to make doctors and patients aware of pseudobulbar affect – not to mention Zenvia itself – if the drug is eventually approved. As a start, the company created a PBA website with information about the disorder and the ongoing study.
What causes PBA isn’t certain. Wynn said some researchers suspect lost connections between the brain stem, which is responsible for emotional reactions, and the frontal lobe, the decision-making area of the brain. Some doctors prescribe antidepressants or antipsychotic drugs for PBA but no controlled studies have been conducted to show those medications work. There are no FDA-approved drugs for PBA, a condition that affects 1.8 million with brain injuries or neurological diseases, according to Avanir. The figure includes 15 percent of people with brain injury, four percent of people with stroke, three percent of people with Parkinson’s disease, 10 percent of people with multiple sclerosis, and nine percent of those with Alzheimer’s disease or dementia.
Zenvia is a combination of two generic drugs. Dextromethorphan, the active ingredient, is found in over-the-counter cough medicine. The second drug, quinidine, is a heart drug that increases the effect of dextromethorphan. DMQ was developed in the 1990s to slow the progression of ALS. Clinical studies showed it had no effect on the natural course of the illness, but patients and their caregivers kept asking for the drug because it reduced bothersome emotional outbursts. That unexpected finding led to Avanir’s current development program.
Avanir, which was founded in San Diego as Lidak Pharmaceuticals, has conducted two late-stage trials. In a study of 140 patients with ALS that was completed in 2002, those on DMQ had a 50 percent drop in PBA symptoms compared to those given either dextromethorphan or quinidine. A study of 150 multiple sclerosis patients completed in 2004 found about a 60 percent decline in PBA symptoms compared to a placebo. The most common side effects found in the clinical studies were nausea (22 to 33 percent of patients), dizziness (20 to 26 percent) and fatigue (14 to 19 percent). The drug also caused changes on electrocardiograms, raising concerns that some patients might experience abnormal heart rhythms on the medication.
Katkin said the FDA was concerned that forgetful patients might accidentally repeat a dose and get into trouble.
In the study now underway, patients are receiving a reformulated DMQ that contains two-thirds less quinidine that the original drug; Katkin said the change should increase the margin of safety for patients who mistakenly repeat a dose. The new formula is expected to retain 75 percent of the efficacy of the original with fewer cases of nausea, dizziness and fatigue. If the trial is successful, DMQ should receive FDA approval during the second half of 2010, Katkin said. At that point, the company may take on a partner to develop the drug for other conditions, such as neuropathic pain or aggression related to Alzheimer’s disease. “It will open up a whole new area,” Wynn said.
Investors have certainly been patient. Avanir has lost more than $250 million since its 1988 inception. Last year, the company’s share price remained below $1 for more than a month, endangering its listing on the global NASDAQ market. Avanir’s stock price has more than doubled lately, buoyed by cautious optimism about the latest clinical trial. Now they’re just hoping the results don’t move them to tears.