By Charles Craig
MedImmune Inc., whose shares soared Wednesday on release of positive Phase III trial results for its antibody against respiratory syncytial virus (RSV) in infants, said it expects to file a biologics license application (BLA) with the FDA for the drug by the end of 1997.
In a placebo-controlled clinical trial enrolling 1,500 children at risk of developing life-threatening RSV, treatment with MedImmune's humanized monoclonal antibody, MEDI-493, reduced hospitalizations associated with the disease by 55 percent -- a statistically significant finding in the study's primary endpoint.
MedImmune's stock (NASDAQ:MEDI) jumped $5.312 Wednesday, closing at $24.937.
RSV is a leading cause of pneumonia and other respiratory ailments, such as bronchiolitis, in infants and children. The seasonal virus can be life-threatening for high-risk infants, who are defined as those born prematurely and those with bronchopulmonary dysplasia (BPD). RSV sends about 90,000 high-risk children to the hospital each year and kills 4,500 of them.
MEDI-493 is the second RSV drug developed by MedImmune, of Gaithersburg, Md. The first, RespiGam, is a polyclonal antibody derived from donor blood and was approved by the FDA in January 1996.
In data supporting RespiGam's approval, treatment with the immunoglobulin reduced RSV-related hospitalizations by 40 percent.
MEDI-493 is considered more potent, easier to make, and more convenient to administer than RespiGam, which is infused over two to four hours in a hospital and whose production is limited by the supply of donor blood.
MEDI-493 is given intramuscularly in a single injection in a doctor's office once a month during the six-month RSV season between November and April.
MedImmune has said it will continue to market RespiGam. The clinical trials showed that RespiGam, in addition to reducing RSV-related hospitalizations, was effective in preventing other infections because of the variety of antibodies in the donor blood. However, if MEDI-493 makes it to market, it is expected eventually to replace RespiGam.
The Phase III trial of MEDI-493 was conducted at 139 medical centers in the U.S., Canada and the U.K. Prematurely born infants and children less than two years old with BPD received either the monoclonal antibody or a placebo in monthly injections between November 1996 and April 1997. About 1,000 youngsters were given MEDI-493 and 500 a placebo.
The drug not only reached its primary goal of preventing hospitalizations, but also achieved secondary endpoints demonstrating MEDI-493 reduced the severity of RSV for those children who were hospitalized.
MedImmune said adverse reactions were similar in both the treatment and placebo groups. Fatalities in the MEDI-493 group numbered four of 1,002 children, compared with five of 500 in the placebo group. The company said the deaths were consistent with the children's underlying condition, either BPD or premature birth. None of the fatalities in the treatment group was attributed to MEDI-493.
MedImmune expects to file for regulatory approval of MEDI-493 in Canada and Europe during 1998.
If MEDI-493 makes it to market, it would be the first monoclonal antibody approved for an infectious disease. The antibody is designed to block viral protein essential for the infection of cells.
Some Wall Street analysts have projected annual U.S. revenues of about $250 million to $300 million for MEDI-493, which would be three times higher than RespiGam's estimated sales.
MedImmune copromotes RespiGam in the U.S. with its partner, American Home Products Corp., of Madison, N.J. Baxter Healthcare Corp., of Deerfield, Ill., has marketing rights to RespiGam outside North America.
MedImmune developed MEDI-493 on its own, having regained all rights to the drug in 1995 from American Home Products. Clinical development of the drug cost the company between $30 million and $40 million.
Mark Kaufmann, MedImmune's associated director of strategic planning and investor relations, said the company will market MEDI-493 in the U.S. with its established RespiGam sales force, if the drug is approved, and likely will seek a partner for sales outside North America.
Sales of RespiGam in the fourth quarter of 1996 totaled $13.9 million, and $5.2 million in the first quarter of 1997, Kaufmann said.
Prior to RespiGam's clearance, the only FDA-approved treatment for RSV was the antiviral agent ribavirin, or Virazole, made by ICN Pharmaceuticals Inc., of Costa Mesa, Calif.
Another biotechnology company, OraVax Inc., of Cambridge, Mass., was developing a monoclonal antibody, called HNK20, for RSV, but in March the release of Phase III trial data showed the treatment failed to achieve its primary endpoint of reducing hospitalizations. HNK20, administered in nose drops, was designed to stimulate immunoglobulin A antibodies of the mucosal immune system to prevent infections.
SmithKline Beecham plc, of London, suspended development in 1996 of its monoclonal antibody against RSV after it failed to demonstrate efficacy in Phase III trials. *