decreased across repeated treatment cycles with both doses of Dysport®, with most TEAEs being mild to moderate. Overall, 19 participants withdrew due to TEAEs, 11 of which were considered to be treatment-related. Across all treatment cycles, 11 percent of participants experienced serious adverse events (SAEs). There were 2 deaths that both occurred in the Dysport® 1500 U group, 1 suicide and 1 respiratory failure, neither of which was considered to be treatment-related.
• Dysport® was shown to be efficacious across repeated treatment cycles. Muscle tone improvements observed in the double-blind study remained stable from Cycle 2 onwards, with -0.9 change from baseline in MAS GSC and -1.1 in MAS soleus (Dysport® doses combined). Physician global assessment (PGA) scores continued to improve with repeat treatment, reaching 1.9 by Week 4 of Cycle 4. In addition, participants experienced improvements in active function as assessed by the 10m comfortable barefoot walking speed test. Walking speed increased across repeated Dysport® treatment cycles, reaching an improvement from double-blind study baseline of 25.35 percent (95 percent confidence interval 17.48– 33.21) at Week 4 of Cycle 4. While the majority of patients in each open-label cycle were re-treated at Week 12, many had longerlasting results and were treated at Week 16 and beyond. (NCT01249404 and NCT01251367)

Latest news:

• • On November 29, 2017, Ipsen announced that detailed results from a Phase III randomized, double-blind, placebo-controlled study and its open-label extension study have been published in Neurology, demonstrating the efficacy and safety of Dysport® (abobotulinumtoxinA) in adult patients with lower limb spasticity following a stroke or traumatic brain injury.
• The international phase III registration study led to the FDA expanded approval of Dysport® for injection for the treatment of spasticity in adults, based on its supplemental Biologics License Application (sBLA) in lower limb spasticity, on June 16, 2017. This same study has been the basis for marketing authorization in other key markets, including the UK and Germany, in late 2016, and regulatory procedures are still ongoing in other countries.
• These two studies demonstrated the efficacy and safety of Dysport® in adults with hemiparesis who experienced lower limb spasticity. The results showed that, in this population, single Dysport® administration reduced muscle tone, while repeated administration over a year was well-tolerated and improved both walking speed and likelihood of achieving community ambulation. In the U.S., Dysport® has a boxed warning in its product label regarding distant spread of toxin effect. (Gracies JM, Esquenazi A, Brashear A, et al. Efficacy and safety of abobotulinumtoxinA in spastic lower limb: Randomized trial and extension. Neurology 2017 Nov 1. doi: 10.1212/WNL.0000000000004687.)

   

Is general: Yes