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– ALKS 8700, a novel prodrug of monomethyl fumarate, looks promising as an oral, disease-modifying treatment for relapsing forms of multiple sclerosis, according to interim findings from the phase 3 EVOLVE-MS-1 study.

The annualized relapse rate at a median follow-up of 0.93 patient-years (total, 497.1 patient-years) in 578 patients enrolled to date in the 2-year, open-label study was just 0.16, Robert T. Naismith, MD, reported during an emerging science session at the annual meeting of the American Academy of Neurology.

Further, a statistically significant 80% reduction from baseline was seen in the number of gadolinium-enhancing lesions in 374 patients who completed a 1-year MRI assessment (from a mean of 1.5 to 0.3), said Dr. Naismith of Washington University, St. Louis.

Patients enrolled in the ongoing study are adults aged 18-65 years (mean, 41 years) with confirmed relapsing-remitting MS (RRMS), Expanded Disability Status Scale score of 6.0 or less (mean, 2.7), and no evidence of relapse within 30 days prior to starting ALKS 8700. Those with progressive forms of MS are excluded, as are patients who are pregnant or breastfeeding, patients with a history of other clinically significant conditions, and those with clinically significant abnormal laboratory tests at screening or absolute lymphocyte counts less than 0.9 x 103/mcL.

Of those enrolled so far, 72.5% received prior MS therapies, and their mean time since onset and diagnosis of MS was 9.7 and 7.6 years, respectively. The mean number of relapses in the prior year was 0.8.

ALKS 8700, also known as BIIB098, is given at a dose of 462 mg twice daily for up to 96 weeks; planned enrollment in EVOLVE-MS-1 is approximately 900 patients, Dr. Naismith said.

The preliminary findings from EVOLE-MS-1, which is limited by its single-arm, open-label design, “lend credence to ALKS 8700 as an oral treatment for patients with relapsing-remitting MS,” he said.

 

 


In addition to continued evaluation for long-term safety and tolerability in the current study, ALKS 8700 is also being evaluated in combination with 240 mg of twice daily dimethyl fumarate (DMF; Tecfidera) in the 5-week, randomized, double-blind EVOLVE-MS-2 study, which is looking at the gastrointestinal tolerability of the combination in patients with RRMS.

Oral DMF is approved for RRMS, and has been shown to significantly reduce clinical and MRI disease activity, but is commonly associated with GI events. Monomethyl fumarate is the active metabolite of DMF, and as a prodrug of monomethyl fumarate, ALKS 8700 is being developed to work in a manner similar to that of DMF, but with improved GI tolerability, Dr. Naismith explained.

EVOLE-MS-1 is funded by Alkermes. Dr. Naismith has served as a consultant and/or speaker for Alkermes, as well as for Acorda, Bayer, Biogen, Genentech, Genzyme, EMD Serono, Novartis, and Teva. He has received research support from the National Institutes of Health and the National Multiple Sclerosis Society.

SOURCE: Naismith R et al. AAN 2018 Emerging Science Abstract 006.

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– ALKS 8700, a novel prodrug of monomethyl fumarate, looks promising as an oral, disease-modifying treatment for relapsing forms of multiple sclerosis, according to interim findings from the phase 3 EVOLVE-MS-1 study.

The annualized relapse rate at a median follow-up of 0.93 patient-years (total, 497.1 patient-years) in 578 patients enrolled to date in the 2-year, open-label study was just 0.16, Robert T. Naismith, MD, reported during an emerging science session at the annual meeting of the American Academy of Neurology.

Further, a statistically significant 80% reduction from baseline was seen in the number of gadolinium-enhancing lesions in 374 patients who completed a 1-year MRI assessment (from a mean of 1.5 to 0.3), said Dr. Naismith of Washington University, St. Louis.

Patients enrolled in the ongoing study are adults aged 18-65 years (mean, 41 years) with confirmed relapsing-remitting MS (RRMS), Expanded Disability Status Scale score of 6.0 or less (mean, 2.7), and no evidence of relapse within 30 days prior to starting ALKS 8700. Those with progressive forms of MS are excluded, as are patients who are pregnant or breastfeeding, patients with a history of other clinically significant conditions, and those with clinically significant abnormal laboratory tests at screening or absolute lymphocyte counts less than 0.9 x 103/mcL.

Of those enrolled so far, 72.5% received prior MS therapies, and their mean time since onset and diagnosis of MS was 9.7 and 7.6 years, respectively. The mean number of relapses in the prior year was 0.8.

ALKS 8700, also known as BIIB098, is given at a dose of 462 mg twice daily for up to 96 weeks; planned enrollment in EVOLVE-MS-1 is approximately 900 patients, Dr. Naismith said.

The preliminary findings from EVOLE-MS-1, which is limited by its single-arm, open-label design, “lend credence to ALKS 8700 as an oral treatment for patients with relapsing-remitting MS,” he said.

