GAITHERSBURG, Md. A government panel on Tuesday flatly rejected ViroPharma Inc.’s application for Picovir, an investigational drug that reduces the duration of a cold by one day.
While the FDA is not bound by the panel’s decision, in a unanimous vote the Antiviral Drugs Advisory Committee recommended that the agency deny marketing clearance for Picovir (pleconaril).
ViroPharma’s stock (NASDAQ:VPHM) was held Tuesday. It ended Monday at $13.41, down 51 cents.
Mark McKinlay, vice president of research and development and a co-founder of ViroPharma, told reporters after the meeting that Picovir is not dead and the company is evaluating its next move.
“We need some time to think about what happened,” he said. “What you heard was a consensus on efficacy, but there are only a few people on the panel who understood respiratory illness. I don’t think efficacy is the issue. The issue is oral contraceptives and drug interaction. We have to meet with the FDA in the next two weeks and decide the next step.”
In the more than 4,000 patients who have taken Picovir over the years, the drug has proven to be safe and effective with few possible side effects, although one of which is an increased risk of unintended pregnancy.
Panel members had concerns about whether Picovir affected the effectiveness of oral birth control pills and they questioned whether back-up birth control would be needed for patients taking Picovir.
McKinlay said the company would begin two Phase I trials to look at Picovir and how it affects oral contraceptives. He said he did not think ViroPharma will have to do additional Phase III trials.
But while McKinlay said efficacy was not an issue, panel members thought differently.
As predicted by analysts, part of the panel’s problem related to Picovir’s slim efficacy. Most colds or more technically, viral respiratory infections (VRI) run five to seven days, and data from ViroPharma’s two large Phase III trials proved that Picovir reduces severity and duration by a day, only if treatment begins within 24 hours of onset.
“There was little data to show efficacy, and I admit, the efficacy was quite modest,” said Brian Wong, a panel member and chief, infectious disease section at VA Connecticut Health Care System in West Haven, Conn. “What we have is a reduction in symptoms of a day or a half a day and that is not robust. Yet, it is efficacious in a small population.”
From a practical standpoint, panel members also criticized Picovir by saying it would be difficult to prescribe.
“I find [treatment within] 24 hours the most troublesome. I guarantee you there’s no way the patient will see a doctor within 24 hours, so that means the patient will have to call the doctor, or they will have to have [Picovir] in the medicine cabinet ready to take it,” said Princy Kumar, a panel member and chief, division of infectious diseases in the department of medicine at Georgetown University Medicine Center in Washington.
And having the product on hand opens up a different can of worms, said Sharilyn Stanley, a panel member and associate commissioner of disease control and prevention at the Texas Department of Heath in Austin. “Then you have a potential for misuse,” she said.
But Robert Atmar, panel member and associate professor of the departments of medicine and molecular virology and microbiology at Baylor College of Medicine in Houston, said issues of misuse and advance prescriptions are “speculation,” adding he didn’t think “we should vote on speculation.”
Despite the skirmishes on the panel, members stuck together in a 15-to-0 vote. The landslide was not predicted by most analysts, who had indicated the vote would be tight.
Mark Augustine, a biotechnology analyst for U.S. Bancorp Piper Jaffray in New York, said Monday that even if the panel rejected Picovir, the FDA would probably approve it. Before the panel, he viewed Picovir as a “significant” product, capable of generating upward of $600 million in worldwide peak sales, with the majority in the U.S. Other estimates have been as high as $900 million to $1 billion annually.
The drug works by inhibiting the ongoing viral replication of picornavirus capsid, a protective shell of the virus that is necessary for infection and transmission. There are no marketed antivirals for the common cold and no vaccine.
The Bethesda, Md.-based National Institutes of Health said 52 million annual physician visits are attributable to the common cold. Statistics released by ViroPharma showed that 30 percent to 50 percent of those visits result in antibiotic prescription. Piper Jaffray’s Augustine said Picovir could have a positive impact on reducing antibiotic over-prescriptions.
About two years ago, ViroPharma’s stock dropped 68 percent (down $48.50, to close at $23.25) on news that a Phase III trial of Picovir failed. The company blamed the failure on variability of the patient population. In the subsequent trials, all participating patients were required to have a mild to severe runny nose, and to avoid products other than Tylenol and Benylin. (See BioWorld Today, April 12, 2000.)
ViroPharma submitted its new drug application for Picovir in July 2001, and received notification in late September that the submission was accepted.
Around that time, Aventis signed on as the U.S. and Canadian partner, providing a $25 million initial payment for ViroPharma plus undisclosed milestones for regulatory and other achievements. Also, the companies agreed to split the profits, with Bridgewater, N.J.-based Aventis getting 55 percent. (See BioWorld Today, Sept. 11, 2001.)
Following the panel Tuesday, McKinlay told reporters that Aventis remains committed to the co-promotion and development deal.
ViroPharma, of Exton, Pa., licensed pleconaril from Paris-based Sanofi-Synthelabo in 1995. After the first Phase III trial failure, the companies renegotiated the original deal, reducing royalty payments due to Sanofi-Synthelabo on U.S. and Canadian sales after selection of a partner. Royalty rates dropped from the mid-teens to low-single digits. Also, ViroPharma’s milestone payment requirements were eliminated. (See BioWorld Today, Feb. 28, 2001.)