Ipsen announces positive results from Phase IIIb/IV ENGAGE study of the combination of Dysport® (abobotulinumtoxinA) with Guided Self-rehabilitation Contracts in adult patients with upper and lower limb spastic hemiparesis

Results presented at the International Congress of Parkinson’s Disease and Movement Disorders (MDS) in Nice, France, 22-26 September 2019

Paris (France), 23 September 2019 – Ipsen (Euronext: IPN; ADR: IPSEY) today announced first results from the ENGAGE study which reports that simultaneous treatment with Dysport of both upper and lower limb spasticity in adult patients along with a Guided Self-rehabilitation Contract (GSC) – a personalized diary-based rehabilitation program – improved patients’ voluntary movement as measured by a composite active range of motion (CXA) outcome.1 Results from the study will be presented at the MDS International Congress in Nice, France, September 22-26, 2019 as poster #13705 and poster #13711.

ENGAGE is the first study to investigate treatment with Dysport in patients with spastic hemiparesis in both upper and lower limbs in combination with GSC. The primary efficacy endpoint of this international, prospective, single-arm study was the percentage of patients classified as responders at week six after the second injection, according to the CXA in the primary treatment target (PTT) limb.1

Professor Jean-Michel Gracies, Professor and Chair in the Department of Neurorehabilitation at Hospital Henri Mondor, in Créteil, France, and the primary investigator for ENGAGE said: “This study provides insight into treatment strategies that can improve the outcomes of patients living with spastic paresis, specifically the role of Guided Self-rehabilitation Contracts combined with Dysport for the improvement of voluntary movement, an area of limited data availability. Importantly, stronger active motion improvements and a longer time to reinjection was seen in ENGAGE versus previous Dysport studies, which suggests a synergistic effect of adding a GSC intervention to treatment with Dysport for patients with UL and LL spasticity.”

Patients in the study received two open-label injection cycles of Dysport, together with personalized GSC. A total dose of 1,500 U Dysport was administered across the primary treatment target (PTT) and non-PTT limbs at each injection cycle. Dosing was determined by the investigators, providing ≥750 U was administered to the PTT limb. Results from the study show that 72.1% (98/136; 95% CI: 64.0, 78.9) of patients in the study were classified as responders, achieving the predefined CXA improvement threshold in the PTT limb of ≥35° in upper limbs (UL) or ≥5° in the lower limbs (LL).1 These favorable outcomes were corroborated by the time to reinjection. Investigators could re-inject Dysport per their clinical judgment. Mean time to reinjection was 110.1 days (standard deviation: 25.2 days) and median time to reinjection was 106.5 days (range: 78–157 days).1 The time to reinjection recorded in ENGAGE was longer compared with previous studies in UL and LL which did not include GSC.1,2,3,4 Safety data were consistent with the known profile of abobotulinumtoxinA.1

Systemic standardized rehabilitation protocols are not commonly used in the majority of abobotulinumtoxinA spasticity studies. Similarly, pivotal studies of Dysport in these patients have focused on either UL or LL treatment strategies and outcomes;2,3 however, in real-life clinical practice patients can present with spasticity simultaneously in both the UL and LL.

Importantly, and in contrast to previous pivotal studies of Dysport, ENGAGE also provided insight into healthcare professionals’ real-world muscle selection for the administration of Dysport as it allowed investigators the flexibility of choosing varied muscle groups in the primary target limb. Prior pivotal/phase 3 adult UL and LL studies have all previously defined the target muscle group as elbow, wrist or finger flexors (UL) and gastrocnemius complex (LL) for primary endpoint.2,3

In ENGAGE, each patient received a personalized GSC tailored to their individual needs and focused on their PTT limb.1 Patients were asked to carry out the exercises detailed in the GSC – with a minimum cumulative 10 minutes of submaximal self-stretch postures per muscle – on a daily basis throughout the study. Patients kept a diary of each of the exercises performed and were contacted via telephone every two weeks to check how the GSC therapy was being performed and to ensure the diary was being filled out every day.

Antony Fulford-Smith, Vice President Medical Affairs, Neurosciences, R&D, at Ipsen said: “Over the last two decades there has been a shift from patients being recipients of healthcare to active participants empowered in their own health journey. Through ENGAGE, we have been able to demonstrate for the first time the benefit of combining treatment with Dysport with a systematic rehabilitation protocol, validating the positive impact of encouraging patients to take an active role in their own treatment. At Ipsen, we are constantly searching for ways to improve disease management and comprehensive care with a patient-centred approach. By using active range of motion as its primary measure, ENGAGE offers important insights on the potential benefit of using Dysport with GSC combination therapy in the context of meaningful functional outcomes for patients.”

1 Gracies, J.M., et al. Concomitant treatment of spastic paresis in both upper and lower limbs with abobotulinumtoxinA combined with a prescribed guided self-rehabilitation contract; effect on active range of motion from the single-arm open-label ENGAGE study. Poster presented at International Congress of Parkinson’s Disease and Movement Disorders (MDS) 2019. Poster #1371.
2 Gracies, J.M., et al. Efficacy and safety of abobotulinumtoxinA in spastic lower limb: Randomized trial and extension. Neurology 2017;89(22):2245-53. Available at: https://n.neurology.org/content/89/22/2245.long. Accessed July 2019.
3 Gracies, J.M., et al. Effects of abobotulinumtoxinA injections in upper limb spasticity. Muscle Nerve 2018;57(2):245–54. Available at: https://onlinelibrary.wiley.com/doi/full/10.1002/mus.25721. Accessed July 2019.
4 Gracies, J.M., et al. Safety and efficacy of abobotulinumtoxinA for hemiparesis in adults with upper limb spasticity after stroke or traumatic brain injury: a double-blind randomised controlled trial. Lancet Neurol. 2015;14(10):992-1001. Available at: https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(15)00216-1/fulltext. Accessed July 2019.
5 Gracies, J.M., et al. Guided Self-rehabilitation Contracts combined with simultaneous injections of abobotulinumtoxinA into upper and lower limbs in spastic hemiparesis: baseline data from the ENGAGE study. Poster presented at International Congress of Parkinson’s Disease and Movement Disorders (MDS) 2019. Poster #1370.
6 American Association of Neurological Surgeons. Spasticity. Available at: https://www.aans.org/Patients/Neurosurgical-Conditions-and-Treatments/Spasticity. Accessed July 2019.
7 National Institute of Neurological Disorders and Stroke. Spasticity Information Page. Available at: https://www.ninds.nih.gov/disorders/all-disorders/spasticity-information-page. Accessed July 2019.
8 Chih-Lin Kuo, C.-H., Hu, G.-C. Post-stroke Spasticity: A Review of Epidemiology, Pathophysiology, and Treatments. Int. J. Gerontol. 2018;12(4):280-284. Available at: https://www.sciencedirect.com/science/article/pii/S1873959818300073. Accessed July 2019.
9 Pirazzini, M., Rossetto, O., Eleopra, R. & Montecucco, C. Botulinum Neurotoxins: Biology, Pharmacology, and Toxicology. Pharmacol. Rev. 200–235 (2017). doi:10.1124/pr.116.012658
10 Jitpimolmard, S., Tiamkao, S. & Laopaiboon, M. Long term results of botulinum toxin type A (Dysport) in the treatment of hemifacial spasm: a report of 175 cases. J Neurol Neurosurg Psychiatry (1998).