DepoTech Corp. and Chiron Corp. said Wednesday thatinterim results from a Phase III trial of DepoCyt show thesustained-release product is achieving statisticallysignificant results in the treatment of neoplasticmeningitis arising from solid tumors.
Neoplastic meningitis occurs when metastases from solidtumors, leukemia or lymphoma spread to the tissuesurrounding the brain or spinal cord. The spread fromsolid tumors accounts for about 80 percent of the cases.
DepoCyt is an injectable formulation of thechemotherapeutic agent cytarabine (ara-C) encapsulatedin DepoFoam, a lipid-based delivery technology. Chiron,of Emeryville, Calif., made a $2.5 million equityinvestment in privately held DepoTech in April 1994 aspart of a collaboration on the DepoCyt.
The data released Wednesday include analyses from 32patients in the 40-patient solid-tumor arm of the trial.Two other arms _ involving disease arising fromlymphomas and leukemia _ also will have about 40patients in each. Patients in the solid-tumor arm weretreated with either DepoCyt or methotrexate, the currentstandard therapy.
The response rate for the 15 DepoCyt-treated patients was47 percent compared to 6 percent for the 17 patientstreated with methotrexate. Median survival in theDepoCyt group was 277 days vs. 68 days in themethotrexate group.
The companies, after seeing the interim data, amendedthe trial protocol to allow patients who failed to respondto one treatment to be switched over to the other.Response was defined as two consecutive negativecytologies of cerebral spinal fluid.
Edward Erickson, president and CEO of La Jolla, Calif.-based DepoTech, said the FDA will allow the filing of anew drug application once studies of any of the threesubtypes are completed, rather than waiting for all 120patients to complete therapy. The solid-tumor arm, whichwas easiest to enroll, is expected to be completed by theend of the year. About eight patients with small-cell lungcancer and breast cancer still need to be accrued.
Erickson said the leukemia and lymphoma parts of thetrial are under way.
DepoFoam is composed of small particles containinghundreds of internal chambers, much like the spaces in asponge. The water-filled chambers are separated by asingle bilayer lipid membrane. Water-soluble drugs maybe dissolved in the chambers for sustained release wheninjected into the body.
The "injectable tiny time capsules," Erickson said, can bedelivered via subcutaneous, intrathecal or intramuscularinjection to get them to the tumor area. There is nospecific targeting mechanism.
Chiron has exclusive marketing rights to the product inCanada, the U.S. and Europe. DepoTech hasmanufacturing rights. There also are milestone and cost-sharing provisions, Erickson said, and an undisclosedprofit-split formula.
As part of the original agreement, Chiron gained anoption to market three additional sustained releasechemotherapeutics being developed by DepoTech. Andthe companies are working on DepoFoam formulations ofChiron's interleukin-2 and insulin-like growth factor-1products.
DepoTech has preclinical work under way with anantibacterial product called DTC 201, a DepoFoamformulation of amikacin. Erickson said an investigationalnew drug application is forthcoming for that drug. Furtherbehind, the company is working on a morphine product.DepoTech has an early stage collaboration with Merck &Co. Inc., of Whitehouse Station, N.J., in the area ofvaccines. n
-- Jim Shrine
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