title: Equivalence of Generic Glatiramer Acetate in Multiple Sclerosis: A Randomized Clinical Trial.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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
  As treatment for relapsing-remitting multiple sclerosis, glatiramer acetate generic drug and brand drug had equivalent efficacy, safety, and tolerability.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01489254.
authors.affiliation: Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Cohen
authors.affiliation: Functional Diagnostics, Research Institute of Traumatology and Orthopedics, Nizhniy Novgorod, Russian Federation.
authors.forename: Anna
authors.initials: A
authors.lastname: Belova
authors.affiliation: Neurology Center Lodz, Lodz, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Selmaj
authors.affiliation: Lycalis sprl, Brussels, Belgium.
authors.forename: Christian
authors.initials: C
authors.lastname: Wolf
authors.affiliation: Department of Health Sciences, University of Genoa, Genoa, Italy.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Sormani
authors.affiliation: Synthon BV, Nijmegen, the Netherlands.
authors.forename: Janine
authors.initials: J
authors.lastname: Oberyé
authors.affiliation: Synthon BV, Nijmegen, the Netherlands.
authors.forename: Evelyn
authors.initials: E
authors.lastname: van den Tweel
authors.affiliation: Synthon BV, Nijmegen, the Netherlands.
authors.forename: Roel
authors.initials: R
authors.lastname: Mulder
authors.affiliation: Synthon BV, Nijmegen, the Netherlands.
authors.forename: Norbert
authors.initials: N
authors.lastname: Koper
authors.affiliation: Synthon BV, Nijmegen, the Netherlands.
authors.forename: Gerrit
authors.initials: G
authors.lastname: Voortman
authors.affiliation: Image Analysis Center, Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
mesh_terms: D000293:Adolescent; D000328:Adult; D004185:Disability Evaluation; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D000068717:Glatiramer Acetate / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy*; D013810:Therapeutic Equivalency; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D000068717:Glatiramer Acetate