Editor

Talk about a shot in the arm (or a squirt up the nose): The ailing biotechnology sector got a boost last week when FDA advisory panels gave their blessings to a pair of potentially important but historically beleaguered drugs - Corixa Corp.'s Bexxar for non-Hodgkin's lymphoma and MedImmune Inc.'s FluMist, a nasal influenza vaccine.

Wall Street had been cautiously optimistic about both, but it was Bexxar (tositumomab), an antibody specific to the CD20 antigen on B cells conjugated to radioactive iodine-131, that hit the home runs.

Bexxar, partnered with GlaxoSmithKline plc, won a 10-3 nod for low-grade or transformed low-grade NHL from the Center for Drug Evaluation and Research's Oncologic Drugs Advisory Committee, and a 13-0 vote in favor of the drug for follicular NHL that has relapsed after chemotherapy and is refractory to Rituxan (rituximab), the non-radiolabeled chimeric antibody against CD20 from Genentech Inc. and IDEC Pharmaceuticals Corp.

This means Bexxar is probably in line for at least one of the two sought indications - that is, for accelerated approval in relapsed or refractory low-grade or transformed low-grade NHL, and/or for Rituxan-refractory disease. As with FluMist, the Bexxar development has been long. The biologics license application for the latter drug was submitted in June 1999.

IDEC also has Zevalin (ibritumomab tiuxetan), the first radioimmunotherapy in the U.S., which surged ahead of Bexxar to win approval in February. It's a monoclonal antibody linked to the radioisotope yttrium-90 that also targets the CD20 antigen. Zevalin is indicated for relapsed or refractory low-grade, follicular or transformed B-cell NHL cases, including the Rituxan-refractory follicular ones.

A problem for Zevalin has been - and for Bexxar may be - the increasingly solid, extended data for Rituxan against NHL, some of which were presented earlier this month by Genentech at the 44th annual meeting of the American Society of Hematology in Philadelphia.

The trial tested Rituxan in patients with indolent non-Hodgkin's lymphoma and showed that single-agent Rituxan therapy reduced the risk of disease progression or relapse by 55 percent for responding patients and nearly doubled event-free survival for chemotherapy-naive indolent NHL patients.

Physicians apparently are questioning why they should use a blood-circulating radioactive drug when Rituxan is working, and Wall Street projections of Zevalin sales for 2003 already have been lowered, analysts point out.

FluMist's situation with its panel was somewhat more complicated than Bexxar's. Rather than vote on whether to recommend it for approval, the Vaccines and Related Biological Products Advisory Committee cast ballots on whether the drug was safe and efficacious in three age groups: 5 to 17, 18 to 49 and 50 to 64.

The panel voted positively on safety in the 5-to-17 and 18-to-49 groups, with only one negative ballot in each, and in the 18-to-49 group, where the favorable vote was 10-8.

For efficacy, the vote was positive in the 5-to-17 and the 18-to-49 groups, but negative in the 50-to-64 group, where the committee voted 14-4 against recommending approval because of insufficient data.

Caroline Copithorne, analyst with Morgan Stanley, examined FluMist's prospects in a research note titled "Don't Be Sad, 'Cause Two Out of Three Ain't Bad" - perhaps the first time such a report's headline has included the lyrics to a rock song by Meat Loaf.

Copithorne told BioWorld Financial Watch that a positive panel vote in the 50-to-64 group would have been gravy but is "not the key for this particular product."

She said the age group is "certainly important because they're the most likely to get vaccines, and they're the ones for which [vaccines are] recommended," and MedImmune and FluMist partner Wyeth have a good chance of winning that indication from the FDA in the end. She put the odds at 75 percent to 80 percent.

"Unlike the 5 and under [population group] where they've identified specific issues, in the 50-to-64 group there was no evidence of any problem," she said, and the companies lacked data in that segment partly because the older population is one in which "you get proportionately fewer patients" when designing trials.

There might have been another reason, too, Copithorne said.

"One person [on the committee] mentioned that the population that included that group had been voted for favorably for efficacy in the first panel meeting, and that may be why they didn't target additional trials" in the older population before the most recent panel meeting, she said.

What's more, a panel member noted that a live attenuated vaccine such as FluMist might better serve the older population, since this is the group that often loses its responsiveness to inactivated vaccines.

"Given that, and the fact that they voted favorably for safety even on this panel," the chance of an ultimate label for the indication seem high if more data are gathered, Copithorne said. She put the possibility of an approval in the older patient group otherwise at "less than 50 percent."

MedImmune also has on the market Synagis (palivizumab) to prevent respiratory syncytial virus in pediatric patients at high risk; Ethyol (amifostine), a selective cytoprotective agent used to reduce some toxicities associated with cancer chemotherapy and radiotherapy; and CytoGam, an intravenous immune globulin indicated for prophylaxis against cytomegalovirus disease associated with the transplantation of a kidney, lung, liver, pancreas or heart.

Copithorne estimated approval at least in some indications for FluMist - the biologics license application for which was submitted in October 2000 - "well ahead of the 2003-2004 flu season," with more guidance forthcoming by the FDA deadline of Feb. 27, 2003, under the Prescription Drug User Fee Act. The deadline under PDUFA for a Bexxar decision is May 2.