Therapeutics Q&A:

Dalfampridine (Ampyra, Acorda Therapeutics) is a potassium channel blocker indicated to improve walking ability in patients with multiple sclerosis (MS) compared to placebo, as demonstrated by an increase in walking speeds. The approval of Ampyra has been highly anticipated: It is the first therapy for MS approved by the FDA since 2004 and is the first therapy green lighted specifically to treat an MS symptom.

It's important to note that Ampyra is contraindicated in patients with a history of seizures, and the risk of seizure increases when Ampyra is administered above the recommended dose of one 10mg tablet twice daily, approximately 12 hours apart. The drug's manufacturer notes that no additional benefit was demonstrated at doses greater than 10mg twice daily. Ampyra is contraindicated in patients with moderate to severe renal impairment.

Where will dalfampridine fit in the treatment regimen for someone newly diagnosed with MS? When would you begin treatment with dalfampridine? What is its role for patients already being treated for MS?
Dalfampridine is not an immune-modulating agent, so it is not going to replace or be an alternative to those well-known disease-modifying agents, says Norman Kachuck, MD, Associate Professor of Neurology at the Keck School of Medicine of USC and Director of the MS Comprehensive Care and Research Center.

“I really have no compunctions about using this as medicine general nostrum for all things bad, symptomatically in MS,” he says. “It may work for all sorts of different complaints that have nothing to do with walking. I've been using this medicine in its compounded version for a number of decades.” Dr. Kachuck says patients receive numerous potential benefits from dalfampridine that are not easily predicted.

Patients taking a compounded form of fampridine may not want to switch over if their symptoms are well-controlled, he says, but adds that the newly approved formulation of dalfampridine offers benefits. “A lot of people who are starting will have a reasonable co-pay, it's FDA approved, it's a pharmacokinetically stable agent, and that will make community neurologists comfortable,” Dr. Kachuck adds. Some observers have noted that compounded formulations of fampridine can lack consistency.

How long of a trial is necessary to determine if dalfampridine will be effective for a given patient?
“It usually takes a month to see benefits, but it depends on the sensitivity of the doctor and patient,” Dr. Kachuck contends.

Much depends on patient counseling. “If the patient is not vigilant or the doctor isn't patient, then you won't know. If neurologists are good about saying, ‘We're giving it to you so you can get through Costco without a rest' and detailing how the regimen will help, then patients will stand a higher chance of seeing some level of success,” he adds.

“Also, you have to tell the patient that it might have any sort of effect, so they need to keep a diary of all their various symptoms/complaints and any changes over the course of therapy. What we don't have now is the chance to titrate. So it will either work or won't,” he says.

Are there other potential applications of dalfampridine, beyond walking improvement?
As noted by Dr. Kachuck, dalfampridine could affect motor symptoms other than walking ability. “I've got patients presently taking dalfampridine who have just one limb left and they say they've got the capacity to use the joystick on their wheelchair more effectively,” Dr. Kachuck says. “I have patients who don't even have a functioning limb but who say their neck control, or their breath control, or their ability to speak are improved.”

The mechanism of action isn't known, but are there any theories on how the drug works?
The mechanism of action has not been fully elucidated, but from a pharmacological viewpoint, the calcium channel blocking properties of dalfampridine and its effects on action potential conduction in demyelinated nerve fiber preparations have been extensively characterized.¹ “At low concentrations that are relevant to clinical experience, in the range of 0.2–2µM (18 – 180ng/ml), 4-AP is able to block certain voltage-dependent K+ channels in neurons,” writes Dr. Kachuck.¹ He says that it is this characteristic that seems to explain the ability of the drug to restore conduction of action potentials in some critically demyelinated nerve fibers.

How will dalfampridine be priced?
According to figures released by Acorda Therapeutics, Ampyra will cost about $13,000 a year wholesale or $1,056 for each 30-day supply. Physicians and patients can contact Ampyra Patient Support Services at 888-881-1918 for more information about patient assistance and co-pay mitigation programs. “An enormous number of people will want to try it, but the insurers will try and push back because of the cost,” Dr. Kachuck predicts. He estimates about one-third of the MS population will eventually take the drug.

Norman J. Kachuck, MD is an Associate Professor of Clinical Neurology at the USC Keck School of Medicine, Clinical Chief of the Multiple Sclerosis and Neuroimmunology Division of the Department of Neurology, and Co-director of the USC MS Comprehensive Care Center.

1. Kachuck, N. “Sustained oral release fampridine in the treatment of multiple sclerosis.” Expert Opin. Pharmacother. 2009; 10(12).