FDA declines to approve GA Depot as treatment for relapsing MS

The U.S. Food and Drug Administration (FDA) has decided not to approve an application seeking clearance of GA Depot — a long-acting formulation of glatiramer acetate — for the treatment of relapsing forms of multiple sclerosis (MS).

Importantly, this is not a rejection of the application for the therapy’s approval, as submitted by developers Mapi Pharma and Viatris. Instead, the regulatory agency issued a complete response letter, or CRL, that, according to an FDA webpage, is sent to “indicate that the review cycle for an application is complete and that the application is not ready for approval.”

The CRL is designed to allow developers to do any needed course correction, and provides them with an opportunity to amend their submission so that it potentially could be approved in a later review.

Mapi and Viatris will now review the full content of the FDA’s letter to determine the appropriate next steps for GA Depot’s development, according to a press release from Viatris. No details were provided by Viatris.

“The companies continue to believe in the potential of the product to provide an important new treatment advancement for patients with multiple sclerosis,” the release stated.

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The FDA sent the CRL to Mapi, which is co-developing GA Depot with Viatris. The medication is a long-acting formulation of glatiramer acetate, the active ingredient in the approved therapy Copaxone, which also is available in generic formulations.

That active ingredient has been used for many years to treat relapsing forms of MS — including  clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS) and active secondary progressive MS (SPMS).

Unlike Copaxone and its generics, however, GA Depot needs to be administered only once a month rather than either three times weekly or once daily.

GA Depot contains extended-release microspheres, which are tiny particles that slowly release glatiramer acetate into the bloodstream over time. This enables the medication to remain at therapeutic levels for longer periods of time, thereby requiring less frequent injections. The novel formulation also is given via intramuscular, or into-the-muscle, injections. Copaxone and its generics, meanwhile, are given as a subcutaneous or under-the-skin therapy.

The regulatory application, which the FDA agreed to review last August, was backed by data from a Phase 3 clinical trial (NCT04121221) involving 1,016 adults, ages 18-55, with RRMS or active SPMS.

The participants, who had evidence of disease activity in the prior two years, were randomly assigned to receive once-monthly GA Depot (40 mg) or a placebo for a year, totaling 13 injections.

The trial met its main goal of demonstrating that GA Depot significantly reduced relapse rates by 30.1% relative to the placebo — a finding similar to observations made in previous trials of Copaxone. GA Depot also was associated with a slowing of disability accumulation and reductions in brain lesions compared with the placebo.

The most common side effects associated with GA Depot were mild injection site reactions. Analyses indicated that the intramuscular therapy has a favorable safety profile compared with subcutaneous glatiramer acetate formulations, notably including fewer injection site reactions and post-injection sensitivity reactions.

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Participants who completed the Phase 3 trial were given the option to enter an open-label extension (OLE) phase, where all would receive GA Depot for another year. A total of 763 patients joined.

Safety data from the OLE, presented at a recent conference, indicated that the rate of side effects during the second year of treatment was significantly lower than in the first year for patients who were continuously on GA Depot. The vast majority of side effects also were mild or moderate, and mostly included injection site reactions, fever or elevated body temperature, flu-like symptoms, and headache.

Significant improvements in overall life quality also were observed from the end of the main trial to the end of the OLE, according to other data presented at the conference. A significantly higher proportion of patients reported a maintained or improved life quality than a life quality decline after two years of treatment.

By the end of the OLE, most patients reported no problems across life quality domains, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. More than 90% of patients reported being satisfied with the treatment after both the main trial and the OLE.

An ongoing, open-label Phase 2 clinical trial (NCT03362294) also is evaluating GA Depot’s safety and efficacy. That study involves 30 adults with primary progressive MS, ages 18-65, all of whom will be treated for about three years.

Interim trial data indicated that GA Depot was well tolerated, and most treated patients had not experienced disability progression after one year.

In the release announcing the FDA letter, Viatris did not provide any details as to its content. The company did note that “the receipt of this CRL does not result in a change to Viatris’ 2024 financial guidance or its new product revenue range of $450M-$550M.”