In clinical trials, Nuedexta was safe, reduced the frequency and severity of PBA episodes, and showed a significant advantage over a placebo. But in 2006, the FDA expressed concerns that higher doses of the drug combination raise the risks of dangerous cardiac rhythms. By reducing the doses of quinidine from 30 milligrams to 10 milligrams, Avanir satisfied the FDA's concerns about cardiac risks. In a Phase III clinical trial of the drug with MS patients, half the study participants who got the drug reported no PBA episodes in their last two weeks of the study.
"This is wonderful news for all the patients who suffer from PBA," said Dr. Erik Pioro, a Cleveland Clinic neurologist who specializes in ALS and related disorders, moments after hearing of the FDA nod. "They will now have an effective, safe, and well-tolerated treatment for this distressing and extremely isolating condition."
In the absence of something better, doctors have treated PBA with off-label prescriptions for antidepressants or levodopa, which boosts levels of the neurotransmitter dopamine. But these have a range of side effects and haven't been subjected to large studies in PBA patients.
Diehl has been among those taking antidepressants to help with the laughing and crying, even though he's not clinically depressed. But he's excited at the prospect of being able to take one pill, Nuedexta, instead of three for PBA. In fact, during a family dinner on Sunday night, his older daughter heard her father becoming overly animated during a discussion and asked aloud, "When is that drug going to be available?" Arlene Diehl recalled. "She was in a kind way saying to her father, 'you're overreacting and we're anxious for you to get on that drug.'"
David Diehl already knows something about Nuedexta, because at the suggestion of his neurologist, he participated in one of the studies that ultimately led to FDA approval. During that trial, in which some patients got the medication and others got a placebo, all patients subsequently had the option of taking the drug. Diehl believes it helped him, and said, "With this drug, there was no downside. This was the only drug I've ever taken where there were no side effects for me."
The most common side effects reported in clinical trials were falling, dizziness, headache, nausea and diarrhea.
Avanir plans to make the drug available in the first quarter of 2011, said CEO Keith Katkin, and will start by providing 30-day samples to select doctors who treat PBA. In an interview Monday, Katkin said the drug is taken once daily for the first seven days; and then twice daily. Avanir estimates the drug will run $3,000 to $5,000 a year, or about $250 a month. To assure that all patients who want the drug can get it, Avanir is establishing a co-payment assistance program capping the maximum amount that qualifying patients pay out-of-pocket.
Other patients with limited incomes will get the drug free through a patient assistance program, Katkin said. "These patients have stood by us through our clinical studies. We could not have made it to where we are at without them... if they qualify on the criteria, then they have access to free product for as long as they want to have and receive a prescription for it."