Synthon today announced that the company’s glatiramer acetate met the main endpoint of a late-stage study in patients with relapsing remitting multiple sclerosis (RRMS). The Phase III Glatiramer Acetate clinical trial To assess Equivalence with Copaxone®* (GATE) is to-date the only Phase III study conducted with a generic version of Copaxone® and has demonstrated an equivalent efficacy and safety profile for Synthon’s glatiramer acetate compared to Copaxone®.
GATE was set up following Scientific Advice received from the European Medicines Agency (EMA) with the aim to show equivalence of Synthon’s glatiramer acetate (Synthon GTR) with Teva’s Copaxone® in a well-controlled 3-arm double-blind study that was also designed to show superiority of the two active treatment groups over placebo. The large-scale, multicenter study consists of a nine-month double-blind efficacy comparison followed by a currently ongoing 15-month open-label extension and runs in Europe (including Russia, Ukraine and Belarus), Mexico, South Africa and the United States. “The data gathered during the double-blind part of the study present a solid basis for the regulatory submission in Europe in order to make an equivalent alternative to Copaxone® available to patients suffering from multiple sclerosis”, commented Jacques Lemmens, Synthon’s chief executive officer.
In the GATE study 796 patients with active RRMS were randomized to daily injections of Synthon’s glatiramer acetate (20 mg/ml), Copaxone® (20 mg/ml) or matching placebo for a double-blind 9-month treatment period. Primary endpoint of the study was the number of T1 gadolinium enhancing brain lesions on MRI assessed after 7, 8 and 9 months of treatment which were convincingly shown to be equally reduced in both the Synthon GTR as well as the Copaxone® treatment groups and significantly reduced compared to placebo. Other outcomes, including the incidence of MS relapses, disability, and patient reported tolerability, support the primary conclusion of the study. Safety analyses showed a comparable incidence of reported adverse reactions between both active glatiramer acetate groups.
Following the double-blind phase of the trial, patients in the Copaxone® and placebo groups of the GATE study switched over to Synthon GTR and are continuing Synthon GTR treatment for another 15-month period, as are the patients in the Synthon GTR arm of the study. This part of the study is expected to further confirm efficacy and safety of long-term Synthon GTR treatment as well as to provide evidence supporting the safety of switching therapies from Copaxone® to Synthon’s GTR.
Jeffrey Cohen, M.D., Professor in the Cleveland Clinic Lerner College of Medicine, Director of Experimental Therapeutics at the Cleveland Clinic Mellen MS Center, and Chair of the GATE Steering Committee, remarked that “these are important results. The mechanism of action of Copaxone® is not fully understood and the resulting complexity of developing a generic alternative/version is broadly acknowledged. Clinically proven equivalence will ensure that patients with multiple sclerosis are provided with an effective and safe alternative.”
Concludes Lemmens: “Glatiramer acetate is the first anticipated generic version of an approved MS product in the United States and the European Union. The future availability of a generic of Copaxone® means that MS treatments – which currently cost between USD 30,000-60,000 per patient per year – will become more affordable, thereby allowing more MS patients around the world to have access to this medication.”
Full details of the study will be submitted for publication in a peer-reviewed medical journal and presented at future scientific meetings.
Synthon has already submitted an Abbreviated New Drug Application (ANDA) for glatiramer acetate, 20 mg/ml solution for injection in pre-filled syringes to the United States FDA in November 2011.
* Copaxone® is a registered trademark of Teva Pharmaceutical Industries Ltd.
Synthon began the development of its generic version of Copaxone® in 2006 and filed an Abbreviated New Drug Application (ANDA) for the product with the FDA in November 2011. In parallel, it has conducted the GATE study for the purpose of seeking approval in the European Union.
The complexity of Copaxone® represents a significant challenge for generic companies to develop a similar version. The development challenge is compounded by the random alignment of the four amino acids in the polymer structure of the molecule. Due to this random alignment of the four amino acids, distinct peptide epitopes are formed. Although the mechanism of action of glatiramer has not yet been fully understood, growing evidence suggests that the presence of certain peptide epitopes is crucial for its clinical efficacy. Hence, the polymerization process should be optimally controlled to yield an epitope pattern that is similar to that of Copaxone®. The company used its expertise in the development of biologicals as well as small molecule development and manufacturing in order to develop a well characterized generic product.
Synthon’s glatiramer product shows similar detailed bio-analytical characterization test results to Copaxone® with respect to primary structure, higher order structure, physicochemical properties and biological activity. Synthon has produced multiple batches of drug substance and drug product used for development purposes and also for use in the clinical study. Therefore, the company is fully confident about the reproducibility of the manufacturing process. The therapeutic equivalence demonstrated in the GATE study using various batches of both GTR and Copaxone® further underlines that both products are similar from a CMC and clinical perspective. The company will produce the active pharmaceutical ingredient for its glatiramer acetate product in a dedicated, state-of-the-art large-scale manufacturing plant.
Synthon, with headquarters in Nijmegen, The Netherlands, is an international pharmaceutical company and a leader in the field of generic medicines. The company started its biopharmaceutical franchise in 2007 and is building a promising portfolio of next generation medicines. Synthon is developing rapidly into a specialty pharmaceutical company, focusing on the therapeutic areas of auto-immune diseases and oncology. Synthon products are currently approved by regulatory agencies in over 80 countries worldwide and marketed through strategic partnerships and – in dedicated areas – through direct sales. Synthon employs about 1,400 staff worldwide, and in 2013 it recorded a turnover of EUR 215 million. For more information, go to www.synthon.com.