Prolonged-Release Fampridine Induces Sustained Clinically Meaningful Improvements in Walking Ability in People with Multiple Sclerosis: Results from the ENHANCE Trial (P6.364)

Objective: ENHANCE was a phase 3, multicenter, randomized, double-blind, placebo-controlled trial to evaluate whether prolonged-release (PR) fampridine 10 mg twice daily (dalfampridine extended release in US) provides sustained clinically meaningful benefits versus placebo on patient-reported functional outcome measures in people with MS (PwMS). Background: Walking impairment affects 80% of PwMS; therefore, maintaining and improving mobility are high priorities for these patients. While clinical trials, observational studies, and patient reports demonstrate consistent mobility benefits with PR-fampridine, patient impact, including clinical meaningfulness and durability of benefits, deserves further exploration. Design/Methods: ENHANCE enrolled PwMS age 18–70 years, with progressive or relapsing MS, and impaired walking (EDSS 4–7). The primary endpoint was percentage of people with mean 12-item MS Walking Scale (MSWS-12) score improvements ≥8-points from Baseline over 24 weeks. Secondary endpoints included: Timed Up and Go (TUG) speed, MS Impact Scale physical subscale (MSIS-29 PHYS), static balance (Berg Balance Scale [BBS]), and upper extremity function (ABILHAND questionnaire). Safety was also assessed. Results: Overall, 636 PwMS were randomized to PR-fampridine 10 mg (n=317) or placebo (n=319) twice daily; 633 (n=315 PR-fampridine; n=318 placebo) had ≥1 dose of PR- fampridine or placebo and ≥1 post-Baseline efficacy assessment. Significant treatment differences were observed for PR-fampridine versus placebo on clinically meaningful improvement in the MSWS-12 (43.2% versus 33.6% PwMS; OR: 1.61 [95% CI: 1.15, 2.26]; P =0.006), in a ≥15% mean improvement on TUG speed (43.4% versus 34.7% PwMS; OR: 1.46 [95% CI: 1.04, 2.07]; P =0.030), and in greater mean improvements in the MSIS-29 PHYS (least square mean difference: −3.31 [95% CI: −5.13, −1.50]; P Conclusions: Sustained clinically meaningful benefits with PR-fampridine were observed on self-reported walking ability, transfer and walking speed, and self-reported physical impact of MS. Safety was consistent with the known PR-fampridine profile. Study Supported by: Biogen Disclosure: Dr. Hobart has received personal compensation for activities with Biogen and Genzyme for consulting. Dr. Hobart has received research support from Acorda, Biogen, Genzyme, Global Blood Therapeutics, Merck Serono, Novartis, Tigercat, Vanita. Dr. Ziemssen has received personal compensation for activities with Dr. Feys has received personal compensation for activities with Biogen, Novartis, and Excemed as an advisory board member or speaker. Dr. FEys has received personal compensation in an editorial capacity for Multiple Sclerosis Journal. Dr. Linnebank has received personal compensation from Bayer HealthCare, Biogen, Genzyme, Merck, Novartis and Teva. Dr. Goodman received personal compensation for activities with Abbvie, Acorda Therapeutics, Atara, Bayer HealthCare, Biogen, Novartis, Sanofi-Genzyme, and Teva. Dr. Goodman has received research support from Acorda, Avanir, Biogen, EMD-Serono, Novartis, Ono, Roche, Sanofi-Genzyme, Sun and Teva. Dr. Farrell has received personal compensation for activities with Biogen Idec, Canbex, GW and Teva as a consultant and as an advisor. Dr. Englishby has received personal compensation for activities with Biogen Idec. Dr. Englishby holds stock and/or stock option in Biogen Idec. Dr. McNeill has received personal compensation for activities with Biogen as an employee. Dr. Chang has received personal compensation for activities with Biogen as an employee. Dr. Chang holds stock and/or stock options in Biogen. Dr. Metha has received personal compensation from Biogen and Amgen as an employee. Dr. Mehta holds stock and/or stock options with Biogen. Dr. Elkins has received personal compensation for activities with Biogen as an employee. Dr. Elkins holds stock and/or stock options with Biogen.