plied the same inclusion criteria and included 251 patients treated for up to 35 months (Copaxone n=125, placebo n=126). The third study was a nine-month study involving 239 patients (Copaxone n=119, placebo n=120) where inclusion criteria were similar to those in the first and second studies with the additional criterion that patients had to have at least one gadolinium-enhancing lesion on the screening MRI.
In clinical trials in MS patients receiving Copaxone, a significant reduction in the number of relapses, compared with placebo, was seen.
In the largest controlled study, the relapse rate was reduced by 32% from 1.98 under placebo to 1.34 under glatiramer acetate.
Exposure data are available for up to twelve years in 103 patients treated with Copaxone.
Copaxone has also demonstrated beneficial effects over placebo on MRI parameters relevant to relapsing-remitting MS.
Copaxone had, however, no beneficial effect on progression of disability in relapsing-remitting MS patients.
There is no evidence that Copaxone treatment has an effect on relapse duration or severity.
There is currently no evidence for the use of Copaxone in patients with primary or secondary progressive disease.
Single clinical event suggestive of MS:
One placebo-controlled study involving 481 patients (Copaxone n=243, placebo n=238) was performed in patients with a well-defined, single, unifocal neurological manifestation and MRI features highly suggestive of MS (at least two cerebral lesions on the T2-weighted MRI above 6 mm diameter). Any disease other than multiple sclerosis that could better explain signs and symptoms of the patient had to be excluded.
During the placebo-controlled period of up to three years, Copaxone delayed the progression from the first clinical event to clinically definite multiple sclerosis (CDMS) according to Poser criteria in a statistically significant and clinically meaningful manner, corresponding to a risk reduction of 45% (Hazard Ratio = 0.55; 95% CI [0.40; 0.77], p-value=0.0005). The proportion of patients who converted to CDMS was 43% for the placebo group and 25% in the Copaxone group.
The favourable effect of treatment with Copaxone over placebo was also demonstrated in two secondary MRI endpoints, i.e. number of new T2 lesions and T2 lesion volume.
Post-hoc subgroup analyses were performed in patients with various baseline characteristics to identify a population at high risk to develop the second attack. For subjects with baseline MRI with at least one T1 Gd-enhancing lesion and 9 or more T2 lesions, conversion to CDMS was evident for 50% of the placebo subjects vs. 28% of the Copaxone subjects in 2.4 years. For subjects with 9 or more T2 lesions at baseline, conversion to CDMS was evident for 45% of the placebo subjects vs. 26% on Copaxone in 2.4 years. However, the impact of early treatment with Copaxone on the long term evolution of the disease is unknown even in these high-risk subgroups as the study was mainly designed to assess the time to the second event. In any case, treatment should only be considered for patients classified at high risk.
5.2 Pharmacokinetic properties
Pharmacokinetic studies in patients have not been performed. In vitro data and limited data from healthy volunteers indicate that with subcutaneous administration of glatiramer acetate, the active substance is readily absorbed and that a large part of the dose is rapidly degraded to smaller fragments already in subcu
