Momenta Pharmaceuticals, Inc. (MNTA)

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[Synthon] Generic Glatiramer Matches Branded Copaxone in Clinical Efficacy
- But don't expect a break from the high annual cost

http://www.medpagetoday.com/Neurology/MultipleSclerosis/54098

A generic version of glatiramer acetate produced by the Dutch firm Synthon showed equivalent efficacy, safety, and tolerability as Copaxone, the original branded drug, in a randomized trial among patients with relapsing-remitting multiple sclerosis (RRMS).

Over a period of 9 months, the incidence, spectrum, and severity of reported adverse events, including injection site reactions, were similar in both the generic drug and brand drug groups, Jeffrey Cohen, MD, of the Cleveland Clinic, Cleveland, OH, and colleagues reported online in JAMA Neurology. (Some of the results had been reported in a 2014 conference presentation, but certain results were slightly different in the journal publication which also included more detail.)

The Glatiramer Acetate Clinical Trial to Assess Equivalence With Copaxone (GATE) study showed that the generic drug was effective and reduced gadolinium-enhancing lesions in RRMS to the same extent as the brand-name drug. And while equivalence margins for other magnetic resonance imaging (MRI) and clinical end points were not defined, the 95% confidence intervals (CIs) for the generic drug and brand drug groups substantially overlapped, said the investigators.

"The GATE study, to our knowledge, is the first phase III clinical trial to date of a generic disease-modifying medication for MS," they wrote. "These results may allow for a generic alternative to the originator brand glatiramer acetate, an RRMS treatment with established long-term efficacy and safety."

GATE used an equivalence design (as opposed to non-inferiority) to meet requirements for clinical trial assessment of efficacy, safety, and tolerability as regulated by the European Medicines Agency.

The FDA recently approved another generic glatiramer acetate drug made by Sandoz on the basis of the standard bioequivalency testing the agency uses in approving generics. The Synthon product has not yet been approved in the U.S.; its marketing application is still under review.

In GATE, 794 RRMS patients from 118 academic medical centers and clinical practices in 17 countries were randomized at a roughly 4:4:1 ratio to receive the generic product, the branded drug, and placebo, respectively, for 9 months.

Participants were 18 to 55 years of age and had experienced at least one relapse in the prior year, as well as from one to 15 gadolinium-enhancing lesions.

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 (EDSS) score.

Adverse events, injection site reactions, and laboratory test results were monitored to assess safety and tolerability.

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, reported Cohen and colleagues. 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 estimated annualized relapse rates were 0.31 (95% CI 0.20-0.48) for generic drug, 0.40 (95% CI 0.26-0.62) for brand drug, and 0.38 (95% CI 0.22-0.66) for placebo.

The percentages of participants confirmed relapse-free were:
79.3% for the generic
73.9% for Copaxone
73.8% for placebo

Mean EDSS scores were stable in the three treatment groups, Cohen and colleagues reported, and included 9.3% in the generic drug group, 9.2% in the brand drug group, and 7.1% in the placebo group.

Adverse effects were similar between the two versions and nothing unexpected was seen.

This study provides "reassurance that a properly manufactured generic glatiramer acetate can have efficacy similar to that of branded glatiramer acetate," Dennis Bourdette, MD, FAAN, and Daniel Hartung, DPharm, MPH, commented in an accompanying editorial.

"Based on the available evidence, neurologists who prescribe glatiramer acetate at a dose of 20 mg subcutaneously once a day should have confidence that FDA- and EMA-approved glatiramer acetate generics will be as efficacious and safe as branded glatiramer acetate," wrote Bourdette and Hartung, who are both with Oregon Health & Science University in Portland.

But in a commentary Bourdette and Hartung wrote for Neurology earlier this year with two colleagues, they cautioned that introduction of generic glatiramer acetate products may not do much to contain the high costs of MS drugs.

They noted that the actual cost for Sandoz's generic glatiramer acetate is estimated to be $63,000 a year. "This is just $11,000 less than branded glatiramer acetate ... and only $2,000 less annually than a new [less frequently dosed] branded glatiramer acetate," they wrote in the Neurology commentary.


The GATE study was funded by Synthon BV.

The authors disclosed relationships with Synthon BV, EMD Serono, Genentech, Genzyme, Innate Immunotherapeutics, Vaccinex, Roche, Biogen Idec, Novartis, Teva, Merck, Receptos, Neuron, BBB Therapeutics BV, Desitin GmbH, Bayer Schering Pharma, Sanofi Aventis, Biogen Idec, Novartis, and Jansen Research.

Cohen also disclosed that he is a co- editor of Multiple Sclerosis Journal – Experimental, Translational and Clinical.