Ampyra (dalfampridine) shows long-term efficacy in improving walking ability in people with multiple sclerosis, according to a study evaluating the treatment’s use in progressive and relapsing MS patients over two years.
The study, “Monitoring long-term efficacy of fampridine in gait-impaired patients with multiple sclerosis,” was published in the journal Neurology.
Ampyra (known as Fampyra [fampridine] in Europe) is currently the only drug approved by the U.S. Food and Drug Administration (FDA) to improve walking in adults with MS, a function severely impaired in about 75 percent of these patients. Prolonged-release Ampyra capsules improve signal conduction in nerve fibers damaged by MS, a result of immune system attacks against myelin.
While short-term treatment with prolonged-release Ampyra has shown beneficial effects on patents’ walking speed and endurance, the therapy’s long-term safety and efficacy was also investigated.
Researchers at the University of Zurich performed a randomized, double-blind, placebo-controlled clinical trial to assess the two-year effects of prolonged-release Ampyra on walking ability. It was an extension of the FAMPKIN trial (NCT01576354), in which enrolled patients were treated for six weeks with either oral placebo or prolonged-release Ampyra.
Of 55 patients who completed FAMPKIN, 53 enrolled in the two-year Ampyra extension trial. Investigators used several functional tests, including the Timed 25-Foot Walk (T25FW), 6-Minute Walk Test (6MWT), and 12-item MS Walking Scale (MSWS-12) to determine patient outcomes.
Results confirmed the good tolerability of prolonged-release Ampyra in as a long-term MS treatment, and a positive impact on walking speed and endurance.
“[W]e found a significant correlation between functional improvements in the clinical gait tests … and the self-perceived walking ability,” Dr. Linard Filli, the published study’s lead author and a researcher with the FAMPKIN trial, said in an interview with Multiple Sclerosis News Today.
MS manifests in different forms, and the trial included patients with relapsing-remitting, primary progressive, and secondary progressive MS. In the interview, Multiple Sclerosis News Today asked Dr. Filli if his team saw differences in patient outcomes and response to Ampyra according to MS type, and whether particular subgroups seemed to benefit most.
“We did not find a valid correlation between patient’s responsiveness and their specific type of MS in our study. We found both well responding patients and non-responders in each of the different MS subtypes,” Filli said. “Importantly, the results of our study and previous trials demonstrate that Ampyra also exerts significant positive effects in patients with chronic progressive MS, where alternative treatment options to improve walking function are virtually absent.
“We are currently screening for demographic and clinical factors that might be used as predictors of patients’ (short- and long-term) responsiveness to Ampyra,” he said.
Analyses of functional tests results showed that a proportion of patients changed their response to prolonged-release Ampyra over the two years of treatment: a significant 10% improvement in T25FW and 6MWT was achieved by half of all patients, versus one-fifth (T25FW) and barely one-third (6MWT) in the original FAMPKIN study.
Long-term treatment proved particularly beneficial to patients failing to reach the initial 10% improvement threshold in the T25FW and 6MWT. In fact, 40% of them exhibited improvements greater than 10% after two years of prolonged-release Ampyra treatment.
This highlights that patients may respond very differently to the therapy, and that those with a moderate to poor short-term response can improve walking ability over time with the treatment.
But some patients who responded very well to the Ampyra initially may develop resistance to the drug over the longer term.
“We observed both patients with increasing and decreasing responsiveness to Ampyra over time. In average, however, the results of our study demonstrated that the responsiveness in the total study population generally increased over time. The fact that patients change their responsiveness to Ampyra in either direction emphasizes the importance of regular re-evaluation of drug efficacy over time,” Filli said.
These results support the need to re-evaluate regularly individual patient response to prolonged-release Ampyra in real clinical settings, so that treatment can be optimized accordingly.
“[P]eriodic drug holidays seem to be crucial to adapt/optimize the therapy with Ampyra, i.e. stopping treatment in patients losing their responsiveness over time,” Filli said. “On the other hand, regular assessments of the efficacy of Ampyra in a given patient might also help to uncover drug efficacy in initially non-responding patients.”
The extended study was performed over two years. But Filli said patients are still being followed and data collected: “The FAMPKIN extension trial was extended for 3 more years and thus will run over a period of 5 years in total. The majority of participants are currently in their last year of the study.”
Dr. Andrew Blight, chief scientific officer at Acorda Therapeutics, the biopharmaceutical company that developed Ampyra, described the feedback from healthcare providers and patients treated with the drug.
“Ampyra has been tried by more than 120,000 people with MS in the United States, and tens of thousands more around the world. It has a meaningful impact for many people who try it; walking is a basic function that affects many other aspects of our lives,” Blight said.
“Like most medicines, not everyone will benefit,” he added. “Because MS is both a variable and progressive disease, people who do not respond at one point to Ampyra may see improvements later on. The data from this study is important to help medical professionals in determining how to prescribe Ampyra and assess its value to a particular individual.”
Acorda recently reported that it lost rights to four of five patents it holds on Amypyra in a recent U.S. District Court decision. It plans to appeal, but the ruling opens the possibility of generic versions of Ampyra becoming available, perhaps in 2018.
Blight said the company is developing other potential treatments for MS. “We are currently studying a drug called rHIgM22, which may help to stimulate remyelination in damaged nerves. This would be a complementary therapy to disease-modifying drugs that try to halt the progression of disease. M22 is currently in Phase 1 testing, and we expect to complete our ongoing clinical trial by the end of the year.”
A full transcript of the interviews with Dr. Linard Filli and Dr. Andrew Blight can be found here.