Alkermes will showcase its work in developing a treatment that harnesses the effect of Tecfidera (dimethyl fumarate) for relapsing multiple sclerosis (MS), while lowering the risk of stomach problems at the 7th Joint ECTRIMS-ACTRIMS Meeting this month in Paris.
The investigational drug, ALKS 8700, uses the same mechanism of action as Tecfidera. By building the molecule in a different way, however, the company expects it will show better tolerability.
Once in the body, dimethyl fumarate turns into monomethyl fumarate (MMF), the molecule that actually impacts MS disease processes. But before giving rise to MMF, dimethyl can cause side effects in users, particularly gastrointestinal. In fact, stomach problem were what caused people in Tecfidera Phase 3 trials to stop the treatment.
Alkermes uses a so-called prodrug approach to try to overcome this problem. By attaching a different compound to MMF — which breaks away from the molecule once in the body — it is possible to deliver MMF with lesser gastrointestinal side effects, Phase 1 study data indicate.
“We designed ALKS 8700, an MMF prodrug with distinct physical-chemical properties, to harness the efficacy of monomethyl fumarate with a differentiated safety and tolerability profile,” Elliot Ehrich, MD, executive vice president of research and development at Alkermes, said in a press release.
At the meeting, the company will present two posters on two clinical trials exploring ALKS 8700 in patients with relapsing-remitting MS.
The first presentation, “EVOLVE-MS-2: A Randomized, Double-Blind, Phase 3 Study of the Gastrointestinal Tolerability of ALKS 8700 Versus Dimethyl Fumarate in Relapsing-Remitting Multiple Sclerosis,” will describe a Phase 3 trial (NCT03093324) that aims to compare ALKS 8700 to Tecfidera in about 420 patients. (This study, set to end in February 2019, is currently recruiting RRMS patients at sites across the U.S.)
The trial is primarily concerned with the drug’s safety, and will measure the occurrence and impact of gastrointestinal side effects in the two treatment groups. The presentation will only include descriptions of patients characteristics and study design, as outcomes are yet to be analyzed.
Patients who complete the Phase 3 trial will be eligible to continue in an ongoing open-label, long-term safety study, called EVOLVE-MS-1 (NCT02634307), covered in the company’s second presentation, “EVOLVE-MS-1: A Phase 3, Open-Label, Long-Term Safety Study of ALKS 8700 in Relapsing-Remitting Multiple Sclerosis.”
By March 3, 2017, the study had enrolled 543 patients. In addition to describing patient characteristics, researchers will present the rates of discontinuation caused by gastrointestinal adverse events within one month of starting the treatment. (The open-label study is also recruiting at sites across the U.S. and Europe; information is available via its clinical trial number.)
“The presentations at MSParis2017 will provide additional insight into the emerging safety and tolerability profile of ALKS 8700 and the potential of ALKS 8700 to provide patients suffering from MS with an important treatment alternative,” Ehrich concluded.