Results of a Phase III, Multinational, Double-blind, Placebo-controlled Study in Subjects with Relapsing Forms of Multiple Sclerosis (RMS) to Assess the Efficacy, Safety, and Tolerability of GA Depot, a Long-Acting IM Injection of Glatiramer Acetate, Administered Once Every Four Weeks
Aaron Miller1, Laura Popper2, Joseph Berger3, Nadav Kimelman4, Shai Rubnov4, Uri Danon4, Ehud Marom4
1Neurology, Icahn School of Medicine at Mount Sinai, 2Mapi Pharma Ltd., 3University of Pennsylvania School of Medicine, 4Mapi-Pharma
Objective:
To assess efficacy, safety and tolerability of GA Depot, a long-acting IM injection of glatiramer acetate, administered every four weeks, compared to placebo in a phase III randomized double-blind study in subjects with relapsing multiple sclerosis (RMS).
Background:
GA Depot consists of extended-release microspheres administered intramuscularly every 28 days.
Design/Methods:
1,016 subjects received GA Depot 40mg or placebo every four weeks for 52 weeks. Subjects were age 18-55 years and experienced at least one relapse in 12 months prior to screening or two relapses in 24 months prior. Primary endpoint was annualized relapse rate (ARR); secondary endpoints were MRI based. An optional open label extension study was available to subjects completing RCT.
Results:
Baseline characteristics were similar between arms. Primary analysis showed statistically significant (p=0.0066) reduction of 30% of ARR for the GA Depot arm compared to placebo. The 1st secondary endpoint of cumulative T1 new enhancing lesions showed statistically significant (p=0.0083) reduction of 28.5% in the GA Depot arm. The 2nd secondary endpoint post-hoc analysis of cumulative number of new or newly enlarging hyperintense T2 lesions at week 52 showed statistically significant (p= 0.0305) reduction of 17.3% for GA Depot subjects. Mean EDSS showed consistent statistically significant (p=0.0193) reduction. The GA Depot arm had an expected higher incidence of treatment emergent adverse events (TEAEs). Most common TEAEs were injection site reactions (ISR), mostly mild. For patients remaining in the study the observed compliance rate is ~99%.
Conclusions:
The significant treatment effect of GA Depot in reducing ARR (30%, p=0.0066), strengthened by MRI endpoints, supports the use of GA Depot as a DMT for RMS patients. GA Depot offer a preferable schedule than current regimens of GA leading to improved patient satisfaction and treatment. GA Depot administration regime is expected to result in fewer ISRs than other GA products.