Ampyra Approved to Improve Walking for Individuals with MS
The United States Food and Drug Administration (FDA) has approved Ampyra™ (dalfampridine), an oral, timed-release medication developed to improve the conduction of impulses between damaged nerves of the central nervous system (CNS).
Phase III clinical trials showed that a greater number of individuals with MS experienced improvement in walking speed when taking Ampyra, compared to when taking a placebo. An FDA application was submitted in January 2009, and following an extension of the FDA’s review process in October 2009, Ampyra was granted approval on January 22, 2010. Ampyra is the first drug to be approved to improve walking speed in individuals with MS.
Ampyra (pronounced "am-PEER-ah") was developed by Acorda Therapeutics and is manufactured by Elan Corporation. Formerly known as Fampridine-SR, Ampyra is a sustained-release version of 4-aminopyridine (4AP). In earlier studies, larger doses of the drug were given and the risk of seizures became a concern. Given in extended-release tablets, the risk of seizures did not differ from the placebo group.
"We are all very pleased with the approval of this new treatment for symptom management in MS," states MSAA Chief Medical Officer Jack Burks, MD. "Acorda Therapeutics reports that up to 85 percent of individuals with MS have some type of difficulty with walking, most of whom find this symptom to be among the most challenging issues resulting from their MS. The majority of my patients experience problems with mobility, so this approval comes as welcomed news to the entire MS community, especially since it has shown positive results with both relapsing and progressive forms of MS.
"Anyone interested in this drug for symptom management should consult his or her physician, who can help to determine if this drug is appropriate. Those with a history of seizures or with moderate to severe kidney problems are advised against using Ampyra.
"Following the instructions for correct dosing is absolutely essential. Taking more than one tablet within 12 hours, or crushing or splitting a tablet, will increase the risk for seizures. Some patients tend to think that taking more of a symptom-management drug will result in greater effectiveness, but this is definitely not the case with this type of medication. I strongly advise patients not to exceed the recommended dosing, as stated later in this article.
"The original version of this drug, 4-aminopyridine, has been under development for quite a long time. I have more than 20 years of experience observing patients who have taken the drug. They were able to obtain 4-aminopyridine through a prescription from their primary doctor, and then had it filled at a compounding pharmacy. My concern for those patients centered on the risk of increased seizures with a compounded drug. This new, timed-release formulation reduces the risk of seizures significantly.
"Overall, I am looking forward to seeing how patients will feel once they are prescribed Ampyra. I would expect to see an improvement in the quality of life for many patients."
When asked about the potential of Ampyra and if it may be able to help with other symptoms, Dr. Burks explains,"Initially, as we learn more about the effects of Ampyra, I recommend that it is only used for the FDA indication to improve walking. However, there was encouraging data in symptoms such as strength and endurance in the clinical trials, but the drug was not given specific approval for these symptoms. In the future, I expect more clinical trials will continue to evaluate the effects of Ampyra in patients with other symptoms, such as weakness, reduced endurance, fatigue, cognition, vision, and many other MS symptoms."
How Ampyra Works
Nerves (also known as axons) work similarly to electrical cords and are designed to carry impulses, or "messages," to and from the brain, spinal cord, and other parts of the body. Just as electrical cords are insulated with a protective covering, the body’s nerves have a protective fatty covering known as myelin. With MS, areas of myelin along the nerves of the CNS become damaged, and the conduction of nerve impulses is affected.
Potassium ions are necessary for the nerve to have an electric current, which enables nerve impulses to flow along the nerve fibers. These ions work through tiny holes or channels on the surface of the nerves. When myelin is damaged, these channels become exposed, potassium ions leak from these channels, and the electrical current is interrupted.
Ampyra works by blocking the exposed potassium channels and improving the conduction of nerve impulses. This increase in communication between damaged neurons may promote greater neurologic function, as indicated by an improvement in walking speed in those who responded to the drug in clinical trials. >
Clinical Trial Results
Studies included individuals with any one of the four major types of MS: relapsing remitting, secondary progressive, progressive relapsing, and primary progressive. A total of 540 patients participated in the two Phase III studies, which were randomized, placebo-controlled, parallel grouped, and double-blinded. During the active-treatment periods of the Phase III studies, participants were given 10 mg twice daily of Ampyra.
