Aug 14, 2009
Sponsor Reports Positive Results of Clinical Trial of Zenvia™ for Pseudobulbar Affect (Uncontrollable Laughing and/or Crying)
An oral drug designed to treat uncontrollable laughing and/or crying (also called pseudobulbar affect), a troubling symptom experienced by some people with MS, ALS, and other neurological disorders, has passed another hurdle by showing positive results in a Phase III trial. According to company sources, Zenvia™ (Avanir Pharmaceuticals) significantly reduced the rate of laughing and crying episodes and appeared to be safe and well tolerated. The company is conducting a complete analysis of the results to present at scientific meetings and to prepare a filing with the U.S. Food and Drug Administration requesting approval to market the drug.
Background: A small percentage (10% or less) of persons with MS experience uncontrollable episodes of laughing and/or crying that are unpredictable and seem to have little or no relationship to actual events or the individual’s actual feelings. This condition is thought to result from lesions -- damaged areas -- in emotional pathways in the brain. It is important for family members and caregivers to know this, and realize that people with MS may not always be able to control the expression of emotions. Some medications have shown benefit in small clinical trials, but there is no medication approved specifically to treat this symptom.
Avanir Pharmaceuticals has been conducting trials of Zenvia in its current and related formulations for several years as a treatment for pseudobulbar affect in a number disorders, including MS, ALS, Alzheimer’s disease and stroke. Zenvia is a patented, orally-administered combination of dextromethorphan and an enzyme inhibitor known as quinidine to sustain a therapeutic level of dextromethorphan in the body. In 2006, Avanir received a letter from the FDA indicating that the drug was “approvable” and requesting that additional studies be conducted, leading to the current study.
Study Details: According to a company press release, this trial, called the STAR trial, used a new, lower-dose formulation designed to address some safety issues raised by the FDA. The trial involved 326 individuals (197 with ALS and 129 with MS) across the U.S. and Latin America who were experiencing pseudobulbar affect. Participants either received one of two doses of Zenvia or inactive placebo twice a day for twelve weeks.
The primary endpoint established for this trial was the rate of self-reported laughing or crying episodes over the course of the trial. Both doses significantly reduced episode rates compared to placebo. Those on the higher dose experienced an average of 88% reduction in episode rates compared to their baseline rates before they began treatment. Several other measures were used as secondary endpoints to test the drug’s impact but those results are still being analyzed.
The drug was relatively well tolerated. The adverse events more frequently reported by those on therapy versus those on placebo were dizziness, nausea and diarrhea. There were seven deaths in the study, all occurring in participants who had ALS. One of the deaths, which occurred five days after treatment stopped, was thought to be possibly related to treatment.
Avanir has thus far only released top-line results from this trial, and is conducting a complete analysis of the results to present at a scientific conference. The company anticipates using these and other study results in 2010 to request that the U.S. Food and Drug Administration approve the drug for marketing.
Comment: “The availability of a drug that could safely and effectively treat pseudobulbar affect would be a real breakthrough for those with MS and other neurological conditions who experience this troubling symptom,” said Dr. Nicholas LaRocca, a clinical psychologist who directs the National MS Society’s research programs in patient management and health care delivery and policy.
Read more about MS and emotional changes
Download a Clinical Bulletin for physicians, providing details about pseudobulbar affect and its treatment in MS, from our Professional Resource Center