Copaxone® (glatiramer acetate)
FDA-Approved Medications: New Data on Previously Approved Medications
Company: Teva Pharmaceuticals
- Dose: 20 mg/mL daily or 40 mg/mL three times weekly, self-administered subcutaneously
- Approved for RMS in 1996
Copaxone® (glatiramer acetate) is a synthetic protein that simulates myelin basic protein, a component of the myelin that insulates nerve fibers in the brain and spinal cord. Though its mechanism of action is not completely understood, this medication appears to work by blocking myelindamaging T cells. The Copaxone brand of glatiramer acetate was approved in 1996, and generic formulations have since become available.
Copaxone gained FDA approval for the treatment of RRMS based on five placebocontrolled studies. In the first two studies, a total of 301 individuals with RRMS with at least two exacerbations in the two years preceding the study were randomized 1:1 to Copaxone 20 mg/mL daily or placebo. In both studies, relapse rates and frequency were reduced in the Copaxone groups, but the sample sizes in both studies were small. In the third study, 481 individuals who had experienced demyelination (damage to protective fibers around nerves in the brain) within the previous 90 days and who showed lesions on MRI received Copaxone 20 mg/mL daily or placebo. After a maximum three-year follow-up period, time to a second exacerbation was significantly delayed in the Copaxone group compared with placebo.45
In the fourth study, 239 individuals who had suffered at least two exacerbations in two years and showed at least one enhancing lesion on MRI at screening were randomized to double-blind administration of Copaxone or placebo for nine months. During that period, all study participants underwent monthly MRI scans. At study’s end, the median cumulative number of T1-enhancing lesions was significantly lower in the Copaxone group compared with placebo (11 versus 17). In the fifth study, 1,404 people with RMS received Copaxone 40 mg/mL (943) or placebo (461) three times weekly for one year. At study’s end, the Copaxone group had experienced fewer confirmed relapses and showed significantly fewer cumulative new or enlarging T2 lesions and cumulative T1-enhancing lesions, compared with placebo.45
New data from an analysis of diseasemodifying therapies point to the long-term effectiveness of glatiramer acetate in delaying disability and preserving function in MS. Researchers in the United Kingdom compared 755 individuals with RRMS who had received glatiramer acetate with 898 similar patients who received no treatment. Participants were evaluated at least once with the Expanded Disability Status Scale (EDSS) after baseline. After a mean follow-up period of 7.12 years, individuals who had received glatiramer acetate showed a 16.5-percent reduction in disability progression and 25-percent reduction in loss of function, compared with the untreated group.16
Meanwhile, findings on the effects of DMTs on pregnancy and breast feeding suggest that neither glatiramer acetate nor interferon beta cause significant developmental delays in children who may have been exposed to either medication via breast milk. The researchers note that both interferon and glatiramer acetate are large molecules that are unlikely to enter breast milk, but that the specific effects on child development from using these diseasemodifying therapies during breast feeding have not been studied.
Drawing on information in a German pregnancy database, researchers reviewed data on 76 pregnancies in 72 women who had received either glatiramer acetate or interferon beta for MS. The mothers provided information on both their disease activity and their children’s development by completing a questionnaire after delivery. Forty-seven women stopped treatment during pregnancy and resumed treatment after delivery, and 18 women continued treatment through the entire pregnancy. At ages 1 and 2 years, the children’s body lengths were within normal ranges for their ages. Four percent of mothers reported that their children were experiencing developmental delays in motor skills, but the percentage was similar to the prevalence of early motor skill delays in the general population.46
Finally, an extended-release formulation of glatiramer acetate is under development. The experimental long-acting formulation, called “GA Depot,” consists of extended-release microspheres of glatiramer acetate released over approximately one month. GA Depot would be dosed once every 28 days, which researches hypothesize may improve patient adherence to the treatment regimen, and thus, may also improve outcomes.
Recently released Phase IIa data suggest that GA Depot is well tolerated and efficacious. Eleven individuals with RRMS who participated in a one-year core efficacy study of GA Depot also completed a 48-week extension study. The patients received GA Depot 40 mg once every 28 days during the extension. No adverse effects other than mild injection-site reactions were reported. Mean EDSS scores did not change significantly from the core-study baseline, and 81.8 percent of participants showed no evidence of disease activity (NEDA) when the extension study ended.47