FDA Issues Boxed Warning for Copaxone and Other MS Drugs, Highlighting Safety Concerns in Multiple Sclerosis Treatment Landscape

The U.S. Food and Drug Administration (FDA) has added a new boxed warning to multiple sclerosis (MS) therapies containing glatiramer acetate, including Teva Pharmaceuticals' Copaxone, due to the risk of severe and potentially life-threatening allergic reactions. This development comes amid ongoing challenges in the MS treatment space, including recent setbacks in clinical trials and regulatory decisions.

FDA Safety Alert: Anaphylaxis Risk in Glatiramer Acetate Therapies

The FDA's decision to implement a boxed warning—its most serious safety signal—follows the detection of 82 cases of anaphylaxis worldwide from December 1996 through May 2024. These cases, linked to the use of glatiramer acetate, resulted in six patient deaths and 64 hospitalizations. The warning applies to all glatiramer acetate-based MS treatments, including Copaxone, Pendopharm's Glatect, and Sandoz's Glatopa.

According to the FDA's announcement, while most anaphylaxis cases occurred within an hour of dosing, 19 complications arose more than one year after initiating treatment. The agency emphasized that the reported cases likely underestimate the true incidence, as they only include reports submitted to the FDA and found in medical literature.

In light of these findings, the FDA recommends that patients discontinue the drug if they experience symptoms consistent with anaphylaxis, such as wheezing, difficulty breathing, and swelling. Healthcare providers are advised to monitor patients closely, as initial anaphylaxis symptoms may be mistaken for common post-injection reactions.

Implications for Teva and the MS Treatment Landscape

This safety update deals a significant blow to Teva Pharmaceuticals, whose MS drug Copaxone has already faced challenges in recent years. Once a blockbuster treatment generating $3.2 billion in U.S. sales at its peak in 2013, Copaxone's revenue has declined due to generic competition. Teva forecasted around $500 million in 2024 sales for Copaxone, down from $590 million in global sales in 2023.

The boxed warning adds to Teva's recent troubles, including a $450 million settlement in October to resolve kickbacks and price-fixing allegations from the U.S. government. Additionally, the European Commission fined Teva 462.6 million euros ($503 million) for alleged "abusive conduct" aimed at delaying competition and prolonging Copaxone's exclusivity.

Broader Challenges in MS Drug Development

The safety concerns surrounding glatiramer acetate therapies highlight the complexities and risks associated with MS treatment development. Recent months have seen several setbacks in the field:

1. In October 2024, Sanofi and Denali Therapeutics discontinued the mid-stage development of oditrasertib, an oral inhibitor of the RIPK1 protein, following disappointing data in a Phase II study.

2. Sanofi's 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. However, the drug later showed promise in slowing the onset of disability progression in patients with non-relapsing secondary progressive multiple sclerosis.

3. In March 2024, the FDA declined to approve Viatris and Mapi's long-acting glatiramer acetate injection for undisclosed reasons.

These developments underscore the ongoing challenges in developing safe and effective treatments for multiple sclerosis, a complex and debilitating neurological condition affecting millions worldwide.