 

 


In addition to continued evaluation for long-term safety and tolerability in the current study, ALKS 8700 is also being evaluated in combination with 240 mg of twice daily dimethyl fumarate (DMF; Tecfidera) in the 5-week, randomized, double-blind EVOLVE-MS-2 study, which is looking at the gastrointestinal tolerability of the combination in patients with RRMS.

Oral DMF is approved for RRMS, and has been shown to significantly reduce clinical and MRI disease activity, but is commonly associated with GI events. Monomethyl fumarate is the active metabolite of DMF, and as a prodrug of monomethyl fumarate, ALKS 8700 is being developed to work in a manner similar to that of DMF, but with improved GI tolerability, Dr. Naismith explained.

EVOLE-MS-1 is funded by Alkermes. Dr. Naismith has served as a consultant and/or speaker for Alkermes, as well as for Acorda, Bayer, Biogen, Genentech, Genzyme, EMD Serono, Novartis, and Teva. He has received research support from the National Institutes of Health and the National Multiple Sclerosis Society.

SOURCE: Naismith R et al. AAN 2018 Emerging Science Abstract 006.

 

– ALKS 8700, a novel prodrug of monomethyl fumarate, looks promising as an oral, disease-modifying treatment for relapsing forms of multiple sclerosis, according to interim findings from the phase 3 EVOLVE-MS-1 study.

The annualized relapse rate at a median follow-up of 0.93 patient-years (total, 497.1 patient-years) in 578 patients enrolled to date in the 2-year, open-label study was just 0.16, Robert T. Naismith, MD, reported during an emerging science session at the annual meeting of the American Academy of Neurology.

Further, a statistically significant 80% reduction from baseline was seen in the number of gadolinium-enhancing lesions in 374 patients who completed a 1-year MRI assessment (from a mean of 1.5 to 0.3), said Dr. Naismith of Washington University, St. Louis.

Patients enrolled in the ongoing study are adults aged 18-65 years (mean, 41 years) with confirmed relapsing-remitting MS (RRMS), Expanded Disability Status Scale score of 6.0 or less (mean, 2.7), and no evidence of relapse within 30 days prior to starting ALKS 8700. Those with progressive forms of MS are excluded, as are patients who are pregnant or breastfeeding, patients with a history of other clinically significant conditions, and those with clinically significant abnormal laboratory tests at screening or absolute lymphocyte counts less than 0.9 x 103/mcL.

Of those enrolled so far, 72.5% received prior MS therapies, and their mean time since onset and diagnosis of MS was 9.7 and 7.6 years, respectively. The mean number of relapses in the prior year was 0.8.

ALKS 8700, also known as BIIB098, is given at a dose of 462 mg twice daily for up to 96 weeks; planned enrollment in EVOLVE-MS-1 is approximately 900 patients, Dr. Naismith said.

The preliminary findings from EVOLE-MS-1, which is limited by its single-arm, open-label design, “lend credence to ALKS 8700 as an oral treatment for patients with relapsing-remitting MS,” he said.

 

 


In addition to continued evaluation for long-term safety and tolerability in the current study, ALKS 8700 is also being evaluated in combination with 240 mg of twice daily dimethyl fumarate (DMF; Tecfidera) in the 5-week, randomized, double-blind EVOLVE-MS-2 study, which is looking at the gastrointestinal tolerability of the combination in patients with RRMS.

Oral DMF is approved for RRMS, and has been shown to significantly reduce clinical and MRI disease activity, but is commonly associated with GI events. Monomethyl fumarate is the active metabolite of DMF, and as a prodrug of monomethyl fumarate, ALKS 8700 is being developed to work in a manner similar to that of DMF, but with improved GI tolerability, Dr. Naismith explained.

EVOLE-MS-1 is funded by Alkermes. Dr. Naismith has served as a consultant and/or speaker for Alkermes, as well as for Acorda, Bayer, Biogen, Genentech, Genzyme, EMD Serono, Novartis, and Teva. He has received research support from the National Institutes of Health and the National Multiple Sclerosis Society.

SOURCE: Naismith R et al. AAN 2018 Emerging Science Abstract 006.

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Key clinical point: ALKS 8700 looks promising for reducing the relapse rate in relapsing-remitting MS.

Major finding: The annualized relapse rate at 1 year was just 0.16 vs. 0.8 in the prior year.

Study details: One-year results from 578 patients in an ongoing phase 3, open-label study.

Disclosures: EVOLE-MS-1 is funded by Alkermes. Dr. Naismith has served as a consultant and/or speaker for Alkermes, as well as for Acorda, Bayer, Biogen, Genentech, Genzyme, EMD Serono, Novartis, and Teva. He has received research support from the National Institutes of Health and the National Multiple Sclerosis Society.

Source: Naismith R et al. AAN 2018 Emerging Science Abstract 006.

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