EVOLVE-MS-2: Randomized, Double-blind Phase 3 Study of Gastrointestinal Tolerability for ALKS 8700 Versus Dimethyl Fumarate in Relapsing-Remitting Multiple Sclerosis

Background: ALKS 8700 is being developed as an oral disease-modifying treatment for relapsing forms of multiple sclerosis (MS). ALKS 8700, an aminoethyl ester of monomethyl fumarate (MMF), is rapidly converted to MMF, the active metabolite of dimethyl fumarate (DMF). Oral DMF is approved for the treatment of relapsing forms of MS based on Phase 3 efficacy data; however, gastrointestinal (GI) adverse events (AEs) were among the most commonly reported AEs and the leading cause of study discontinuation due to AEs. Subsequent DMF clinical studies using GI symptom questionnaires reported even greater rates of GI events and discontinuations, perhaps reflective of real-world patient experience. GI events are an important concern for patients taking DMF and can negatively impact treatment adherence, ultimately leading to treatment discontinuation. ALKS 8700 was designed to treat relapsing forms of MS with the potential for improved GI tolerability.

Objectives: EVOLVE-MS-2 evaluates the safety and GI tolerability of ALKS 8700 and DMF in patients with relapsing-remitting MS (RRMS).

Methods: In this double-blind, Phase 3 study (EVOLVE-MS-2), approximately 420 patients with RRMS will be randomized 1:1 to oral treatment with ALKS 8700 462 mg (twice daily) or DMF 240 mg (twice daily) for 5 weeks. GI tolerability will be assessed using daily GI symptom and functional impact questionnaires. Key inclusion criteria: patients aged 18-65 years with confirmed diagnosis of RRMS (2010 revised McDonald criteria), Expanded Disability Status Scale score ≤6.0, and no evidence of relapse within 30 days before study start. Key exclusion criteria: diagnosis of progressive forms of MS, prior treatment with DMF, pregnancy, or history of other clinically significant disease. Primary and secondary endpoints will be based on the GI symptom and functional impact questionnaires. Safety will be assessed via AE reporting and standard clinical, laboratory, and imaging measures. Patients completing this study will be eligible to participate in the ongoing open-label, long-term safety study (EVOLVE-MS-1, ClinicalTrials.gov: NCT02634307).

Results: This study is expected to begin enrollment in March 2017 and will include patients across multiple sites in the United States.

Conclusions: Results from this randomized, double-blind study will evaluate the GI tolerability of ALKS 8700 compared with DMF in patients with RRMS.