AT ECTRIMS 2016
LONDON (FRONTLINE MEDICAL NEWS) – Patients with relapsing-remitting multiple sclerosis reported that their ability to walk was significantly improved following 6 months of treatment with extended-release dalfampridine – compared with patients on placebo – in a double-blind, randomized trial.
In the ENHANCE study, 43.2% of the 315 patients treated with extended-release dalfampridine (dalfampridine-ER; Ampyra) and 33.6% of the 318 who were given placebo achieved a clinically meaningful improvement of 8 or more points on the 12-item MS Walking Scale (MSWS-12) measured at week 24.
The odds ratio (OR) was 1.61, highlighting a significant difference between the two study arms (P = .006).
“This is one of the only studies to use a PRO [patient-reported outcome] as the primary outcome and to use an a priori threshold of clinical meaningfulness,” said Jeremy Hobart, MD, of Plymouth Hospitals NHS Trust (England), who reported the study’s findings at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis. This is an important, and challenging, development in MS trials, he added.
“We are all aware that walking impairments are one of the hallmarks of multiple sclerosis,” Dr. Hobart said, adding that it affects the “vast majority” of patients.
Dalfampridine-ER, which is known as prolonged-release fampridine in Europe, is the only therapy licensed to improve walking in MS, he observed. The pivotal studies that led to the drug’s approval, however, were of relatively short duration and the ENHANCE study was conducted to answer questions that have been raised about the durability of its effect on patients’ mobility.
Patients in ENHANCE received either dalfampridine-ER at a twice-daily dose of 10 mg or placebo for 24 weeks. The mean age of patients in each group was 49 and 48 years, respectively, and 59% and 57% of recruited patients in each arm were female. Patients were stratified according to their baseline Expanded Disability Status Scale (EDSS) score, with 78% and 77% in the dalfampridine-ER and placebo groups having a score of 6 or less.
Dr. Hobart noted that the mean change in MSWS-12 scores over time and an analysis of the cumulative proportion of responders at any particular threshold score on the MWSW-12 showed a clear benefit of dalfampridine-ER treatment over placebo.
The study investigators also assessed patients’ balance via the Timed Up and Go (TUG) test, with a benefit threshold set at obtaining at least a 15% or more improvement at 24 weeks. Significantly more dalfampridine-ER–treated than placebo-treated patients achieved this threshold (43.4% vs. 34.7%; OR, 1.46; P = .03).
There was a significant improvement between the two study arms on the 29-item physical scale of the Multiple Sclerosis Impact Scale (P less than .001).
However, there was no change seen in upper extremity function, with similar mean changes in the Berg Balance Scale score and the ABILHAND score at 24 weeks. The mean baseline scores for both of these measures were high, Dr. Hobart observed, which probably affected the findings. That said, patients with a baseline EDSS of 6 or higher had greater improvement in ABILHAND scores if they had received dalfampridine-ER, compared with placebo, but the difference was not statistically significant.
The safety profile was consistent with what has been seen in other trials, Dr. Hobart said, and there were no new safety concerns raised.
“The findings from ENHANCE expand and tend to … confirm the favorable risk-benefit profile established in prior pivotal trials,” he said.
Biogen sponsored the study. Dr. Hobart disclosed receiving fees, honoraria, and research support from Biogen, Acorda, Genzyme, Global Blood Therapeutics, Merck Serono, Novartis, Tigercat, and Vanita.