GA Depot for multiple sclerosis

Last updated Feb. 21, 2025, by Marisa Wexler, MS
Fact-checked by Ines Martins, PhD

What is GA Depot for MS?

GA Depot is a long-acting formulation of glatiramer acetate under clinical investigation for relapsing forms of multiple sclerosis (MS) and primary progressive MS (PPMS).

The active ingredient in the medication is approved for relapsing MS under the brand name Copaxone, and in generic formulations. These available forms of glatiramer acetate are injected under the skin, either daily or three times per week.

Mapi Pharma, which is developing GA Depot in collaboration with Viatris, designed its therapy to be given into the muscle instead, via an intramuscular injection once per month. The slow-release formulation would mean less frequent dosing for MS patients.

The companies submitted an application in 2023 seeking U.S. Food and Drug Administration (FDA) approval to treat relapsing forms of MS. The regulatory agency in early 2024 declined to approve it, issuing a complete response letter giving the companies the opportunity to amend their submission. No details from the letter were shared, but the companies said they would work to determine the next steps for GA Depot.

Therapy snapshot

How does GA Depot work in MS?

Glatiramer acetate, the active agent in GA Depot, is a synthetic (human-made) small protein designed to mimic a piece of myelin, the fat-rich substance that covers nerve cells. Myelin is attacked by the immune system in MS, leading to progressive neurodegeneration.

The compound in GA Depot was discovered in the 1970s while researchers were working on a new animal model of MS.

Scientists expected glatiramer acetate would promote MS-like disease, but they found that it actually prevented the disorder from developing. This unexpected discovery paved the way for the molecule’s development as an MS treatment.

While the precise mechanism of action for glatiramer acetate is not completely understood, it is broadly thought to modulate the immune system to reduce the inflammatory attack that drives MS.

GA Depot is a newer formulation made of microspheres that slowly release glatiramer acetate molecules into circulation over about 30 days, enabling less frequent dosing. The medication was found equivalent to older formulations in delaying disease onset and severity in mouse models of MS.

How will GA Depot be administered in MS?

GA Depot is designed to be given once per month via an intramuscular injection.

The medication has been tested in clinical trials at doses of 40 mg or 80 mg once per month in relapsing MS patients. As the 40 mg dose was better tolerated in an early trial, it was selected for further testing in a Phase 3 trial.

An ongoing Phase 2 study in PPMS is testing monthly injections containing 25 or 40 mg of GA Depot.

GA Depot in MS clinical trials

A Phase 1/2 study (NCT02212886) investigated GA Depot in 25 people with relapsing-remitting MS (RRMS) who had been on Copaxone for at least one year before the trial. During the study, participants switched to treatment with GA Depot at doses of either 40 mg or 80 mg, given once every four weeks, for about a year.

Results showed the 40 mg dosage had a better safety and tolerability profile. The most common side effects associated with treatment involved reactions at the injection site, most commonly pain, hardened skin, swelling, and redness. Most of these reactions were mild and temporary.

There was one relapse recorded during the study, compared with two in the prior year, when participants had been treated with Copaxone. The vast majority of participants (84.6%) had no evidence of disease activity throughout the study, defined as no relapses, no new signs of disease activity on MRI scans, and no sustained disability worsening.

Participants who completed the one-year trial were able to enter an optional extension period designed to track the long-term effects of the medication. In the extension, all are receiving the 40 mg dose, given every four weeks for up to eight years.

Early results showed that after five years, 90% of participants continued to show no evidence of disease activity. The extension part concluded in late 2024.

Phase 3 trial in relapsing MS

Mapi, in collaboration with Viatris, launched a Phase 3 clinical trial (NCT04121221) to test GA Depot in people with relapsing forms of MS, including RRMS and active secondary progressive MS.

The study enrolled 1,016 adults, ages 18 to 55, who were randomly assigned to monthly injections of 40 mg of GA Depot or a placebo for about one year, for a total of 13 injections.

The trial met its main goal, with GA Depot significantly lowering the relapse rate by 30.1% compared with a placebo. Patients given the experimental medication experienced an average of 0.182 relapses per year, versus 0.26 relapses per year among those given a placebo. This reduction was comparable to findings from previous trials of Copaxone.

The therapy significantly reduced the number of lesions with active inflammation, by 28.5%, and the number of new or enlarging lesions by 17.3%. Patients also experienced a slower accumulation of disability.

After completing the one-year trial, 93.4% of patients opted to join an open-label extension study in which all received monthly injections of 40 mg of GA Depot for about one more year.

Phase 2 trial in PPMS

A Phase 2 study (NCT03362294) is investigating whether GA Depot can slow disability accumulation in people with PPMS. In all, 30 adults were enrolled and are receiving GA Depot, at monthly doses of 25 or 40 mg, for 148 weeks (nearly three years).

The study’s main goal is to assess the therapy’s safety in this patient population. Efficacy measures include the proportion of patients with confirmed disability progression, or an increase in Expanded Disability Status Scale (EDSS) scores sustained for at least three months; sustained worsening in walking function and dexterity; and changes in brain volume.

An interim analysis of 29 trial participants, six of whom had completed the three years of follow-up, revealed no unexpected safety-related findings. Assessments of disability, dexterity, and walking ability were stable over time while the participants were on treatment. Across both dosing groups, 4.4% of patients experienced confirmed disability progression, about 30% had confirmed declines in walking function, and 6.9% had confirmed worsening in dexterity.

No evidence of progression, defined as no sustained worsening in EDSS scores, walking ability, and dexterity, was observed in 72.4% of patients. The 25 mg dose was safer and better tolerated than the higher dose, while still showing favorable efficacy, the researchers noted.

Common side effects of GA Depot

The most common side effects of GA Depot reported in MS clinical trials included:

• injection site reactions, such as swelling, pain, redness, or hardening of the skin
• general weakness.

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