Contributions
Abstract: P1170
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: ALKS 8700 is a prodrug of monomethyl fumarate (MMF) that is rapidly converted to MMF, the active metabolite of dimethyl fumarate (DMF). Oral DMF was approved for relapsing forms of multiple sclerosis (MS) based on Phase 3 efficacy data. In Phase 3 DMF studies, gastrointestinal (GI) adverse events (AEs) were the leading cause of study discontinuation due to AEs. ALKS 8700 was associated with a low GI AE rate when administered to healthy subjects in Phase 1 studies. ALKS 8700 has physicochemical properties that are distinct from DMF and was designed to effectively treat relapsing forms of MS in a manner similar to DMF but with the potential for improved GI tolerability.
Objective: ALKS 8700 is being developed as an oral disease-modifying treatment for relapsing forms of MS. EVOLVE-MS-1 evaluates the long-term safety and treatment effect of ALKS 8700 in patients with relapsing-remitting MS (RRMS).
Methods: EVOLVE-MS-1 is a global, interventional, open-label, Phase 3 study evaluating long-term safety of ALKS 8700 (462 mg twice daily) in ~930 patients with RRMS (ClinicalTrials.gov: NCT02634307). Main inclusion criteria: patients (18-65 years) with diagnosis of RRMS (2010 revised McDonald criteria), Expanded Disability Status Scale (EDSS) score ≤ 6.0, and no evidence of relapse within 30 days of study start. Main exclusion criteria: diagnosis of a progressive form of MS and history of other clinically significant disease. De novo patients and patients continuing from eligible ALKS 8700 studies will be enrolled for up to 96 weeks. Assessments include clinical relapses, AEs, laboratory tests, vital signs, electrocardiograms, and MRI imaging.
Results: EVOLVE-MS-1 is planned or ongoing in 10 countries. As of March 3, 2017, 543 patients have been enrolled. Among the patients enrolled, the median age is 41.0 years (range 18-65), and the majority are female (72.4%) and white (92.1%). Mean time since onset of MS is 9.0 years (median 8.0, range 0-41) and 72% of patients have received prior MS treatment. The mean baseline EDSS is 2.66 (median 2.5, range 0.0-6.0). A study update as of September 2017 will be presented, including patient demographics, baseline characteristics, and study discontinuation rates due to GI-related AEs within 1 month of treatment initiation.
Conclusions: Results from this long-term study over a treatment period of 96 weeks will provide valuable insight into the safety and tolerability of ALKS 8700 (462 mg twice daily) in patients with RRMS.
Disclosure:
RTN has consulted for Acorda, Alkermes, Bayer, Biogen, EMD Serono, Genentech, Genzyme, Mallinckrodt, Novartis, and Pfizer and was on the speaker bureau for Acorda, Biogen, and Genzyme.
RALP, DR, TG, and LvM are employees and stockholders in Alkermes, Inc.
JSW has served on advisory boards, data monitoring or steering committees, has consulting agreements, or received speaker honoraria from the following entities: AbbVie, AcademicCME, ACTRIMS, Alkermes, Bayer HealthCare, Biogen, Bionest, Celgene, Clene Nanomedicine, CMSC, ECTRIMS, Forward Pharma A/S, Medday Pharmaceuticals, Novartis Pharmaceuticals, PRIME, Roche Genentech, Sanofi Genzyme, Strategic Consultants International, Takeda, Teva Pharmaceuticals, WebMD; royalties are received for out licensed monoclonal antibodies through UTHealth from Millipore Corporation. This study is sponsored by Alkermes, Inc., Waltham, MA, USA.
Abstract: P1170
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: ALKS 8700 is a prodrug of monomethyl fumarate (MMF) that is rapidly converted to MMF, the active metabolite of dimethyl fumarate (DMF). Oral DMF was approved for relapsing forms of multiple sclerosis (MS) based on Phase 3 efficacy data. In Phase 3 DMF studies, gastrointestinal (GI) adverse events (AEs) were the leading cause of study discontinuation due to AEs. ALKS 8700 was associated with a low GI AE rate when administered to healthy subjects in Phase 1 studies. ALKS 8700 has physicochemical properties that are distinct from DMF and was designed to effectively treat relapsing forms of MS in a manner similar to DMF but with the potential for improved GI tolerability.
Objective: ALKS 8700 is being developed as an oral disease-modifying treatment for relapsing forms of MS. EVOLVE-MS-1 evaluates the long-term safety and treatment effect of ALKS 8700 in patients with relapsing-remitting MS (RRMS).
Methods: EVOLVE-MS-1 is a global, interventional, open-label, Phase 3 study evaluating long-term safety of ALKS 8700 (462 mg twice daily) in ~930 patients with RRMS (ClinicalTrials.gov: NCT02634307). Main inclusion criteria: patients (18-65 years) with diagnosis of RRMS (2010 revised McDonald criteria), Expanded Disability Status Scale (EDSS) score ≤ 6.0, and no evidence of relapse within 30 days of study start. Main exclusion criteria: diagnosis of a progressive form of MS and history of other clinically significant disease. De novo patients and patients continuing from eligible ALKS 8700 studies will be enrolled for up to 96 weeks. Assessments include clinical relapses, AEs, laboratory tests, vital signs, electrocardiograms, and MRI imaging.
Results: EVOLVE-MS-1 is planned or ongoing in 10 countries. As of March 3, 2017, 543 patients have been enrolled. Among the patients enrolled, the median age is 41.0 years (range 18-65), and the majority are female (72.4%) and white (92.1%). Mean time since onset of MS is 9.0 years (median 8.0, range 0-41) and 72% of patients have received prior MS treatment. The mean baseline EDSS is 2.66 (median 2.5, range 0.0-6.0). A study update as of September 2017 will be presented, including patient demographics, baseline characteristics, and study discontinuation rates due to GI-related AEs within 1 month of treatment initiation.
Conclusions: Results from this long-term study over a treatment period of 96 weeks will provide valuable insight into the safety and tolerability of ALKS 8700 (462 mg twice daily) in patients with RRMS.
Disclosure:
RTN has consulted for Acorda, Alkermes, Bayer, Biogen, EMD Serono, Genentech, Genzyme, Mallinckrodt, Novartis, and Pfizer and was on the speaker bureau for Acorda, Biogen, and Genzyme.
RALP, DR, TG, and LvM are employees and stockholders in Alkermes, Inc.
JSW has served on advisory boards, data monitoring or steering committees, has consulting agreements, or received speaker honoraria from the following entities: AbbVie, AcademicCME, ACTRIMS, Alkermes, Bayer HealthCare, Biogen, Bionest, Celgene, Clene Nanomedicine, CMSC, ECTRIMS, Forward Pharma A/S, Medday Pharmaceuticals, Novartis Pharmaceuticals, PRIME, Roche Genentech, Sanofi Genzyme, Strategic Consultants International, Takeda, Teva Pharmaceuticals, WebMD; royalties are received for out licensed monoclonal antibodies through UTHealth from Millipore Corporation. This study is sponsored by Alkermes, Inc., Waltham, MA, USA.