A complete response letter from the FDA regarding FluMist has elicited a positive reaction at MedImmune Inc., which also reported record revenue as part of its fourth-quarter and year-end earnings.

"What a year, what a quarter, and in fact, what a day," MedImmune CEO and Vice Chairman David Mott said during a conference call. "Over the past year we've transformed our relationship with the FDA on this product."

Importantly, the agency did not request additional clinical trials of the live influenza virus vaccine, a nasally delivered product that has been dogged by questions surrounding prior applications. The five-question letter, received a month earlier than expected, seeks clarification and additional information relating to data previously submitted by the Gaithersburg, Md.-based company.

"We do not view any of these as particularly difficult or as impediments to licensure," Mott said, adding that MedImmune would respond within a week.

Jamie Lacey, MedImmune's associate director of public relations, told BioWorld Today that one question centered on submitting the data specific to initial labeling for the 5- to 49-year-old population, a second addressed proposals for post-marketing studies and the remainder dealt with technical clarifications on assays and testing issues.

"But there weren't any further issues related to the last complete response letter," she said. "These are relatively minor outstanding issues."

Mott said MedImmune expects to receive approval in the second quarter, a near-term positive for a drug that has followed a bumpy road en route to possible approval.

Last month, the FDA's Vaccines and Related Biological Products Advisory Committee voted favorably on the questions of safety and efficacy for FluMist in preventing influenza in healthy people between the ages of 5 and 49. A majority of the 18-person panel also voted FluMist safe in the 50- to 64-year-old population, but only four agreed that it was efficacious in that group. (See BioWorld Today, Dec. 18, 2002.)

Beyond working toward approval in the 5- to 49-year-old age group, Lacey said MedImmune's next priority would be to seek an added indication for the older set.

"Based on feedback from the panel, the idea is for us to test more individuals," she said. "That seemed to be the biggest concern - that we had a small number within that age cohort."

Though the final protocol has yet to be established with the FDA, MedImmune indicated that additional placebo-controlled studies would begin late this year and continue during the 2003-04 flu season. Additional studies for younger patients - between 19 months and 4 years old - could involve safety and efficacy endpoints and take a year longer, Lacey said.

The FDA is not bound by the panel's decision, but prior biologics license applications for FluMist have run into trouble during panel presentations. The original application was submitted in October 2000 by Mountain View, Calif.-based Aviron Inc., acquired by MedImmune a year ago in a $1.5 billion merger. (See BioWorld Today, Dec. 4, 2001.)

An earlier panel voted 13-2 in favor of the drug's efficacy in 18- to 64-year-old healthy people, though it was split (8-7 against) in 1- to 17-year-olds. But a lack of safety data proved a more significant problem. The panel voted 9-5 that safety data were insufficient in 1- to 64-year-olds. (See BioWorld Today, July 30, 2001.)

MedImmune then dealt with two subsequent complete response letters from the FDA - the company submitted answers in August 2001 and July 2002.

If approved, MedImmune said FluMist would be the first and only intranasal influenza vaccine in the U.S. It contains three strains of live, attenuated, cold-adapted, temperature-sensitive influenza virus: two Type A (H1N1 and H3N2) and one Type B. As part of an ongoing global collaboration agreement, MedImmune and Wyeth Pharmaceuticals would market the drug. The deal with the division of Madison, N.J.-based Wyeth was inherited in the Aviron merger.

Lacey said MedImmune intends to market FluMist for the coming flu season, which the company projects could add between $120 million and $140 million to its 2003 revenue.

MedImmune on Thursday also reported a 37 percent increase in year-end revenue for the period ended Dec. 31. It registered quarterly earnings of $85 million despite a year-end loss of $1.1 billion. Included in the loss is MedImmune's purchase price of Aviron - now called MedImmune Vaccines - as well as the inclusion of the latter's operations in the former's results as of Jan. 10, 2002. MedImmune in 2001 reported $149 million in year-end earnings.

Its fourth-quarter earnings were driven in large part by a spike in worldwide sales of Synagis (palivizumab). Total quarterly revenues totaled $382 million, of which $312 million is attributed to Synagis - a 25 percent increase to the comparable year-earlier quarter. Year-end revenues reached $848 million, including $668 million in Synagis sales - a 29 percent increase over 2001.

For the end of the year, MedImmune reported cash and marketable securities of $1.4 billion.

"From our vantage point the numbers are positive," Lacey said. "Two thousand and two was a year in which we were building for the future, and I think we made a lot of progress on that front. Two thousand and three will see continued progress."

The company's plans for pipeline expansion include a fourth-quarter initiation of Phase III studies of a human papillomavirus vaccine in collaboration with London-based GlaxoSmithKline plc. Mott said a Phase II trial of the vaccine to prevent cervical cancer recently was unblinded, with results to be presented at April's Eurogen meeting in Paris.

Mott pointed to progress from another vaccine, Vitaxin, which he said MedImmune plans to advance to Phase II studies this summer in cancer and rheumatoid arthritis patients.

Lead molecules have been selected for development and preclinical testing is near completion for a pair of products - an IL-9 antagonist to treat asthma and Numax, a next-generation respiratory syncytial virus antibody. Mott said MedImmune expects to file investigational new drug applications to advance both products into clinical trials during the third quarter.

MedImmune's stock (NASDAQ:MEDI) rose $1.96 Thursday, closing at $29.86.