“Walking Drug” Approved for All MS Patients
Friday the FDA announced its approval of dalfampridine* (Ampyra; Acorda/Elan) to improve walking in all patients with multiple sclerosis. The drug, in the form of a sustained-release 10-mg tablet, has been assessed in at least 4 well-controlled MS trials; but a non-sustained-release version of the drug, which is believed to enhance nerve conduction by blocking potassium (or possibly, calcium) channels, has been clinically studied in MS since at least 1990.**
The overriding theme of these earlier trials was that the compound has a narrow therapeutic window—meaning that it improves mobility, but drug toxicity (ie, seizures, acute confusion) is associated with fickle serum-concentration spikes. This observation was the rationale for developing a sustained-release formulation, which is intended to produce adequate drug concentrations while averting the toxicity-inducing peak levels.
According to Ampyra’s prescribing information, approval is based on 2, 14-week, multicenter, randomized placebo-controlled trials conducted in North America: a double-blind phase 3 study (N = 301) and a sequential single-/double-blind study (N = 239). Efficacy is supported by significantly improved speeds of a timed 25-foot walk in about one quarter to one third of treated patients (the percentage differences between dalfampridine- and placebo-treated patients). Positive effects on ambulation were seen in all forms of MS.
Although the Ampyra label does not carry a so-called black-box warning, the FDA advises of the risk of seizures, particularly in patients taking higher-than-recommended doses and in individuals with renal dysfunction. (Last time I checked, the baseline risk of seizure in MS patients was about 5%.) The maximum recommended dosage of the drug is 10 mg (1 tablet) every 12 hours. The label also states that a routine injection of interferon beta-1b (ie, Betaseron or Extavia) does not interfere with the pharmacokinetics of Ampyra.
Share prices of Acorda spiked at end-of-day trading on Friday, after momentarily plunging in mid-October when the FDA questioned the drug’s safety and the meaningfulness of the trials’ outcomes.
* Aka pyridine-4-amine, 4-aminopyridine, 4-pyridinamine, 4-pyridylamine, and fampridine.
** A directed PubMed search reveals that the first well-controlled trial of 4-aminopyridine was published in 1990 (Polman CH et al. 4-Aminopyridine in multiple sclerosis. Ann Neurol. 1990;28:589).