The drugs’ active ingredient, glatiramer acetate, has been linked to more than 80 cases of anaphylaxis worldwide since December 1996 and six patient deaths.
The FDA on Wednesday added a new boxed warning to a class of multiple sclerosis therapies—including Teva Pharmaceuticals’ Copaxone—about a risk of severe and potentially life-threatening allergic reactions.
The drug in question is glatiramer acetate, an immunomodulatory peptide therapy that works by altering certain immune pathways associated with multiple sclerosis—though its exact mechanism of action has not yet been fully elucidated, according to Copaxone’s label. Aside from Copaxone, other drug brands that use glatiramer acetate for MS include Pendopharm’s Glatect and Sandoz’s Glatopa.
According to the FDA’s announcement, the new boxed warning—its most serious safety signal—comes after the agency detected 82 cases of anaphylaxis worldwide from December 1996 through May 2024. Of these, 19 complications arose more than 1 year after initiating glatiramer acetate treatment, while the majority occurred within an hour of dosing.
“The 82 worldwide cases include only reports submitted to FDA and found in the medical literature so there are likely additional cases about which we are unaware,” the regulator noted. While the cases of anaphylaxis were rare relative to how often the drug is administered, outcomes tended to be serious and required hospitalization or emergency visits for medical intervention. Six patients died of the adverse event.
In light of these new safety findings, the FDA recommends that patients discontinue the drug if they experience symptoms consistent with anaphylaxis, such as wheezing, difficulty breathing and swelling. If left unchecked, these symptoms can progress to include severe rashes and shock, the latter of which can be life-threatening.
Wednesday’s new safety warning illustrates how fraught the multiple sclerosis space can be, even for drugs that have already cleared the FDA’s regulatory gauntlet.
The space in recent months has seen several setbacks, including an October 2024 announcement from Sanofi and development partner Denali Therapeutics that they were discontinuing the mid-stage development of oditrasertib following disappointing data. Oditrasertib, an oral inhibitor of the RIPK1 protein, failed to significantly improve neurofilament light chain levels in the Phase II K2 study.
A month earlier, Sanofi also reported that its BTK inhibitor tolebrutinib missed its key outcome in two Phase III multiple sclerosis studies, GEMINI 1 and GEMINI 2, failing to significantly lower relapse rates. The asset saw redemption a few weeks later when it was found to slow the onset of disability progression by 31% in patients with non-relapsing secondary progressive multiple sclerosis.
In March 2024, the FDA declined to approve Viatris and Mapi’s long-acting glatiramer acetate injection for reasons that the partners did not disclose.
