Letter to the Editor Regarding: A Comprehensive Review on Copemyl^®

Excerpt

We read the review by Annovazzi et al. [1] with great interest. Glatiramer acetate (GA) after the approval of various regulatory agencies has been reliably used for over two decades as first-line treatment for relapsing forms of multiple sclerosis (MS) based on consistent results of multiple clinical trials [2‐5] establishing broad consensus among general neurologists and MS experts. Assessment of the published preclinical and clinical data of Copemyl^® (Mylan N.V., Hatfield, UK), a new member of the follow-on glatiramer acetate (FoGA) class, which include some aspects of its biological and immunological properties, as well as results from the randomized controlled trial that resulted in its authorization, is thus of scientific and medical interest. In their recent review article, Annovazzi et al. reported the published information and marketing authorization decision on Copemyl^® [1]. The authors raised questions about some drawbacks and limitations of the GATE (Glatiramer Acetate Clinical Trial to Assess Equivalence with Copaxone) study and its open-label extension [6, 7], the most relevant one being the discrepancy between clinical and magnetic resonance (MRI) end points during the double-blind phase of the study, which invalidates the fundamental study design hypothesis and does not comply with EMA (European Medicines Agency) guidelines [8]. However, several additional gaps and inaccuracies were not included in Annovazzi’s review and should be presented to physicians and the scientific community for further resolution in the interest of public health. These are particularly relevant for country-specific decisions on the substitutability of Copaxone^® (Teva Pharmaceutical Industries, Petach Tiqva, Israel) with a FoGA, given the concerns for immunogenic risk to individual patients. The EMA stated that GA is neither a small molecule nor a biologic drug but is rather a non-biologic complex drug (NBCD) comprised of up to 10²⁹ polypeptides, sub-sequences of which being antigens that modulate the immune system driving T cell differentiation towards immune tolerant T regulatory (T_reg) cells at the expense of autoreactive T helper (Th)1 and Th17 cells. …