ODAC Says DaunoXome Should Be Approved for HIV-Associated KS

ROCKVILLE, Md--The FDA's Oncologic Drugs Advisory Committee (ODAC)has unanimously recommended approval of DaunoXome (liposomal daunorubicin)as first-line therapy for the treatment of advanced HIV-relatedKaposi's sarcoma (KS). The usual treatment, a combination of Adriamycin,bleomycin, and vincristine (ABV), is not well tolerated over thelong haul, especially when given with antiretroviral agents (ddI,ddC, and AZT).

DaunoXome was developed by Vestar, Inc., which has since mergedwith NeXagen, Inc. to form NeXstar Pharmaceuticals, Inc., Boulder,Colorado.

In a prospective, randomized phase III clinical trial of 227 patientswith advanced KS who had not received prior systemic chemotherapy,half the subjects were given DaunoXome, 40 mg/m² every 2weeks, and the other half received ABV.

Average survival for the DaunoXome group was 12 months, whichis at least comparable to ABV, said principal investigator ParkashS. Gill, MD, of the University of Southern California, and MichaelE. Ross, MD, NeXstar's vice president for clinical and regulatoryaffairs.

Time to progression of disease was better with DaunoXome thanwith ABV, and time to treatment failure and overall response ratewere the same for both the DaunoXome and ABV groups.

DaunoXome had fewer adverse effects than ABV, the company said.The alopecia, neuropathy, and fatigue seen with use of DaunoXomewere all substantially less severe than the adverse effects ofABV. Subjects taking DaunoXome had less need for premedication,and they showed no excessive renal or hepatic dysfunction.

The company said that DaunoXome patients maintained their weightgain and maintained an acceptable quality of life for a longertime than did patients who received ABV therapy.

FDA analysis of the NeXstar data showed that DaunoXome does indeedhave a biological effect on HIV-related KS, although the responserate in the randomized trial was less than anticipated for bothDaunoXome and ABV, probably due to the strict criteria used tomeasure response in this study. The ODAC members agreed that DaunoXomeis comparable to ABV in terms of effectiveness and safety as first-linetherapy.