WASHINGTON _ The FDA's Oncology Drugs AdvisoryCommittee (ODAC) on Thursday recommended approval ofDaunoXome, NeXstar Pharmaceuticals Inc.'s liposomal formation ofthe anticancer agent daunorubicin, as the first-line therapy fortreatment of advanced Kaposi's sarcoma.
NeXstar asked NASDAQ to suspend trading on its stock lateWednesday until ODAC made its recommendation. On Thursday, theBoulder, Colo. company's stock (NASDAQ: NXTR) jumped 29percent on the news, closing at $9.25 per share.
Eight of the committee members voted in favor of recommendingapproval but one member abstained. George Omura, a University ofAlabama medical professor, withheld his endorsement because ofconcern that DaunoXome may make patients susceptible toopportunistic infections at a much higher rate than standardchemotherapy. Omura said he wanted a comparison betweenDaunoXome and its non-liposome packaged form of adriamycinbefore he would feel comfortable with the data NeXstar presented.
ODAC Chairman Charles Schiffer, University of Maryland CancerCenter, categorized ODAC's approval of DaunoXome as a precedent.Referring to NeXstar's randomized Phase III clinical trial which waspraised several times by the committee, Schiffer said, "the playingfield has been changed. The next agent will have to address the factthat a randomized clinical trial can be performed."
"The next drug manufacturer seeking approval before FDA will findit more difficult to prove its case," Schiffer said.
"By performing a randomized clinical trial, NeXstar clearly put itselfat a competitive advantage over Liposome Technology Inc [of MenloPark, Calif.] which completed only a Phase II clinical trial andreceived approval for its liposomal agent Doxil-SL as a second linetherapy for Kaposi's sarcoma patients who have failed othertherapies," said Rob Faulkner, an S. G. Warburg analyst in NewYork.
"By giving FDA a randomized controlled trial, NeXstar achievedfirst line therapy designation for its drug, giving it an advantage in amarket for two liposomal products that are similar," Faulkner toldBioWorld Today.
Faulkner said the next question to be answered is whether the FDAwill approve both drugs and if its does, how it would defineindications in the labeling.
"ODAC's approval exorcises the ghost of two years ago," saidNeXstar spokesman Joe Alper. He referred to ODAC's rejection ofDaunoXome two years ago based on a critical review of an equivocalPhase II study. (See BioWorld Today, June 18, 1993, p. 1.)
"Not only is this great for our company but it's great for the biotechindustry which hasn't seen too many Phase III drugs approved,"Alper said.
Alper offered praise for the FDA which "in recent weeks has been farmore open. NeXstar has had a useful dialog with FDA to discusstheir questions about our data. We understand that FDA's vigilance isthe price we pay for quality pharmaceuticals," said Alper.
The advisory panel action comes two days after NeXstar announcedthat the Swedish Medical Product Agency had approved DaunoXomefor Kaposi's sarcoma. (See BioWorld Today, June 7, 1995, p. 3.)
While the committee was comfortable with the efficacy datacompiled by NeXstar, its primary concern was the toxicity ofDaunoXome. "The safety profile is different but similar forDaunoXome and ABV [the standard chemotherapy regimen ofadriamycin, bleomycin and vincristine]," noted panel member PaulBunn, director of the University of Colorado Cancer Center.
"While ABV is associated with increased neuropathy, DaunoXome ismore myelosuppressive," Bunn said. "If I were a clinician I mightchoose ABV. But DaunoXome's safety profile is OK for approval _it's no better and not worse than ABV."
"More problematic is whether the liposomal product formulation isassociated with long term cardiotoxicity," said panel member JudithOchs, a consultant with Tomorrows Children's Institute, Hackensack,N.J. "The data suggests that cardiotoxicity is less with the liposomalformulation."
ODAC unanimously rejected permitting the manufacturer to includein the labeling a statement that a higher dose of 60mg/m2 was safe inpatients who had failed on the 40mg/m2 DaunoXome therapy andchemotherapies.
"The labeling should make it clear that there is considerable toxicityassociated with the higher dose and the response rate is not higher,"Bunn said.
FDA Reviewer Robert White had a different take on NeXstar's data.White was concerned that its quality of life data were not asoptimistic as the company maintained. NeXstar reported fewer sideeffects with DaunoXome such as reduction in nausea, a drop inweight and hair loss.
In addition, White questioned whether there was a clinicalsignificance associated with DaunoXome and a higher rate ofopportunistic infections than reported with standard chemotherapies.He also questioned whether long-term survival with DaunoXometherapy was as good as other standard treatments. n
-- Michele L. Robinson Washington Editor
(c) 1997 American Health Consultants. All rights reserved.