Long-Acting Glatiramer Acetate Appears Safe and Effective in Large Trial
Injecting a long-acting version of glatiramer acetate—GA Depot—intramuscularly every 28 days appears as safe and effective for treating relapsing multiple sclerosis (MS) as the currently available formulation that must be injected three times a week, according to the findings of a large, randomized trial presented in February at the Americas Committee for Treatment and Research in Multiple Sclerosis Forum 2023.
The phase 3 trial tested GA Depot, in which the drug is encapsulated in extended-release microspheres, on 1,016 participants.
All participants were included in the primary endpoint analysis—half in the placebo arm and half given GA Depot—but fewer participants were included in the secondary analyses. Both the cumulative number of T1 new enhancing lesions, as well as the number of new or newly enlarging hyperintense T2 lesions, were reported for 470 of participants in the placebo arm and 447 in the GA Depot arm.
Compared with patients with relapsing forms of MS who received a placebo, those who received the active drug had an annualized relapse rate (the trial's primary outcome) that was 30.1 percent lower at 52 weeks (p=0.0066).
The first secondary endpoint, the cumulative number of T1 new enhancing lesions, was 28.5 percent lower in the GA Depot arm compared with placebo at 52 weeks (p=0083). The second secondary endpoint, a post-hoc analysis of the number of new or newly enlarging hyperintense T2 lesions at 52 weeks, was 17.3 percent lower in those who had GA Depot (p=0.0305).
In addition, the mean Expanded Disability Status Scale (EDSS) was significantly lower in the GA Depot group (p=0.0193).
As expected, those receiving the active drug had a higher incidence of treatment-emergent adverse events, most commonly injection site reactions (ISRs), which were mostly mild. Of the 508 participants randomized to GA Depot, 274 (53.9 percent) reported no reactions. Another 69 participants (29.5 percent) randomized to active drug reported only one ISR, and 40 more (17.1 percent) reported only two ISRs. The remainder reported between three and seven ISRs.
“Conventional GA has been one of the mainstays of disease-modifying therapy for MS for decades," said the first author of the paper, Aaron E. Miller, MD, FAAN, medical director of the Corinne Goldsmith Dickinson Center for MS and a professor of neurology at the Icahn School of Medicine at Mount Sinai.
“The main benefit of GA Depot over the standard formulation is the dramatic reduction in the number of injections needed over a month," Dr. Miller told Neurology Today At the Meetings. “This should lead to better adherence, which should result in better real-world outcomes."
Dr. Miller noted that most of the sites for the international trial were in Eastern Europe, including many in Ukraine, where the war with Russia was underway in the latter stages of the trial. Dr. Miller said they turned to Europe for the trial because “in North America and Western Europe, there is a great reluctance to enroll patients in placebo-controlled trials that last more than a few months, given all the disease-modifying therapies we have. This was a one-year trial."
Eligibility criteria for the trial required that participants have relapsing MS with an EDSS no higher than 5.5, with at least one relapse in the prior year or at least two relapses in the prior two years.
Clyde E. Markowitz, MD, associate professor of neurology and director emeritus of the MS Center at the University of Pennsylvania's Perelman School of Medicine, said that while the long-acting version of the drug looks as safe and effective as the original version, “it's not a game changer. Most patients today use disease-modifying drugs that have higher efficacy than GA offers."
The new formulation, Dr. Markowitz said, might appeal to younger patients who present with mild disease activity on imaging.
“You could make a case that young people who are thinking about having kids, who are worried about immune suppression, would make a good candidate," he said.
Even so, he doesn't prescribe a lot of GA injections.
“We've taken a more aggressive approach of using drugs that have high efficacy," Dr. Markowitz said. “We're not using a lot of GA as first-line therapy."
The senior author of the poster presented at ACTRIMS, Ehud Marom, is a co-inventor of GA Depot and the founder and CEO of Mapi Pharma, which sponsored the trial. Aside from Joseph R. Berger, MD, FAAN, associate chief of the MS division and professor of neurology at the Hospital of the University of Pennsylvania, the other four coauthors of the paper are employees of Mapi.
Dr. Miller has received compensation from Mapi-Pharma as chairman of the steering committee for the GA Depot trial; research support from Genzyme/sanofi, Novartis, Roche/Genentech, and Corevitas; has been a consultant for Accordant Health Services (Caremark); Biogen Idec, Corevitas, EMD Serono, Mapi-Pharma, Roche/Genentech, Verana Health, and Viatris (Mylan); and has served on the speakers' bureau for Biogen Idec (unbranded disease awareness programs only); EMD Serono (unbranded journal club); Alexion (unbranded disease awareness programs only); Genentech (unbranded disease awareness programs only;and Horizon Therapeutics (unbranded disease awareness programs only). Dr. Markowitz has received consulting honorarium from Alexion, ANI, Banner Life Sciences Biogen, Bristol-Myers Squibb, EMD-Serono, Cycle Pharmaceuticals, Genentech/Roche, Genzyme/Sanofi, Horizon Therapeutics, Janssen/ Actelion, Novartis, Teva, and TG Therapeutics.
This article was originally posted to Neurology Today. Read the original article here.
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