FDA DELAYS APPROVAL FOR PSEUDOBULBAR AFFECT DRUG
The FDA has delayed approval for an experimental treatment for involuntary emotional expression disorder (IEED), or pseudobulbar affect (emotional lability), citing the need for more data. Avanir, which markets the drug AVP-923 as Zenvia, had submitted a new drug application in January, and will be meeting with the FDA to discuss data needed for approval. In an Oct. 31 news release, however, the company said it was not certain that once it has met with the FDA, that it will continue developing the drug.
The central agent of the drug is dextromethorphan, an antiexcitatory glutamate inhibitor, which is combined with quinine to enhance bioavailability. Quinine acts by inhibiting cytochrome P450, which metabolizes dextromethorphan, resulting in blood levels that allow the drug to cross the blood-brain barrier. The effect on emotional lability was noted when the combination therapy was used in a therapeutic trial of amyotrophic lateral sclerosis (ALS).
IEED is characterized by involuntary crying, laughing, or both, and occurs with several neurological disorders, including multiple sclerosis, Alzheimer disease, stroke, Parkinson disease, ALS, and traumatic brain injury. “IEED is a surprisingly disabling disorder that can interfere with normal social interactions and personal relationships,” Hillel Panitch, MD, Professor of Neurology at the University of Vermont in Burlington, told Neurology Today in an interview.
Dr. Panitch led a three-month, double-blind, placebo-controlled study of AVP-923 that found the drug effective and safe for treating pseudobulbar affect in MS patients (Ann Neurol 2006;59:780–787). Patients filled out questionnaires to rate the frequency of uncontrolled laughing and weeping episodes, as well as quality of life and relationships. Patients who took AVP-923 had significantly fewer episodes of laughing and crying (a 46 percent reduction), and improved quality of life. Dr. Panitch said he has not observed any serious adverse effects among his patients.
When asked to comment why AVP-923 was not approved yet, the FDA would not provide specific details. Dr. Panitch suggested, however, that the agency is requesting additional efficacy and safety information, and possibly additional clinical trials, before granting approval.
“This is disappointing, not only to me and to the other investigators, but to the thousands of patients with neurological diseases who may benefit from treatment,” he added.