By Mary Welch

The FDA informed Aviron its regulatory submission for FluMist, a nasal spray influenza vaccine, is not acceptable for filing because the paperwork lacks manufacturing data.

"We were surprised by the decision," said J. Leighton Read, chairman and CEO of Mountain View, Calif.-based Aviron, noting the FDA did not question the safety or efficacy data for the vaccine.

The company's stock (NASDAQ:AVIR) fell more than 40 percent Tuesday, closing at $12.50, down $9.19.

Aviron filed its product license application/establishment license application in late June, citing studies in children, adults and the elderly.

The FDA's decision poses a "significant risk to the launch," planned for 1999, Read said.

"We had anticipated a request for further information, but some of it couldn't be obtained in time [for] our filing in June," he told BioWorld Today. "After a careful evaluation, we made the decision to proceed and felt we could provide the information during the process."

Aviron officials will meet with the FDA shortly, and the company could refile as early as October.

The bulk vaccine for the clinical trials was manufactured by Medeva Pharma Ltd. (formerly known as Evans Medical), of Liverpool, U.K. The scale-up commercial formulation will be blended, filled, packaged, labeled and stored at Packaging Coordinators Inc. (PCI), in Philadelphia, which this year opened a 34,000-square-foot plant dedicated to producing FluMist.

"The FDA is seeking clarification about the consistency between the Medeva Pharma operations and the PCI facility," Read said.

Aviron's quest is for approval of FluMist to prevent influenza and its complications in both adults and children. In addition, the company seeks an indication for FluMist when co-administered with the flu shot for high-risk adults, such as the elderly.

"I've told our investors that when a vaccine is intended for widespread use in healthy people, the vaccine deserves to be scrutinized carefully," Read said. "We have no problems with what the FDA is asking for."

Before approval, the FDA could demand another trial to validate the commercial production process at PCI.

"We are prepared to do that and will talk with the FDA about that," Read said. Such a trial would take at least six months. Additional stability data could also be required. The delay would "significantly reduce the chance that FluMist would be approved in time for the 1999-2000 flu seaso,." he said.

FluMist is a cold-adapted trivalent vaccine containing two different influenza A strains and one influenza B strain, selected each year based on worldwide surveillance. The internal flu proteins from these master strains of influenza A and B virus grow at cooler temperatures and combine with hemaglutinin and neuraminidase, the surface proteins found on contemporary circulatory viruses. FluMist stimulates the mucosal immune system as well as the systemic immune system, resulting in a strong cytotoxic T-cell response. (See BioWorld Today, July 2, 1998, p. 1.) *