Washington Editor

The FDA is not expected to grant ViroPharma Inc. regulatory clearance for its cold medicine that has been criticized for reducing the duration of illness by only one day.

ViroPharma, of Exton, Pa., and its partner, Aventis Pharmaceuticals, of Bridgewater, N.J., released a brief statement late Thursday saying the FDA intends to issue a "not approvable" letter by May 31 in reference to the new drug application (NDA) for Picovir.

ViroPharma's stock (NASDAQ:VPHM) took the news hard Friday, falling 92 cents, or 21.7 percent, to close at $3.33. The company's stock was trading at $13.41 in March before the FDA's Antiviral Drugs Advisory Committee voted 15-0 against recommending Picovir (pleconaril). (See BioWorld Today, March 20, 2002.)

Neither company would provide insight into specific concerns that may cause the FDA to reject the cold medicine for use in adults. However, if the agency's questions mirror the panel's, it is likely that the drug's modest efficacy and possible interference with other drugs, including oral contraceptives, were among the points raised.

Kori Beer, ViroPharma's spokeswoman, told BioWorld Today, "We will wait until we get the letter to determine our path forward."

In a similar comment, Aventis spokeswoman Lise Geduldig told BioWorld Today that it is premature to discuss the future of Picovir without seeing the FDA's letter first.

After the letter is issued, the companies will have the opportunity to meet with the agency to resolve the problems.

In September, Aventis and ViroPharma signed a partnership covering the U.S. and Canada. Aventis paid $25 million up front and is responsible for undisclosed milestones related to regulatory approval and other achievements. Picovir profits are scheduled to be split 55-45 percent in Aventis' favor. (See BioWorld Today, Sept. 11, 2001.)

Beer said this event has no impact on the Aventis contract.

While the partners wait for an official government letter, research notes released by Jeffrey Stevens, an analyst at J.P. Morgan Securities Ltd. in London, said the firm is removing all Picovir sales from the Aventis model. Indeed, J.P. Morgan had projected only modest sales of Picovir, but other estimates from U.S. analysts had projected sales as high as $600 million at peak.

Picovir works by inhibiting the ongoing viral replication of picornavirus capsid, a protective shell of the virus that is necessary for infection and transmission.

Even though both companies were tight-lipped Friday, following the FDA meeting back in March, ViroPharma officials were optimistic, blaming the negative vote on the panel's failure to understand respiratory illness.

In a press conference with reporters after the rejection, Mark McKinlay, vice president of research and development and a co-founder at ViroPharma, told reporters that the panel appeared to be more concerned about possible drug interaction and unintended pregnancy than efficacy.

Even if that's true, Picovir's efficacy is described by most as modest because it reduces severity and duration of cold symptoms by only a day. Furthermore, the product must be taken within 24 hours of the onset of cold symptoms.

ViroPharma conducted two randomized, placebo-controlled trials that enrolled a total of 2,096 patients. In the five-to-seven-day treatment group, two women in the Picovir group became pregnant, but neither was taking oral contraceptives. In the six-week study, six women in the Picovir group became pregnant, including two who were taking oral contraceptives. Sixty-eight percent of participants in the primary analysis group were women.

Two Phase I trials to determine the impact of Picovir on oral contraceptives are under way.

This recent bout of bad news doesn't mark the first time Picovir has caused some trouble for ViroPharma.

Two years ago, the company's stock dropped 68 percent (down $48.50, to close at $23.25) on news that a Phase III trial of the cold drug had failed. The company blamed it on variability of the patient population. (See BioWorld Today, April 12, 2000.)

ViroPharma 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.)