GA Depot is a long-acting formulation of glatiramer acetate that is under clinical investigation for relapsing forms of multiple sclerosis (MS) and primary progressive MS (PPMS).
The active ingredient in this medication is already approved for relapsing MS under the brand name Copaxone, as well as 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, designed its therapy to be injected into the muscle instead, once per month. The slow-release formulation would mean less frequent dosing for MS patients.
The therapy is being reviewed by the U.S. Food and Drug Administration for the treatment of relapsing forms of MS. A decision is expected by March 8, 2024.
Glatiramer acetate, the active agent in GA Depot, is a synthetic (man-made) small protein that’s 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 initially discovered in the 1970s when 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 a treatment for MS.
It is precise mechanism remains incompletely understood, but glatiramer acetate 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 the older formulations in delaying disease onset and severity in mouse models of MS.
GA Depot is designed to be given once per month via an intramuscular (into-the-muscle) injection.
The medication has been tested in clinical trials at doses of 40 or 80 mg once per month in relapsing MS patients. The 40 mg dose was better tolerated, and is being further studied in relapsing MS in a Phase 3 trial. An ongoing Phase 2 study in PPMS is testing doses of 25 or 40 mg once per month.
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 or 80 mg, given once every four weeks, for about a year.
Results showed that the 40 mg dosage had a better safety and tolerability profile. The most common side effects associated with treatment were 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, as 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 MRI lesions, and no sustained disability worsening.
Participants who completed the one-year trial were then 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, after five years, showed that 90% of participants continued to show no evidence of disease activity. This extension part is due to conclude in late 2024.
In collaboration with Viatris, Mapi 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 (SPMS).
The study ultimately enrolled just over 1,000 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 rate of relapses by 30.1% compared with a placebo. Overall, 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.
Participants who completed the one-year trial were invited to join an open-label extension study. A total of 93.4% of patients opted to join the extension, where they are receiving monthly injections of 40 mg GA Depot for about one more year.
An ongoing Phase 2 study (NCT03362294) also is investigating whether GA Depot can slow disability accumulation in people with PPMS. In all, the 30 adults in this trial will be given GA Depot for 148 weeks. The participants, ages 18 to 65, are receiving monthly doses of 25 or 40 mg.
The study’s main goal is to assess the therapy’s safety in this patient population. Treatment efficacy will be determined as the time to confirmed disability progression — an increase in the Expanded Disability Status Scale (EDSS) scores sustained for at least three months — as well as changes in brain volume. The EDSS measures how much patients are affected by their MS.
An interim analysis of 16 trial participants treated for up to 144 weeks revealed no unexpected safety-related findings. The analysis indicated that assessments of disability, dexterity, and walking ability were stable over time while on treatment. After one year, 69.9% of patients also had no evidence of disease progression.
The most common side effects of GA Depot reported in MS clinical trials included:
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The active ingredient in GA Depot, known fully as glatiramer acetate, is already approved for the treatment of multiple sclerosis. Glatiramer acetate is thought to modulate the immune system to reduce the inflammatory attack that drives MS. This experimental therapy, now in clinical trials, is designed to be administered once per month via injection into muscle. A slow-release formulation, it would allow less frequent dosing than the currently approved therapies, marketed as Copaxone and generics, which are given once daily or several times per week as an under-the-skin (subcutaneous) treatment.
Mapi, the company developing GA Depot, has already asked the U.S. Food and Drug Administration (FDA) to approve the therapy for relapsing forms of multiple sclerosis, based on promising data from completed a Phase 3 clinical trial. A final regulatory decision is expected by March 8, 2024.
Clinical trials testing GA Depot have not enrolled participants who were pregnant or breastfeeding. It is therefore unknown whether the experimental medication is safe for use in these situations. Other formulations of glatiramer acetate also have not been rigorously studied in pregnant people.
In an early clinical trial that enrolled patients who had been on stable Copaxone treatment for their multiple sclerosis, most who switched to GA Depot showed no signs of disease activity — including no relapses, disability worsening, or new MRI lesions — after one year of treatment.
Hair loss and weight gain have not been reported as side effects of GA Depot in clinical trials. Studies testing other formulations of glatiramer acetate also have not reported these side effects. Patients who experience unexpected reactions after starting a new medication are advised to consult their healthcare team.
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