3-Year Findings Highlight Potential Therapeutic Benefits of GA Depot in Progressive MS

Ehud Marom

A new interim analysis of a phase 2 study of patients with progressive multiple sclerosis (MS) showed that treatment with glatiramer acetate (GA) depot (Mapi Pharma) was safe and resulted in stable scores on Expanded Disability Status Scale (EDSS) over a 3-year period. Overall, the data supports further investigation in a global, phase 3 double-blinded study.¹

Presented at the 2025 Americas Committee for Treatment & Research in Multiple Sclerosis (ACTRIMS) Forum, held February 27-March 1 in West Palm Beach, Florida, the interim analysis provided data based on varying patient treatment duration. In the study, patients with primary progressive MS (PPMS), aged 18-65, had mean EDSS scores of 5.1 at baseline and 4.9 at 3 years, suggesting stabilization of disease progression with treatment. Notably, during that time, there was only 1 case of 12-week confirmed disability progression (CDP).

Led by Ehud Marom, president and chief executive officer at Mapi Pharma, 89.7% of patients maintained stability in the 9-Hole Peg Test (9HPT) while 79.3% did so on the Timed 25-Foot Walk test over the 3-year period. Notably, during this time period, 69.0% of patients exhibited no evidence of progression (NEP), otherwise showing absence of clinical or radiological signs indicating worsening disability. Using MRI, volumetric analyses revealed brain volume changes of –0.77% at year 1, –1.46% at year 2, and –2.14% at year 3 of treatment. In addition, treatment with the long-acting, once-monthly treatment resulted in neocortical brain volume changes of –1.97% at 1-year, –2.09% at 2-years, and –3.30% at 3-years.

Overall, 83% of adverse events (AEs) were mild, with lower AE and injection site reaction (ISR) rates observed in the 25 mg dose compared to the 40 mg dose (0.20 vs. 0.49 for AEs; 0.01 vs. 0.15 for ISRs). While three serious adverse events (SAEs) occurred in the 40 mg group (two unrelated and one possibly related), none were reported in the 25 mg group, and no unexpected AEs were observed.

READ MORE: Phase 4 Study to Test Switch From Anti-CD20 Therapy to Ozanimod in Stable MS

GA Depot, a long-acting injection version of the approved glatiramer acetate (Copaxone; Teva Pharmaceuticals), is designed to be administered as an intramuscular injection once every 4 weeks. In early 2024, the FDA issued Mapi Pharma a complete response letter (CRL) for the agent as a potential treatment for relapsing MS, with few details given on the reasons behind the CRL. At the time, the company stated it was reviewing the content of the CRL and would determine the next steps to advance the treatment.²

The CRL was in reference to a new drug application (NDA) submission that included pivotal data from a phase 3, multinational, double-blind, placebo-controlled study (NCT04121221). In the 1016-patient study, treatment with GA Depot led to a statistically significant reduction of annualized relapse rate (ARR) relative to placebo (P = .0066) over a 52-week period.³

Included in the phase 3 study were patients with relapsing-remitting MS and active secondary progressive MS, aged 18-55, who were randomly assigned to 40 mg of GA Depot or placebo once every 4 weeks for a total of 13 doses. At 52 weeks, the therapy showed a 28.5% reduction in cumulative new enhancing T1 lesions (P = .0083), a 17.3% reduction in cumulative new or enlarging T2 lesions (P = .0305), and significant reductions in mean EDSS scores (P = .0193). Overall, compliance was high (99%), with 93.4% of patients opting to continue to the 52-week, open-label extension (OLE).

In the OLE, GA Depot was considered safe and tolerable among treated patients, with AEs like ISRs, pyrexia, influenza-life illness, body temperature increase, and headache observed. Between those who switched from placebo and participants who stayed on GA Depot into the OLE, the number of events/exposures to TEAEs in the OLE period were lower for those in the continuous GA Depot (cGA) group compared with those switching from placebo to GA Depot (pGA) group during the placebo-controlled period (2.46 person-years [PYs] vs 5.89 PYs). In addition, the incidence of serious TEAEs was lower in the cGA Depot group (4 patients, 1.2%) than in the pGA Depot group (10 patients, 2.4%).

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REFERENCES
1. Marom E, Kolb H, Popper L, et al. P095. Glatiramer Acetate Depot Extended-Release Phase IIa Study in Patients with Primary Progressive Multiple Sclerosis: Safety & Efficacy Snapshot Interim Analysis. Presented at: 2025 ACTRIMS Forum; February 27-March 1; West Palm Beach, FL. ABSTRACT P095.
2. Viatris and Mapi Pharma Statement Regarding New Drug Application for GA Depot. News Release. Viatris. Published March 11, 2024. Accessed February 28, 2025. https://newsroom.viatris.com/press-releases?item=123816
3. Miller AE, Popper L, Berger JR, et al. Results of a Phase III, Multinational, Double Blind, Placebo-Controlled Study in Subjects with Relapsing Forms of Multiple Sclerosis to Assess the Efficacy, Safety and Tolerability of GA Depot, a Long-Acting IM Injection of Glatiramer Acetate, Administered Once Every Four Weeks. Presented at ACTRIMS Forum 2023; February 23-25; San Diego, California. Abstract P087.
4. Miller A, Wynn D, Weinstock-Guttman B, et al. Safety and tolerability of glatiramer acetate depot: results of phase 3 open label period. Presented at: 2024 ACTRIMS Forum; February 29-March 2; West Palm Beach, FL. Abstract P100.