WASHINGTON -- The Jacobus Pharmaceutical's oral formulation of amifampridine (Ruzurgi) late Monday for Lambert-Eaton myasthenic syndrome (LEMS), surprising many who expected that (Firdapse) had closed the door on competition.
Ruzurgi is approved for pediatric patients age 6 to less than 17, whereas Firdapse's indication is for adults ages 17 and older. Both products were designated as orphan drugs.
The Jacobus product, which the small, privately held company had distributed free for many years under compassionate-use rules, is the first drug approved specifically for pediatric patients with LEMS.
"This approval will provide a much-needed treatment option for pediatric patients with LEMS who have significant weakness and fatigue that can often cause great difficulties with daily activities," said Billy Dunn, MD, director of the Division of Neurology Products in the FDA's Center for Drug Evaluation and Research, in announcing the decision.
How and why the FDA approved two versions of the same drug for LEMS made by different manufacturers is still not fully clear, although neither company held exclusive rights to the drug, which is off patent. The FDA is known to be liberal with orphan drug designations -- for example, the agency has now approved six medications for hereditary angioedema, all as orphan drugs, with small differences in indications as the rationale.
On Tuesday morning, after Ruzurgi's approval was announced, , signalling that investors had believed Firdapse's orphan-drug status would keep the Jacobus product off the market. But Firdapse's limitation to adult patients evidently left the door open for Jacobus to gain the pediatric indication -- even though, as Jacobus provided data only from adults.
Some analysts speculated that prompted the FDA to make sure that it had competition. Before and after former FDA Commissioner Scott Gottlieb left office a month ago, he was highly critical of drug monopolies and their role in propping up drug prices.
LEMS background
LEMS is characterized by muscle weakness and is caused by an autoimmune reaction in which antibodies are formed against voltage-gated potassium channels, causing the amount of acetylcholine released by the nerves to be reduced. Symptoms can be life threatening when the weakness involves the respiratory muscles.
The condition is also associated closely with cancer, particularly small cell lung cancer, with LEMS onset preceding or coinciding with a cancer diagnosis. Overall, LEMS prevalence is about 3 per 1,000,000 people worldwide, although its pediatric prevalence specifically in children is not known.
Amifampridine blocks presynaptic potassium channels and subsequently increases presynaptic calcium concentrations and enhances acetylcholine release. Other than amifampridine, treatments may include immunosuppressants and pyridostigmine, although their efficacy is modest at best.
The FDA approval for pediatric use was supported by evidence from studies of the drug in adults with LEMS, pharmacokinetic data in adult patients, pharmacokinetic modeling and simulation to identify the dosing regimen in pediatric patients, and safety data from pediatric patients age 6 to less than 17 years.
Its effectiveness was established by a randomized, double-blind, placebo-controlled in which patients were taking amifampridine for at least three months prior to entering the study. The study compared patients continuing the drug to patients switched to placebo, with effectiveness measured by how long it took a patient to rise from a chair, walk three meters, and return to the chair for three consecutive laps without pause. Patients who continued on amifampridine experienced less impairment than those on placebo. Patients who switched to placebo also perceived greater weakening in a self-assessment scale.
The most common side effects experienced by children and adults who used amifampridine were a burning or prickling sensation, abdominal pain, indigestion, dizziness, and nausea. Side effects reported in pediatric patients were similar to those of adults; seizures have been observed in patients without a history of seizures.
Managing Editor John Gever contributed to this article.