US generics company Alvogen announced in September 2016 that it had launched a follow-on version of glatiramer acetate in Central and Eastern Europe. Then in November 2016, Russia’s Biocad announced that it had completed registration for its follow-on glatiramer acetate product in Russia.
The Alvogen product manufactured by Netherlands-based biologicals company Synthon  was determined by the competent authorities to be a therapeutically equivalent version of the originator medicine Copaxone, which is approved for the treatment of relapsing remitting multiple sclerosis (RRMS). Copaxone is classified as a non-biological complex drug (NBCD), but since there are currently no guidelines for ‘follow-on’ versions of NBCDs, such drugs are approved under the generics or hybrid pathways. However, due to their complexity and the fact that they cannot be fully quantitated, characterized or described by (physico)chemical analytical tools, some groups have said that the generics and hybrid pathways for these products may not be appropriate, and have called for regulatory guidelines for follow-on versions of NBCDs .
Glatiramer acetate (the active ingredient for Copaxone) is a complex mixture of synthetic polypeptides manufactured from four amino acids: alanine, lysine, glutamic acid, and tyrosine. It is produced entirely through chemical processes with standard starting materials in a tightly controlled and robust multiple stage manufacturing process. Due to its complexity, there is an inherent micro-heterogeneity between batches observed in both physicochemical and functional assays. The mechanism of action and the active components responsible for Copaxone’s clinical effect are still uncertain in spite of extensive research and a multitude of publications in peer-reviewed journals. Therefore, the entirety of the Copaxone constituents is considered to be the active pharmaceutical ingredient (API).
Alvogen’s follow-on glatiramer actetate product, called Remurel*, was launched with a proprietary auto-injector device (Autoxon), to help support MS patients in their treatment with Remurel. Remurel 20 mg was determined by the European health authorities to be therapeutically equivalent to daily Copaxone 20 mg, with similar active ingredients, route of administration, strength and dosage form. This approval was supported by a large-scale, multicentre, phase III study, known as GATE (Glatiramer Acetate clinical Trial to assess Equivalence to Copaxone). Results of the study served as basis for demonstration of equivalence in efficacy and safety necessary for approval. Teva’s Copaxone delivered sales of over Euros 510 million in Europe in 2015, according to IMS Midas data.
Biocad’s approval is based on two-year, phase III clinical study started in 2012, which, according to the company ‘proved its equivalence to the original drug, in terms of all indicators of efficacy and safety’. Follow-on versions of Copaxone are already produced in Russia by the local companies: F-Synthesis and R-Pharm and are purchased by the state as part of the existing ‘7 Diseases’ programme, which regulates state purchases of the most expensive drugs for state needs. According to the Russian Ministry of Health, the number of patients who regularly received glatiramer acetate was about 14,000 in 2015. The annual value of state purchases of glatiramer acetate is estimated at about 6.5 billion roubles.
The US Food and Drug Administration approved its first follow-on version of glatiramer acetate injection (Sandoz’s Glatopa) in April 2016 .
*The trade name for Synthon’s follow-on glatiramer actetate product varies from one EU country to another depending on the licensee.
EU guidelines for follow-on NBCDs
Follow-on glatiramer acetate (M365) claimed as equivalent to Copaxone
1. GaBI Online - Generics and Biosimilars Initiative. Follow-on glatiramer acetate gains European approval [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2017 Feb 24]. Available from: www.gabionline.net/Non-Biological-Complex-Drugs/News/Follow-on-glatiramer-acetate-gains-European-approval
2. GaBI Online - Generics and Biosimilars Initiative. Guidelines needed for follow-on versions of NBCDs [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2017 Feb 24]. Available from: www.gabionline.net/Reports/Guidelines-needed-for-follow-on-versions-of-NBCDs
3. GaBI Online - Generics and Biosimilars Initiative. FDA approves first follow-on version of glatiramer acetate [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2017 Feb 24]. Available from: www.gabionline.net/Non-Biological-Complex-Drugs/News/FDA-approves-first-follow-on-version-of-glatiramer-acetate
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