EVOLVE-MS-1: A Phase 3, Open-Label, Long-Term Safety Study of ALKS 8700 in Relapsing-Remitting Multiple Sclerosis (P6.360)

Objective: ALKS 8700 (also known as BIIB098) is an investigational oral treatment for relapsing forms of MS. The ongoing EVOLVE-MS-1 study evaluates long-term safety and efficacy of ALKS 8700 in relapsing-remitting MS (RRMS) patients. Interim baseline and safety data are presented.

Background: ALKS 8700, a monomethyl fumarate (MMF) prodrug, is rapidly converted to MMF. MMF is the active metabolite of dimethyl fumarate (DMF), an approved oral treatment for MS. Gastrointestinal (GI) adverse events (AEs) and GI-related treatment discontinuation have been associated with DMF. ALKS 8700 has physicochemical properties, including solubility, that are distinct from DMF, and has the potential for improved GI tolerability.

Design/Methods EVOLVE-MS-1 evaluates ALKS 8700 (462 mg twice daily) for up to 96 weeks in RRMS patients. Main inclusion criteria: 18–65 years, RRMS (2010 revised McDonald criteria), EDSS ≤6.0, no evidence of relapse ≤30 days of study start.

Results: By September 4, 2017, 582 patients were enrolled: mean age 41.4 years (standard deviation [SD] 10.96); 72.0% female; 91.4% white. Mean time since MS onset was 9.5 years (SD 7.93) and 73.0% received prior MS treatment. Mean baseline EDSS score was 2.68 (SD 1.44). During the first month of treatment, three patients (0.5%) discontinued due to GI AEs; there were no serious GI AEs. Serious AE and AE-related discontinuation rates were 2.3% and 3.7% for months 0–3.

Conclusions: Safety data from the first 3 months of EVOLVE-MS-1 showed that treatment with ALKS 8700 was associated with low rates of GI AEs leading to discontinuation (0.5%) and no occurrence of serious GI AEs. Serious AE and AE-related discontinuation rates in months 0–3 were also low. Although data are limited, ALKS 8700 is associated with high rates of treatment persistence within the first 3 months of initiation, and thereby demonstrates the potential to be an oral therapeutic option for patients with RRMS.

Study Supported by:

This study is sponsored by Alkermes, Inc. (Waltham, MA, USA) and Biogen (Cambridge, MA, USA).

Disclosure: Dr. Naismith has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Acorda, Alkermes, Bayer, Biogen, EMD Serono, Genentech, Genzyme, Novartis, Teva.. Dr. Leigh-Pemberton has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alkermes. Dr. Rezendes has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alkermes. Dr. Nangia has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alkermes. Dr. Nangia has received compensation for serving on the Board of Directors of Alkermes. Dr. Kandinov has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alkermes. Dr. von Moltke has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alkermes. Dr. Wolinsky has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with has served on advisory boards and data monitoring or steering committees, has held consulting agreements or has received speaker honoraria from AbbVie, Alkermes, Biogen, Bionest, Clene Nanomedicine, EMD Serono, Forward Pharma, MedDay, Pharmaceuticals, Nov. Dr. Wolinsky has received royalty, license fees, or contractual rights payments from royalties for monoclonal antibodies out-licensed to Chemicon International through UTHealth.