BETHESDA, Md-Troubled by the small size of the studies presented to it, the FDA’s Oncologic Drugs Advisory Committee (ODAC) declined to vote on whether to make a recommendation regarding DepoCyt (cytarabine lipid-particle injection, DepoTech Corp.).
BETHESDA, MdTroubled by the small size of the studies presented to it, the FDAs Oncologic Drugs Advisory Committee (ODAC) declined to vote on whether to make a recommendation regarding DepoCyt (cytarabine lipid-particle injection, DepoTech Corp.).
The company had sought approval for the drug for the intrathecal treatment of neoplastic meningitis in patients with solid tumors.
The decision, however, does not in any way indicate how ODAC might view the drugs use in lymphoma or leukemia patients who develop neoplastic meningitis, also called carcinomatous meningitis, said committee chair Janice Dutcher, MD, professor of medicine, Montefiore Medical Center, the Bronx. Studies of DepoCyt in such patients are currently in progress.
While we are clearly disappointed with todays outcome, we believe in the value of this product, Edward L. Erickson, DepoTechs president and chief executive officer said after the ODAC meeting. We recognize it is important that we work closely with the FDA to define a path forward.
DepoCyt is an injectable, sustained-release formulation of the anticancer agent cytarabine. It is encapsulated in microscopic, spherical lipid particles and delivered in suspension. The drug is released slowly as the spheres walls erode or reorganize. The drug was developed jointly with Chiron Corp.
DepoTech presented three studies to support its new drug application: a phase III trial of 61 patients (31 treated with DepoCyt; 30 with methotrexate), a 4-patient pharmacokinetic study, and a phase I trial involving 11 patients. The difficulty in interpreting the data is the small numbers, said FDA reviewer Steven Hirshfield, MD.
He also acknowledged the difficulty of assessing drug efficacy in this disease, since patients often die of their primary cancer, and cause of death may be difficult to assess.
The Committee Vote
ODAC members decided against a recommendation vote after addressing three questioned posed by the FDA staff. The panel voted 7 to 3, with one abstention, that the three studies that produced the data could not be considered adequate and well controlled.
It split 5 to 5, with one abstention, in answering the question: In patients with carcinomatous meningitis from solid tumors, is the cytological response of the CSF sample in the absence of clinical progression a surrogate endpoint that predicts clinical benefit.?
Finally, the committee voted 10 to 0, again with one abstention, that the trials failed to show substantial evidence of the efficacy of DepoCyt.
The pivotal study of the agent in neoplastic meningitis from solid tumors was one arm of a three-tined investigation of DepoCyts effectiveness against neoplastic meningitis. A study of DepoCyt in lymphoma patients with neoplastic meningitis will be completed later in 1998, and one testing the drug in neoplastic meningitis of leukemia is ongoing.
In addition, DepoTech is continuing its investigation of DepoCyts effectiveness against neoplastic meningitis in patients with solid tumors in phase IV studies in the US and Canada. The company has also filed a marketing authorization application in Europe for the product.
Mr. Erickson said that DepoTech intends to review with the FDA the totality of information we have on the product, including data from randomized trials in lymphoma and leukemia and information from the ongoing trials of DepoCyt in solid tumor patients. w