FDA Approves Use Of Fluarix Under An IND; GSK To Submit BLA In First Half ’05

GlaxoSmithKline plans to establish a presence in the U.S. influenza vaccine market with a BLA submission for Fluarix in the first half of 2005.

In partnership with the National Institute of Allergy and Infectious Diseases, GSK is launching a Fluarix Phase III trial before the end of the year.

The trial will evaluate approximately 1,000 patients between the ages of 18 and 64 years at four centers in the U.S. Eighty percent of subjects will receive Fluarix; the rest will receive placebo.

The objective of the trial is to evaluate the immunogenicity and safety of Fluarix, GSK said. Immunity will be assessed at baseline and three weeks after receiving either Fluarix or placebo.

GSK expects results from the one-month trial to support the BLA filing, suggesting that the company will be seeking licensure via the accelerated approval process.

A Feb. 1 Fluarix BLA submission would set an estimated FDA action date of Aug. 1 under a priority review schedule.

Assuming the Fluarix Phase III trial data are positive, FDA is likely to approve the vaccine quickly.

The agency has been "aggressively" seeking out flu vaccine manufacturers to enter the U.S. market, FDA Acting Commissioner Lester Crawford said during a Dec. 7 teleconference.

"This is not something FDA can readily control," Crawford said. "Nonetheless, a commitment to work with them towards getting an application through the process and approved for that product in the U.S. is something we've been aggressively doing."

FDA took a significant first step in adding U.S. vaccine suppliers Dec. 7 by approving use of Fluarix in the U.S. immediately under an IND.

FDA and HHS have been scrambling to find additional flu vaccine doses and manufacturers for the 2004-2005 flu season following Chiron's announcement that it would be unable to provide its Fluvirin to the U.S. this year, effectively halving the nation's flu vaccine supply (¹ (Also see "Flu Vaccine Shortage Shows Hazards Of Market Concentration – Sen. Leahy" - Pink Sheet, 11 Oct, 2004.), p. 31).

HHS is purchasing 1.2 mil. doses of Fluarix that are available this month, Secretary Tommy Thompson said. A quarter of a million are "in hand," and the remainder will be delivered by year-end.

The additional 1.2 mil. doses bring the nation's flu supply to 62.2 mil. doses, which includes about 58 mil. doses of Sanofi-Aventis' Fluzone and 3 mil. doses of MedImmune's FluMist . GSK has agreed to produce up to 4 mil. doses of Fluarix available this year.

HHS will purchase the Fluarix doses directly from GSK at $7 per dose, which translates to $8.4 mil. in revenue for the already-purchased doses and the potential for a total of $28 mil. if all 4 mil. doses are purchased.

Those figures represent only a fraction of GSK's worldwide sales of Fluarix. However, GSK's use of the IND route this year should give the company a clear path to establishing a more significant market in 2005-2006.

FDA is unlikely to deny approval of the Fluarix BLA after allowing GSK to sell the vaccine under an IND.

"We're confident that the GSK vaccine is safe and effective for use under an IND. This vaccine has been licensed for use in more than 30 different countries," HHS Secretary Tommy Thompson said.

Use of Fluarix in the U.S. under an IND may provide GSK with additional data that could be used as confirmatory data or to bolster its BLA filing.

Under the IND, GSK must "monitor the use of Fluarix, maintain adequate records, control the product supply and provide periodic safety reports to the FDA," HHS said. Patients who receive Fluarix under the IND will be required to complete an informed consent form.

FDA is also in negotiations with "two other vaccine manufacturers, one in Canada and one in Switzerland," about the possibility of purchasing additional flu vaccine doses for this year, Crawford said.

Canadian firm ID Biomedical announced that it would sell its remaining 1.2 mil. doses of Fluviral to Canada, which is also experiencing a shortage.

ID Biomedical is preparing a BLA for Fluviral; the company is meeting with FDA in January to discuss the possibility of receiving accelerated approval for the vaccine.

Remarks made by Crawford indicate FDA is likely to approve only one flu vaccine manufacturer next year.

"We're pleased to report there are two companies that have announced this week that they want to enter the U.S. market," Crawford said. "One of those could be in as early as next flu season, the '05 season, the other one will be a bit later, maybe as late as '07....Nonetheless, by '07 it is now expected that we will have a minimum of four suppliers rather than the one that we were forced to deal with this year."

Chiron remains optimistic that it will be able to produce Fluvirinfor the U.S. market next year.

The company expects the U.K.'s Medicines & Healthcare products Regulatory Agency to inspect its Liverpool, England facility by year-end. FDA said it will determine whether the company can produce Fluvirin for next year's season in January (² (Also see "FDA To Determine Flu Vaccine Suppliers For 2005-2006 Season In January" - Pink Sheet, 29 Nov, 2004.), p. 33).

MHRA announced Dec. 8 it had extended its suspension of Chiron's license for an additional three months beginning Jan. 4.

MHRA characterized the extension as a "routine regulatory action to give Chiron more time to carry out the extensive and detailed remedial plan which is now being put in place." The British health authority's website states that "the suspension can be lifted at any time if Chiron is able to satisfy the MHRA that it has rectified the site's problems."

Chiron announced Dec. 10 that FDA issued a warning letter concerning the facility that cites similar observations made in the agency's Form 483. Chiron will submit its response within 15 working days.

Despite the anticipated addition of two flu vaccine manufacturers, Thompson predicted that the health of the U.S. flu vaccine market will ultimately depend on guaranteed purchase by the government.

"I still believe that there's going to have to be some sort of set purchase in the future," Thompson said. "The government is going to have to be the end buyer to make sure that companies are going to stay with this." Thompson is leaving HHS in 2005.