ALKS 8700 is known to activate a protein called Nrf2 which is thought to have antioxidant properties and has the ability to reduce oxidative stress. Oxidative stress can damage mitochondria (the powerhouses of all cells within our body) and ultimately cause the nerve cells to degenerate. ALKS 8700 is also a prodrug, meaning that it is metabolized into an active agent, called monomethyl fumarate, once it's inside the body.
ALKS 8700 is similar to the active agent found in Biogen’s commercially available drug called Tecfidera (dimethyl fumarate) but with the potential for improved gastrointestinal tolerability.
Phase III Trial: EVOLVE-MS-1
EVOLVE-MS-1 is a phase III, multicenter, open-label clinical trial will examine the safety, efficacy, and tolerability of oral ALKS 8700 (462 mg twice daily) in 935 adults with RRMS over 96-weeks. Interim results were presented at the 2018 American Academy of Neurology Annual Meeting. The annualized relapse rate in 570 participants after one year of treatment was 0.16. Furthermore, in a subset of these individuals, MRI analysis showed a significant reduction in the number of gadolinium-enhancing lesions and T1 and T2 lesions compared to when participants first joined the trial. The trial is still recruiting participants and is expected to be completed in 2020.
Phase III Trial: EVOLVE-MS-2
EVOLVE-MS-2 is a phase III, randomized, multicenter clinical trial evaluating the tolerability of ALKS 8700 (462 mg twice daily) compared to dimethyl fumarate (240 mg twice daily). The trial is recruiting 420 participants that will be administered either ALKS 8700 or dimethyl fumarate for five weeks. The primary outcome will measure the number of days that participants experience gastrointestinal side effects. Secondary measures will include other potential side effects. The study is still recruiting and expected to be completed in 2019.
In a phase I, randomized, double-blind clinical trial, which assessed the safety, tolerability, and pharmacokinetics of a single dose of ALKS 8700 or dimethyl fumarate in 35 healthy participants showed that the most common adverse effects were flushing, dizziness, and constipation for ALKS 8700 compared to flushing, nausea, and diarrhea for dimethyl fumarate.
Naismith R et al. EVOLVE-MS-1: A Phase 3, Open-Label, Long-Term Safety Study of ALKS 8700 in Relapsing-Remitting Multiple Sclerosis (P6.360). Neurology (Meeting Abstract), April 9, 2018.