MedImmune Inc., with positive data from one Phase IIItrial and disappointing results from another study, saidWednesday it will use both sets of findings to support asecond attempt at getting FDA approval of Respigam, animmunoglobulin drug for respiratory syncytial virus(RSV) in infants.
In December 1993, the FDA's Blood Products AdvisoryCommittee rejected Respigam, which was then calledRespivir, and recommended more studies for thepolyclonal antibody. MedImmune had filed a productlicense application (PLA) in 1992.
The Gaithersburg, Md.-based company Wednesdayreleased results of two additional Phase III trials, whoseprimary endpoint was preventing infants at high risk ofgetting RSV from developing a serious infectionrequiring hospitalization.
In one 510-patient study, called the Prevent trial,Respigam achieved statistical significance in reducingRSV-related hospitalizations. But in a second 429-patientstudy, called the Cardiac trial, the drug did not reach thatsame level of efficacy.
David Mott, MedImmune's executive vice president, saideven though statistical significance was not achieved inthe Cardiac trial, "there was a reduction in RSVhospitalizations" with Respigam.
Mott said he could not provide details from either trialprior to the FDA reviewing the results. The data will besubmitted as an amendment to the original PLA.
Despite MedImmune's positive interpretation of theRespigam studies, Wall Street was unimpressed. Thecompany's stock (NASDAQ:MEDI) declined $2.75 to$9.25, a 23 percent decline.
Timothy Wilson, an analyst with Hambrecht & Quist Llcin New York, said that among the reasons forMedImmune's drop was failure of Respigam to achievestatistical significance in the Cardiac trial. Another factor,he said, was lack of specific data on the two trials.
Wilson, who has maintained a "hold" on MedImmune,said he will not change that rating until results of thestudies are disclosed.
"MedImmune said the Prevent trial was statisticallysignificant," Wilson said. "But how good does that datalook?"
MedImmune officials expect Baxter Healthcare Corp., ofDeerfield, Ill., to be more enthusiastic. Thepharmaceutical company last month took a chance onRespigam, licensing rights to sell the drug outside theU.S. The deal included an $9.5 million equity investmentin MedImmune plus the possibility of another $20 millionbased on specific sales milestones. If the Phase III trialsfailed, Baxter was to receive additional MedImmuneshares at no cost.
MedImmune has a partnership with American HomeProducts Corp., of Madison, N.J., for marketingRespigam in the U.S.
The Prevent trial targeted prematurely born infants andthose with a lung disease called bronchopulmonarydysplasia. The study, at 54 medical centers, began inNovember 1994 and ended in May. The Cardiac trial,which was started in 1992 and completed in May, testedthe drug at 34 medical centers in another patient group athigh risk for RSV _ children with congenital heartdisease.
Both studies were blinded and the Respigam dosage, 750mg/kg, was the same. In the Prevent trial the drug wascompared with placebo and in the Cardiac study thecontrol group received either placebo or no drug.
No Deaths Attributable To Respigam
With RSV treatments, Mott said, "you don't eliminate theinfection, you reduce the severity." Mott also noted thatalthough patient fatalities occurred during the trials, thedeaths resulted from the children's primary illnesses, suchas lung and heart diseases and complications associatedwith premature birth. The company said no deaths wereattributed to Respigam.
Of the 32 fatalities in the two trials, 18 children diedamong those treated with the drug and 15 patients died inthe control or placebo groups.
"We've now conducted studies on 1,250 children andmade 25,000 infusions of the drug," Mott said. "We havea very significant data base to submit to the FDA formarketing approval."
Respigam, designed as a preventive therapy, is derivedfrom RSV antibodies extracted and purified from humanblood plasma. The only FDA approved treatment forRSV is the antiviral agent, ribavirin, or Virazole, which ismade by ICN Pharmaceuticals, of Costa Mesa, Calif.
Mott said more than 300,000 infants born each year in theU.S. are at high risk of developing severe RSV becausethey were premature or suffer from heart and lungdiseases. While most children become infected with RSVduring their first three years, the virus normally is notserious in healthy youngsters.
For those high risk infants who develop the disease,91,000 are hospitalized each year and 4,500 die.
MedImmune has two other drugs on the market.CytoGam is a polyclonal antibody for the prevention ofcytomegalovirus in kidney transplant patients and Zosynis an anti-infectant. n
-- Charles Craig
(c) 1997 American Health Consultants. All rights reserved.