By Lisa Seachrist
WASHINGTON - After equivocal results from the first leg of a four-part Phase III clinical program testing pleconaril for the treatment of pediatric viral meningitis, ViroPharma Inc. said the drug proved effective in the program's second leg, treating the disease in adults.
Exton, Pa.-based ViroPharma said pleconaril relieved the headache associated with viral meningitis more quickly than placebo in a clinical study of 130 adults. Two ongoing adult and pediatric clinical studies are expected to be completed mid-year.
"Patients treated with pleconaril had headache relief within 24 hours of being treated," said Kori Beer, director of corporate communications for ViroPharma. "Currently, there is no treatment for viral meningitis. We hope to file a new drug application with data from all four trials sometime this year."
Pleconaril is an oral liquid formulation of an active inhibitor of picornaviruses - the RNA viruses responsible for the majority of all human viral illnesses, ranging from severe illnesses to common maladies. Picornaviruses cause viral meningitis; viral inflammation of the heart; neonatal enteroviral disease; viral respiratory infection; and the common cold.
Drug Stops Essential Viral Enzymes
Pleconaril stymies picornaviruses by inhibiting the enzymes essential for the viruses' replication. Because picornaviruses grow by replicating RNA - a process different from the survival cycles of DNA viruses, retroviruses and cells - pleconaril is a specifically targeted drug, with few side effects.
Viral meningitis causes a severe headache, stiff neck, fever, muscle pain, nausea, vomiting and malaise. For 25 percent of all patients, the illness lasts for over two weeks. There are currently no antiviral medications to treat viral meningitis, and therapies are palliative.
In November, the company's stock plummeted 40 percent after the preliminary data from a pediatric study of the drug indicated it had failed to meet its primary endpoint: reduction in headache. However, the drug met all of its secondary endpoints. (See BioWorld Today, Nov. 6, 1998, p. 1.)
Harley Rotbart, professor and vice chairman of pediatrics at the University of Colorado School of Medicine, in Denver, said monitoring headache relief in children proved more difficult than the researchers had anticipated, because children may experience or identify headache differently from adults.
The adult study of pleconaril compared 130 adults with viral meningitis, treated with either 200 milligrams of pleconaril or placebo. The median duration of headache for pleconaril-treated patients was reduced by two days in patients with confirmed enteroviral meningitis, and by one day in all randomized patients. Both of the endpoints were statistically significant.
Seventy-five percent of all pleconaril-treated patients achieved the primary endpoint of headache relief in four days, whereas placebo-treated patients reached that endpoint in seven days.
"This would be a very welcome addition to what we can do for patients with enteroviral meningitis," Rotbart said.
ViroPharma also has ongoing Phase II studies in viral respiratory infections, of which the common cold is one type. A compassionate-use study is under way in chronic meningoencephalitis. In the preclinical stage are compounds for hepatitis C and respiratory syncytial virus.
ViroPharma's stock (NASDAQ:VPHM) closed Wednesday at $12.50, up $2.50. *