Physicochemical and Biological Characterization of both Copaxone and the European Follow-On Glatiramer Acetate Product (P1.400)

Objective: Copaxone release methods and additional physicochemical and biological assays were employed to evaluate compositional and functional characteristics of FOGA in Synthon EU product relative to GA in Copaxone. Background: Copaxone (glatiramer acetate, Teva), has provided a safe and effective treatment option for multiple sclerosis for 20+ years. In April 2016, a follow-on glatiramer acetate product (FOGA, Synthon) was approved in the EU. Design/Methods: Physicochemical (PCC) methods: molecular weight distribution (MWD), Coomassie Brilliant Blue G-250 (CBBG), Viscotek, cation exchange chromatography (CEX), Atomic Force microscopy (AFM), 2D-RPLC MALLS; Biological assays: cell-based potency, cytotoxicity, and monoclonal and polyclonal antibody bio-recognition; Genomic profiling: THP-1 cells and ex-vivo activated mouse splenocytes immunized with Copaxone or FOGA. Results: FOGA lots (n = 6) were within Copaxone specification, typical distribution or micro-heterogeneity range of random Copaxone lots for 6 of 14 PCC and bio-recognition methods used. Consistent differences in attributes of surface charge distribution and compositional parameters of molecular and spatial size were observed in CEX and Viscotek tests. The average Synthon MWD value at peak max was significantly higher than simulated Copaxone MWD peak values (n=957; p in vitro cytotoxicity activity; and FOGA lots showing significantly higher average potency compared to simulated Copaxone values (p Conclusions: Consistent differences were observed in compositional and functional characteristics of FOGA in Synthon’s EU FOGA product. Altered surface charge distribution, associated in literature with cytotoxicity and immune alterations (Frolich et al. 2012; Bhattacharjee et al. 2010; Fromen et al. 2016), was observed for the EU FOGA. Study Supported by: Teva Pharmaceutical Industries Disclosure: Dr. Timan has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Teva Pharmaceutical Industries. Dr. Komlosh has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Teva Pharmaceutical Industries. Dr. Beriozkin has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Teva Pharmaceutical Industries. Dr. Konya has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Teva Pharmaceutical Industries. Dr. Wells-Knecht has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Teva Pharmaceutical Industries. Dr. Weinstein has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Teva Pharmaceutical Industries. Dr. Sahly has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Teva Pharmaceutical Industries. Dr. Gilbert has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Teva Pharmaceutical Industries. Dr. Bar-Ilan has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Teva Pharmaceutical Industries. Dr. Zhang has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Immuneering. Dr. Funt has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Immuneering. Dr. Hasson has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Teva Pharmaceutical Industries. Dr. Laifenfeld has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Teva Pharmaceutical Industries. Dr. Kolitz has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Immuneering. Dr. Zeskind has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Immuneering. Dr. Melamed-Gal has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Teva. Dr. Loupe has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Teva Pharmaceutical Industries. Dr. Grossman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Teva Pharmaceutical Industries. Dr. Laufer has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Teva Pharmaceutical Industries. Dr. Hayden has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Teva Pharmaceutical Industries.