Glatiramer acetate (previously called copolymer-1) is a synthetic copolymer composed of alanine, glutamine, lysine, and tyrosine, with some immunologic similarities to one of the important myelin components, myelin basic protein (MBP), without itself being encephalitogenic. The observation that it inhibits the animal model EAE prompted double-blind clinical trials.

The largest of these trials was a two-year, double-blind trial carried out in the United States involving 251 patients with RRMS (baseline EDSS 0–5). Treatment consisted of daily subcutaneous injections of 20 mg of glatiramer acetate or placebo. The primary end point was the annualised relapse rate, which was reduced by 29 percent in the group receiving active treatment. There also was a reduction in the percentage of patients remaining relapse-free and the median time to first relapse. A statistically significant favourable effect on EDSS progression was evident only with a less conservative data analysis, thereby providing a trend, but not significant proof for an effect on progression of disability. There has been a lack of MRI data for some years, but recently data from a nine-month, double-blind, placebo-controlled trial with a primary MRI end point demonstrated that glatiramer acetate administration is followed by a delayed reduction of blood–brain barrier permeability (peak effect is after a number of months rather than a few weeks for the interferons) and a suppression of new lesion development. This finding may result from the effect of glatiramer acetate in downregulating the immune response rather than a specific effect on the blood-brain barrier. Glatiramer acetate does not reduce T cell migration.
Long-term follow-up of the patients who participated in this trial suggests that glatiramer might have a favourable impact on long-term disability progression, but the interpretation of follow-up data is significantly limited by patients being lost to follow-up.

A large trial (Promise Trial) to evaluate the effects of glatiramer acetate over three years in patients with PPMS was terminated at a preplanned interim analysis, because the trial failed to demonstrate a treatment effect of glatiramer acetate.

Adverse effects of glatiramer acetate are usually mild, and include localised injection-site reactions and a systemic reaction occurring within minutes of administration of the drug (associated with chest pain, palpitations, or dyspnea, and always resolving spontaneously in less than 30 minutes). This reaction occurs in a small minority of patients, usually only once, and not necessarily after the first injection. Occasional patients develop lipoatrophy at injection sites and lymphadenopathy has been reported. Glatiramer acetate does not induce changes in liver function, blood count, or thyroid function. Consequently, the regular monitoring of blood work that is necessary with the IFNs is not needed for patients treated with glatiramer acetate.

Serum antibodies to glatiramer acetate also develop, but their presence seems to have no effect on the clinical benefit.

The apparent effect on reducing relapse rate might be due to blocking of the presentation of certain myelin antigens to T lymphocytes. Other proposed mechanisms of action include the induction of suppressor cells that migrate systemically to modulate the immune response within the nervous system (“bystander suppression”). Of great interest are the observations that glatiramer acetate-reactive cells may secrete growth factors that may enhance repair within the MS plaque, and that anti-glatiramer acetate antibodies may enhance remyelination.

In the opinion of the Committee, glatiramer acetate constitutes an effective therapy for patients with RRMS. Recent suggestions that the drug slows the rate of disability progression need to be confirmed by additional studies. Some patients seem to tolerate glatiramer acetate better than interferon beta during the first months of treatment.