By Debbie Strickland
Special To BioWorld Today
Aviron officials plan to file a biologics license application this fall for FluMist following the success of their largest Phase III trial in adults to date, a study of 4,561 people who received the nose-spray vaccine for the 1997-98 influenza season.
The request for approval will be the second for FluMist. The initial application was not accepted for filing last September.
The FDA did not question the safety or efficacy data, but wanted to see evidence of equivalence between vaccine produced for the clinical trials and vaccine produced at a new Philadelphia plant dedicated to making commercial quantities. Aviron successfully completed a bridging study in March that addressed the issue, and "we're quite comfortable with the results," said Fred Kurland, senior vice president and chief financial officer at the Mountain View, Calif.-based company.
The company is now completing process validation and tying up other loose ends in preparation for the biologics license application (BLA). "The absolute focus at Aviron is to assure that the filing that is made to the FDA is an A-plus filing," Kurland said.
As for the previous BLA, Kurland said, "With 20/20 hindsight, we shouldn't have filed. We should have waited until we had a more complete package."
Results of the latest study will be incorproated into the application, which is expected to be filed in the fall, he said.
In the double-blind, placebo-controlled study, FluMist reduced several illness measures in adults aged 18 to 65: days of febrile illness by 22.9 percent, days of severe febrile illness by 27.3 percent, and days of upper respiratory tract illness by 24.8 percent. The data were published in the July 14 issue of the Journal of the American Medical Association in an article titled, "Effectiveness of Live, Attenuated Intranasal Influenza Virus Vaccine in Healthy, Working Adults." The lead author is Kristin Nichol, chief of medicine at the Minneapolis Vetarans Affairs Medical Center.
The product also aced endpoints designed to measure economic benefits. Over the course of the study, FluMist-vaccinated patients missed 28.4 percent fewer work days due to febrile upper respiratory illness and made 40.9 percent fewer healthcare provider visits. Their use of prescription antibiotics for febrile upper respiratory illness was 45.2 percent less than the placebo arm's, as measured by days of use, and use of over-the-counter medication was 28 percent less.
Trial Designed With Market In Mind
The Phase III trial in working adults, unlike Aviron's previous Phase III studies, did not use clinical confirmation of influenza infection as a primary endpoint. Instead, this time the company looked toward the post-approval marketplace, where cost-benefit analyses will help determine whether the vaccine is widely adopted.
"Pharmacoeconomics is becoming a very important aspect of acceptance," Kurland said. Data from this latest trial provide "building blocks for the kind of cost-benefits analyses that payers of healthcare are going to be interested in as they go through the decision-making process. We want to help people make that decision."
Kurland noted that "every Fortune 500 company has a flu vaccine program now, and we want to be able to add to their armamentarium."
Analysts Felicia Reed and Bill Tanner, of SG Cowen Securities Corp. in Boston, in a research report pegged the product's potential at more than $500 million, with 2000 sales estimated at $163 million, if the product is approved in time for the 2000-01 flu season. The analysts were pleased with the JAMA data and an enthusiastic editorial on the product, but did express some concern about Aviron's pushing the expected filing date decisively to fall, a slight shift from the company's earlier anticipation of a late summer or fall filing.
The JAMA editorial cited by the analysts supports the concept of an intranasal vaccine. The piece is co-authored by Gregory Poland of the Mayo Medical School and Foundation in Rochester, Minn., and Robert Couch of the Baylor College of Medicine in Houston, who wrote, "Perhaps truly effective control of this challenging problem is a realistic goal for the early years of the next millennium." They note that 70 percent of trial participants self-administered FluMist.
A vaccine that is painless, easily obtained, and that does not require a health professional for administration would make widespread immunization of school-aged children - "the most efficient transmitters of the disease" - more convenient, the authors said.
Aviron shares U.S. marketing rights with FluMist collaborative partner Wyeth Lederle Vaccines, a business unit of Wyeth-Ayerst Laboratories, which committed up to $400 million to the project in a deal signed earlier this year. Wyeth Ayerst's parent company is American Home Products Corp. (See BioWorld Today, Jan. 13, 1999, p. 1.)