Email this pageDrug Improves Mobility for Some MS Patients
Q & A with Andrew Goodman, M.D. about Fampridine-SR»
The experimental drug fampridine (4-aminopyridine) improves walking ability in some individuals with multiple sclerosis. That is the conclusion of a multi-center Phase 3 clinical trial, the results of which were published Feb. 28 in The Lancet.
“This study indicates that fampridine could represent an important new way to treat multiple sclerosis and perhaps become the first drug to improve certain symptoms of the disease,” said neurologist Andrew Goodman, M.D., chief of the Multiple Sclerosis Center at the University of Rochester Medical Center and lead author of the study. “The data suggest that, for a subset of MS patients, nervous system function is partially restored while taking the drug.”
Goodman, who has been a consultant and advisor to Acorda for its fampridine studies in MS, also discusses the findings in more depth in a Q&A.
The study evaluated a sustained-release formulation of the drug, Fampridine-SR, which is being developed by Acorda Therapeutics, Inc. The company, which funded the study, announced that it has submitted a new drug application to the U.S. Food and Drug Administration.
Scientists believe that fampridine improves the transmission of signals in the central nervous system of some MS patients by blocking potassium ion channels, which regulate normal electrical activity. In laboratory experiments involving nerve fibers with myelin that was damaged in a manner that mimics MS, scientists found that blocking these channels results in a recovery of signal conduction.
In the Phase 3 study led by Goodman, the effects of Fampridine-SR were tested in 301 adult MS patients at 33 locations in the United States and Canada over a 14-week period. Three quarters of the participants took the drug and the rest were given a placebo.
In the past, MS drugs have been evaluated based largely on their ability to prevent relapses. Because the goal of this study was to assess changes in function, the researchers instead sought to evaluate participants’ mobility and muscle strength, not the disease process itself. In prior studies, Goodman and his colleague, the late Steven Schwid, M.D., had validated new methods to measure changes in gait, or walking speed over distance. Employing these methods in The Lancet study, they found that 34.8% of those receiving the drug experienced an improvement – an average of about a 25 percent increase – in the speed required to walk 25 feet. That compared to only 8.3% of the participants in the placebo group who experienced such an improvement.
“During the course of the disease, many MS patients experience a decline in mobility, and this disability has a major impact in terms of quality of life,” said Goodman. “As a clinician, I can say that improvement in walking speed could have important psychological value; it may give individuals the potential to regain some of the independence that they may have lost in their daily lives.”
Other drugs that have been approved to treat MS either counter nervous system inflammation, or they suppress the immune system generally. While these drugs can be effective at preventing new relapses and slowing the progression of the disease, there are no treatments currently available that improve impaired function, such as mobility problems.
Participants in the trial were allowed to continue to take most other medications for MS, and researchers did not observe any negative interactions. However, 11 patients (4.8%) in the fampridine-treated group discontinued the study due to side effects. Only two of these were considered by the investigators to be possibly related to treatment.
Co-authors of the study include Schwid; Theodore Brown, M.D., M.P.H. with Evergreen Hospital Medical Center in Kirkland, Wash.; Lauren Krupp, M.D., with Stony Brook University; Randall Shapiro, M.D., with the Minneapolis Clinic of Neurology; and Ron Cohen, M.D., Lawrence Marinucci and Andrew Blight, Ph.D., all with Acorda Therapeutics.
Q&A with Dr. Andrew Goodman about Fampridine-SR
The results of the Phase 3 clinical trial published in The Lancet showed that the experimental drug fampridine improves gait for approximately 35% of the MS patients who took the drug by an average of 25 percent. The doctor who led the study, neurologist Andrew Goodman, M.D., discusses the results more fully.
There are already a number of approved treatments available for MS. How does fampridine differ?
The existing approved treatments for MS are called disease-modifying agents. These are various therapies that address the fundamental disease process that causes damage to the central nervous system, specifically, damage to myelin – the fatty tissue that insulates nerve fibers – and damage to the nerve fibers themselves. These treatments all modulate, modify, or prevent the inflammation that is at the heart of the disease or suppress the immune system in a broad way in the hope that it will have an impact on the inflammation in the central nervous system.
Fampridine represents a new approach to therapy that impacts function, as opposed to the disease process. The specific types of functions we looked at in this and several other studies we have conducted with this drug are walking and leg strength. These are common problems people encounter with MS and are a major part of the overall impact and disability that MS causes.
This study represents hopefully a different, yet complementary, approach to the existing disease-modifying treatments. The idea of disease-modifying treatment is to prevent the damage in the central nervous system from happening. However, when the damage has already been done, fampridine represents for some patients an opportunity to potentially improve function while taking the drug.
What does the ability to improve walking speed mean for MS patients?
In this particular study, what we observed was that among the people who met the criteria for consistently improved walking speed, they themselves were able to identify that they were better. And they were better in a whole realm of aspects of MS affecting their walking and ability to function on their feet. A 12-question scale was used to evaluate things such as how far they could walk, how fast they could walk, and how long they could stay on their feet, and all of these indicators improved. Not only did the timed-walk responders indicate that they were doing better, this was also apparent to the study clinicians even though they were blinded to whom was receiving the drug.
The standard yardstick for evaluating MS treatments has been to use methods that measure the progression of the disease, including changes in MRI scans of the brain, clinical relapses, and the progression of disability over time. These have been used in measuring disease-modifying treatments; however, this drug is different because it is intended to improve function.
In previous studies we found that the most consistent and sensitive measurement of changes in walking ability was the repeated timing of the 25-foot walk and that any change of more than 20 percent (either better or worse) was significant. We also found that there was almost a one-to-one correlation between how fast someone could walk and how far they could walk. Furthermore, we found that there was a very strong correlation between the speed they could walk and the overall measurement of disability in a tool that is most commonly used in MS clinic trials called the Estimated Disability Status Score (EDSS) that looks at many aspects of disability.
The study shows that the drug improves walking ability for some but not all patients. How will clinicians determine which patients are appropriate for treatment?
The results so far have not given us a clear way to predict who will respond to treatment. The data show that for people who have clearly slowed walking as a result of MS, roughly a third will improve to the point where we consider them responsive to the drug.
Absent a way to predict who will respond to treatment, physicians will need to approach this in a practical manner. They would need to select people who have walking difficulties, prescribe the medication, and monitor how they do. This is a typical part of the practice of medicine. If a patient meets the criteria for a treatment, then you try it and then make your best judgment as to how they are tolerating it and how effective it is and determine whether it is worth continuing.
Were there any notable side effects or negative interactions with other MS drugs that patients may be taking?
We observed some common side effects such as dizziness, insomnia, and fatigue. In terms of negative interactions with other MS treatments, we actually specifically allowed and encouraged the use of other disease-modifying and symptom treatments (e.g. bladder control medications) to see whether or not there would be negative interactions. We did not identify any in this study.