Patients were excluded from the trials if they had a history of or evidence of previous seizure activity, or if they had an MS exacerbation within 60 days of the trial. In the latter Phase III study, patients with "severe renal impairment" (poor kidney function) were also excluded.
Results from both Phase II and Phase III studies showed that a significantly greater number of "Timed Walk Responders" were in the treated group versus the placebo group. A "Timed Walk Responder" refers to someone who experienced a consistent improvement in walking speed during the "Timed 25-Foot Walk" (T25FW) when taking the drug, versus his or her timed walking speed when taking a placebo (inactive drug). The T25FW is a standardized test, where a patient is timed with a stopwatch while walking a distance of 25 feet along a set walkway.
A 21-week, Phase III, multi-center trial in people with MS found that approximately 35 percent of the treated group showed consistent improvement in walking speed, versus just over 8 percent of the placebo group. In a second 14-week, Phase III trial, approximately 43 percent of the treated group showed consistent improvement in walking speed, versus just over 9 percent of the placebo group.
Ampyra is a symptom-management drug to improve walking in MS patients. It may be given in conjunction with any FDA-approved disease-modifying therapy. These include the interferons (Avonex®, Betaseron®, Extavia®, and Rebif®), glatiramer acetate (Copaxone®), mitoxantrone (Novantrone ®), and natalizumab (Tysabri®). It may be given with other symptom-management drugs, but patients should check with their doctor before combining Ampyra with other medications.
Ampyra is an oral, timed-release tablet approved to treat walking problems in MS. One 10-mg tablet is taken twice daily (every 12 hours). Taking greater amounts of this drug will increase the risk for seizures. If a dose is missed, patients must skip the missed dose and wait until the next dose is due, as patients may not take two doses less than 12 hours apart. The timed-release tablets must be taken whole and not split, crushed, chewed, broken, or dissolved prior to swallowing, as this will release too much of the drug into the body at one time, increasing the risk for seizures.
Individuals with a history or evidence of seizures, or with moderate to severe kidney problems, should not be given Ampyra. Kidney function is important, since nearly all of this medication is removed from the body through the kidneys. If the kidneys are not functioning properly, levels of the drug will rise and increase the risk for seizures.
Individuals should tell their doctor if they have any other medical conditions, and also provide a list of medications and supplements they are presently taking. Patients may not be given Ampyra if they are taking any other medication containing 4-aminopyridine.
Ampyra has not been tested in women who are pregnant or nursing, or in children and young adults under the age of 18, so the safety of this drug in these populations is not known. Based on animal studies, this drug could cause fetal harm, so women who are pregnant should not take Ampyra. Nursing mothers should either discontinue the drug or discontinue nursing. In geriatric populations, kidney function should be evaluated carefully before prescribing Ampyra and while taking Ampyra, since elderly patients are more likely to have decreased renal (kidney) function.
According to the FDA, the most common side effects reported for Ampyra include urinary tract infection, insomnia, dizziness, headache, nausea, weakness, back pain, balance disorder, swelling in the nose or throat, constipation, diarrhea, indigestion, throat pain, and burning, tingling, or itching of skin.
Ampyra is expected to be available in the United States by prescription in March 2010. It will be distributed exclusively through a network of specialty pharmacies, which will be coordinated by Ampyra Patient Support Services.
Beginning January 28, 2010, consumers as well as healthcare professionals may contact the Ampyra Patient Support Services at (888) 881-1918 for drug information and for help in processing prescriptions, facilitating insurance coverage, and accessing benefits available through reimbursement assistance and patient assistance programs. Consumers and healthcare professionals may also visit www.ampyra.com at any time for more information. To speak with one of MSAA’s Helpline consultants, please call (800) 532-7667.
Written by Susan Wells Courtney, MSAA Senior Writer & Creative Director
Reviewed by Dr. Jack Burks, MSAA Chief Medical Officer