Teva Pharmaceuticals Industries Ltd. announced the publication of data that demonstrates significant differences in biological and immunological effects between Copaxone (glatiramer acetate, GA) and a purported generic glatiramer acetate (GA), marketed in India, (Glatiramer, Natco Pharma, Ltd., Hyderabad, India), with potential clinical ramifications.
The data, published in the online scientific journal PLOS ONE, are the results of gene expression analysis from mouse splenocytes (white blood cells found in the spleen) exposed to either Copaxone or the purported generic GA. The study demonstrated a predictable and therapeutically-aligned impact of Copaxone on genes associated with key immune response-related cells. This is in contrast to a significantly different and irregular impact on genes associated with these cells by the purported generic GA.
The cells identified in this study included regulatory T cells (Tregs), which control immune and auto-immune responses, and myeloid lineage cells- the precursors of many immune response cells. The gene expression impact and variability of the purported generic GA indicates different biological effects of these drugs.
“The data from this paper shows the possible significant ramifications of changes in physiochemical properties between Copaxone and a purported generic GA,” said Dr. Michael Hayden, president of global R&D and chief scientific officer for Teva Pharmaceutical Industries Ltd., and one of the study authors. “This study suggests a distinct potential difference in the impact of a purported generic GA on the immune system of patients, with possible implications on efficacy and safety in RRMS patients. Teva believes the only way to truly understand the impact of these differences is by conducting a full battery of clinical studies.”
The analysis found that Copaxone increases levels of FOXP3 more consistently and effectively than the purported generic GA. FOXP3 is a key factor controlling the development and function of Tregs, which may help suppress harmful autoimmunity in MS patients. Additional genes associated with these beneficial Tregs were also increased to a greater extent by Copaxone relative to the purported generic GA. The extent to which this differential impact on Tregs might affect patient response remains unknown.
The purported generic GA was also found to increase the expression of genes associated with myeloid lineage cells, such as monocytes and macrophages, to a greater extent than Copaxone. These cells play an important role in the immune systems of healthy people, but can also contribute to the worsening of RRMS. Without clinical trials, the extent to which the increased impact of the purported generic GA on myeloid lineage cells might alter clinical outcomes in RRMS patients remains unknown.
The study also shows that Copaxone has a more consistent biological impact across batches than the purported generic GA. A high degree of consistency was found across 34 samples from 30 different Copaxone batches. This compares with a high level of inconsistency across only 11 samples representing just five different batches of the purported generic GA.
“This extensive analysis indicates, in my view, a concerning lack of consistency and predictability in the purported generic GA’s effect on key elements of the murine immune system. Furthermore, variability seen in the expression of certain genes, from one batch of the purported generic GA to another, raises the possibility that patients may not receive the same treatment effect with each dose,” said Dr. Ben Zeskind, CEO, Immuneering Corporation, and co-author of the study.
Date: January 13, 2013
Filed Under: Drug Discovery