EUSA, through a vehicle called Huxley Pharmaceuticals, sold the rights to 3,4-DAPP to BioMarin in 2009, the same year that 3,4-DAPP was approved in Europe under the new name Firdapse.The licensing of Firdapse in 2010 in Europe led to a sharp increase in price for the drug. In some cases, this has led to hospitals using an unlicensed form rather than the licensed agent, as the price difference proved prohibitive. BioMarin has been criticized for licensing the drug on the basis of previously conducted research, and yet charging exorbitantly for it. A group of UK neurologists and pediatricians petitioned to prime minister David Cameron in an open letter to review the situation. The company responded that it submitted the licensing request at the suggestion of the French government, and points out that the increased cost of a licensed drug also means that it is monitored by regulatory authorities (e.g. for uncommon side effects), a process that was previously not present in Europe. A 2011 Cochrane review compared the cost of the 3,4-DAP and 3,4-DAPP in the UK and found an average price for 3,4-DAP base of £1/tablet and an average price for 3,4-DAP phosphate of £20/tablet; and the authors estimated a yearly cost per person of £730 for the base versus £29,448 for the phosphate formulation.Meanwhile, in Europe, a task force of neurologists had recommended 3,4-DAP as the firstline treatment for LEMS symptoms in 2006, even though there was no approved form for marketing; it was being supplied ad hoc.
The only other treatment approved for LEMS (Firdapse) is only approved for use in adults. Medical uses
Amifampridine is used to treat many of the congenital myasthenic syndromes, particularly those with defects in choline acetyltransferase, downstream kinase 7, and those where any kind of defect causes "fast channel" behaviour of the acetylcholine receptor. It is also used to treat symptoms of Lambert–Eaton myasthenic syndrome. Contraindications
Because it affects voltage-gated ion channels in the heart, it is contraindicated in people with long QT syndrome and in people taking a drug that might prolong QT time like sultopride, disopyramide, cisapride, domperidone, rifampicin or ketoconazol. It is also contraindicated in people with epilepsy or badly controlled asthma. Adverse effects
The dose-limiting side effects include tingling or numbness, difficulty sleeping, fatigue, and loss of muscle strength.Amifampridine can cause seizures, especially but not exclusively when given at high doses and/or in particularly vulnerable individuals who have a history of seizures. Interactions
The combination of amifampridine with pharmaceuticals that prolong QT time increases the risk of ventricular tachycardia, especially torsade de pointes; and combination with drugs that lower the seizure threshold increases the risk of seizures. Interactions via the livers cytochrome P450 enzyme system are considered unlikely. Pharmacology
Mechanism of action
In Lambert–Eaton myasthenic syndrome, acetylcholine release is inhibited as antibodies involved in the host response against certain cancers cross-react with Ca2+ channels on the prejunctional membrane. Amifampridine works by blocking potassium channel efflux in nerve terminals so that action potential duration is increased.