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Original Investigation | Clinical Trial

Equivalence of Generic Glatiramer Acetate in Multiple Sclerosis A Randomized Clinical Trial

Jeffrey Cohen, MD1; Anna Belova, MD2; Krzysztof Selmaj, MD3; Christian Wolf, MD4; Maria Pia Sormani, PhD5; Janine Oberyé, MSc6; Evelyn van den Tweel, PhD6; Roel Mulder6; Norbert Koper, PhD6; Gerrit Voortman, MSc6; Frederik Barkhof, MD7 ; for the Glatiramer Acetate Clinical Trial to Assess Equivalence With Copaxone (GATE) Study Group
[+] Author Affiliations
1Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, Ohio
2Functional Diagnostics, Research Institute of Traumatology and Orthopedics, Nizhniy Novgorod, Russian Federation
3Neurology Center Lodz, Lodz, Poland
4Lycalis sprl, Brussels, Belgium
5Department of Health Sciences, University of Genoa, Genoa, Italy
6Synthon BV, Nijmegen, the Netherlands
7Image Analysis Center, Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands
JAMA Neurol. 2015;72(12):1433-1441. doi:10.1001/jamaneurol.2015.2154.
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Importance  The patents for the first approved treatments for relapsing-remitting multiple sclerosis are expiring, creating the opportunity to develop generic alternatives.

Objective  To evaluate in the Glatiramer Acetate Clinical Trial to Assess Equivalence With Copaxone (GATE) study whether generic glatiramer acetate (hereafter generic drug) is equivalent to the originator brand glatiramer acetate (hereafter brand drug) product, as measured by imaging and clinical end points, safety, and tolerability.

Design, Setting, and Participants  Randomized, multicenter, double-blind, active and placebo-controlled phase 3 trial. The setting included academic medical centers and clinical practices. Participants were patients with relapsing-remitting multiple sclerosis 18 to 55 years old with at least 1 relapse in the prior year and 1 to 15 gadolinium-enhancing brain magnetic resonance imaging lesions. They were randomized between December 7, 2011, and March 21, 2013. The last participant completed follow-up December 2, 2013.

Interventions  Participants were randomized 4.3:4.3:1 to receive generic glatiramer acetate (20 mg), brand glatiramer acetate (20 mg), or placebo by daily subcutaneous injection for 9 months.

Main Outcomes and Measures  The primary end point was the total number of gadolinium-enhancing lesions during months 7, 8, and 9. Additional end points included other magnetic resonance imaging parameters, annualized relapse rate, and Expanded Disability Status Scale score. Safety and tolerability were assessed by monitoring adverse events, injection site reactions, and laboratory test results.

Results  In total, 794 participants were randomized and treated with generic drug (n = 353), brand drug (n = 357), or placebo (n = 84). The estimated mean numbers of gadolinium-enhancing lesions with generic drug and brand drug were lower than with placebo (ratio, 0.488; 95% CI, 0.365-0.651; P < .001), confirming study sensitivity. For gadolinium-enhancing lesions, the estimated ratio of generic drug to brand drug was 1.095 (95% CI, 0.883-1.360), which was within the predefined equivalence margin of 0.727 to 1.375. The incidence, spectrum, and severity of reported adverse events, including injection site reactions, were similar in the generic drug and brand drug groups.

Conclusions and Relevance  As treatment for relapsing-remitting multiple sclerosis, glatiramer acetate generic drug and brand drug had equivalent efficacy, safety, and tolerability.

Trial Registration  clinicaltrials.gov Identifier: NCT01489254

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Figure 1.
Consolidated Standards of Reporting Trials Diagram of Enrollment and Follow-up of Study Patients

aSome patients discontinued using the study drug and subsequently discontinued follow-up in the study.

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Figure 2.
Primary Study End Point (Full Analysis Set)

A, Data are the estimated means as calculated from the study sensitivity analysis that included all 3 treatment groups. B, To estimate the ratio of generic drug to brand drug, the analysis included the generic glatiramer acetate and brand glatiramer acetate treatment groups.aThe estimated mean number of new and persisting gadolinium-enhancing lesions during months 7 through 9 for the combined generic glatiramer acetate and brand glatiramer acetate treatment groups was 0.40.

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