Glatiramer acetate

Lore & Background

Glatiramer acetate was originally discovered at the Weizmann Institute of Science. It is a random polymer composed of four amino acids found in myelin basic protein, the antigen that stimulates an autoimmune reaction in people with multiple sclerosis. The medication is thought to act by modifying immune processes, shifting T cells from proinflammatory Th1 to regulatory Th2 cells that suppress inflammation, and may act as a decoy diverting the autoimmune response.

Three main clinical trials demonstrated its safety and efficacy: a single-center double-blind placebo-controlled trial with 50 patients; a two-year multi-center randomized double-blind placebo-controlled trial with 251 patients; and a double-blind MRI study with 239 patients. A 15-year followup of the original trial suggested reduced relapse rates and decreased disability progression in patients who continued glatiramer, though the groups were not necessarily comparable as it was no longer randomized.

Glatiramer acetate is approved in the United States to reduce the frequency of relapses, but not for reducing the progression of disability. Observational studies, but not randomized controlled trials, suggest it may reduce progression of disability. It is administered by subcutaneous injection.

Reader's Guide

Glatiramer acetate holds significance as a long-standing treatment for relapsing forms of multiple sclerosis, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease. Its approval in the United States in 1997 and subsequent approvals across Europe and other countries established it as a key immunomodulator. The medication's mechanism, though not fully elucidated, involves shifting T-cell populations and potentially acting as a decoy for autoimmune attacks on myelin.

A 2010 Cochrane review concluded that glatiramer acetate had partial efficacy in relapse-related clinical outcomes but no effect on disease progression, which is reflected in its FDA approval for reducing relapse frequency only. The drug's legacy includes controversy over patent evergreening: after the original chemical patent expired in 2015, Teva obtained new patents for long-acting formulations, which were later invalidated for obviousness. In 2024, the European Commission fined Teva €462.6 million for misuse of the patent system and disparagement to delay rival producers.

Adverse effects include injection site reactions in about 30% of users, flu-like symptoms in about 10%, and a rare but serious risk of anaphylaxis. The drug remains on the World Health Organization's List of Essential Medicines, underscoring its continued importance in multiple sclerosis therapy.

Did You Know?

• Glatiramer acetate is a mixture of random-sized peptides composed of glutamic acid, lysine, alanine, and tyrosine, the four amino acids found in myelin basic protein.
• A 15-year followup of the original trial suggested reduced relapse rates and decreased disability progression, but the groups were not necessarily comparable as it was no longer randomized.
• In October 2024, the European Commission fined Teva €462.6 million for misuse of the patent system and disparagement to delay rival producers of glatiramer acetate.
• The drug is approved to treat a first episode anticipating a diagnosis of multiple sclerosis, even though conclusive diagnosis requires two or more episodes.