Glatiramer Acetate Depot Demonstrates Sustained Long-Term Safety Profile as Potential MS Therapy

Daniel R. Wynn, MD

New data from a 52-week open-label extension of a phase 3 study (NCT04121221) showed that treatment with glatiramer acetate (GA) depot (Mapi Pharma) was safe and tolerable among patients with relapsing multiple sclerosis (MS). Overall, the favorable long-term safety profile, combined with a more convenient administration regimen of once every 4 weeks, support GA depot as a way to optimize patient care.¹

These data were presented at the 2024 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum, held February 29 to March 2, in West Palm Beach, Florida, by investigator Daniel R. Wynn, MD, a neurologist in Northbrook, Illinois. In the study, the most frequently reported treatment-emergent adverse events (TEAEs) included injection site reactions (ISRs), pyrexia, influenza-like illness, body temperature increase, and headache; however, these TEAEs were considered mostly mild or moderate (98.3% of events).

GA Depot, composed of extended-released microspheres that are administered intramuscularly, typically every 28 days, remains currently under review by the FDA. Data from the original double-blind, placebo-controlled portion of the phase 3 study served as the supportive data for the agent’s new drug application, which was accepted in August 2023. The agency is expected to have a decision on the therapy by March 8, 2024.²

In total, 736 patients of the 821 who completed the placebo-controlled period moved onto the OLE where they continued to receive GA Depot every 4 weeks for an additional 52 week period. Within this group, 416 had previously received placebo (pGA) and 347 continued to receive GA Depot (cGA) treatment. Overall, 625 (81.9%; pGA Depot: n = 332; cGA Depot: n = 293) completed the OLE period.

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 cGA Depot group compared with the GA Depot 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%).

Additional data from the OLE showed that the incidence of TEAEs leading to early discontinuation, which included ISRs, was lower in the cGA Depot group (8 patients, 2.3%) than in the pGA Depot group (20 patients, 4.8%). Regardless of whether patients stayed on treatment or switched from placebo, there were no clinically meaningful changes in physical examinations, serum biochemistry values, hematology values, vital signs, and ECG.

READ MORE: Susceptibility-Weighted Imaging Features Show Promise in Distinguishing AQP4-Negative-NMOSD From MS

In the original double-blind period of the study, treatment with GA Depot resulted in a 30% statistically significant reduction of annualized relapse rate relative to placebo (P = .0066). In addition to positive findings on the primary end point, GA Depot-treated patients had a 28.5% reduction in cumulative new enhancing T1 lesions (P = .0083) and a 17.3% reduction of cumulative number of new or newly enlarging hyperintense T2 lesions (P = .0305) over the 52-week period. Mean Expanded Disability Status Scale scores were also consistently and statistically significantly (P = .0193) reduced in the GA Depot arm.³

At the time of the NDA acceptance, Rajiv Malik, president at Viatris, said in a statement that, "Our application is backed by Phase III efficacy and safety data, and we believe, when approved, GA Depot could improve patient experience through fewer injections, greater tolerability and increased compliance. This milestone gives us further confidence in the strength of our GA Depot clinical program, and we look forward to continuing to work closely with FDA to bring access to this important complex medicine to patients."

GA Depot is also currently being investigated in a phase 2a study of patients with progressive MS, a form of the disease that has 1 approved therapy. At the 2022 Consortium of Multiple Sclerosis Centers Annual Meeting, 1-year interim data from the trial suggested that the agent is safe and effective for this patient population, based on the low rate of AEs detected and the stable EDSS for both men and women. In total, 69.2% of individuals treated with glatiramer acetate depot had no evidence of progression. On MRI analysis, patients had –0.89% change in brain volume from baseline to 1 year and –0.34% change from 6 months to 1 year. Similarly, these patients saw a –2.59% and –1.31% change in cortical volume from the same time points, respectively.⁴

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REFERENCES
1. 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.
2. Viatris and Mapi Pharma announce FDA acceptance of new drug application filing for GA Depot for the treatment of relapsing forms of multiple sclerosis. Viatris. August 7, 2023. Accessed August 7, 2023. https://www.prnewswire.com/news-releases/viatris-and-mapi-pharma-announce-fda-acceptance-of-new-drug-application-filing-for-ga-depot-for-the-treatment-of-relapsing-forms-of-multiple-sclerosis-301894145.html
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. Fletcher S, Kimelman NB, Danon U, et al. Glatiramer acetate depot (extended release) phase 2a study in patients with primary progressive multiple sclerosis: safety and efficacy 1 year interim snapshot analysis. Presented at: CMSC Annual Meeting; June 1-4, 2022; National Harbor, MD.