NeuroTalk Support Groups - Double dose Copaxone more effective than single dose

Copaxone at double the dose appears to be about 40% more effective than regular dose Copaxone (on some measures, after 9 months), although we would all like to see how effective the higher dose is in slowing disability.

I believe the only thing that needs explaining is "For the 20th percentile, time to the first relapse was delayed from 80 days in the 20mg group to 213 days in the 40mg group." For example if there were 100 patients in each of the groups, with the patients ordered from "relapse in the fewest number of days" to "no relapses", the 20th patient in the 20 mg group would have had a relapse in 80 days, and the 20th in the 40 mg group had one after 213 days. (I think that's what it means.)

I think what Teva needs to do is develop a delivery system that makes Copaxone an alternative to liposuction. With double dose Copaxone, I would think lipoatrophy would be a more serious problem -- so I can see the advertising now -- "Target those hard-to-get areas with Copaxone!"

Randomised, double-blind, parallel-group, dose-comparison study of glatiramer acetate in relapsing-remitting multiple sclerosis

J. Cohen, M. Rovaris, A. Goodman, D. Wynn, D. Ladkani, M. Filippi for the 9006 Study Group

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Background: Three pivotal trials support the safety, tolerability, and efficacy of Copaxone (glatiramer acetate; GA) 20mg/day by subcutaneous injection in relapsing-remitting multiple sclerosis (MS). There are few data concerning other doses.

Objective: This nine-month multi-center, randomized, double-blind, parallel-group, Phase II study evaluated the safety, tolerability, and efficacy of GA 40mg compared to the currently-approved 20mg dose.

Methods: Eligibility criteria included clinically-definite MS with a relapse in the prior year, Expanded Disability Status Scale score 0-5.0, no prior use of GA, and 1-15 gadolinium-enhancing (GdE) lesions on a screening MRI (which also served as the pre-treatment baseline MRI). Subjects then underwent MRI at months 3, 7, 8 and 9, and neurological assessments at baseline then months 3, 6, and 9.

Results: Of 229 subjects screened, 90 were randomized to GA 20mg (n=44) or 40mg (n=46). The groups were well-matched at baseline on demographic, clinical, and MRI characteristics.

The primary efficacy endpoint, total GdE lesion number at months 7, 8, and 9, showed a 38% greater reduction favoring 40mg (relative risk=0.62; 95% CI=0.36-1.08; p=0.0898) with mean lesions per scan (SD) equal to 0.79 (1.36) for the 40mg group versus 1.32 (1.51) for the 20mg group.

A difference emerged as early as month 3, 1.33 (1.58) lesions for the 40mg group versus 2.61 (4.22) lesions for the 20mg group (52% reduction; p=0.0051). There was a trend favoring 40mg for relapse rate with significant benefit on proportion of relapse-free subjects (p=0.0183) and time to first relapse (p=0.0367).

For the 20th percentile, time to the first relapse was delayed from 80 days in the 20mg group to 213 days in the 40mg group. The proportion of patients being both relapse-free, and free of GdE lesions at months 7, 8, and 9 (or with the mean number of GdE lesions reduced by 50% or more versus baseline), was higher for the 40mg group (69% versus 38.5%, Odds-Ratio=3.52 [1.39-8.88], p=0.0078).

GA 40mg was well-tolerated with a safety profile similar to the 20mg dose. Injection site reactions and immediate post-injection reactions were somewhat more common and severe with the higher dose.

Conclusions: This study demonstrated that GA 40mg is safe and well-tolerated. The overall efficacy results provided evidence that the 40mg dose of GA may be more effective than the currently approved 20mg dose in reducing MRI activity and clinical relapses.