BERLEX LABS' FLUDARA APPROVED APRIL 18

Executive Summary

BERLEX LABS' FLUDARA APPROVED APRIL 18 for the treatment of patients with B-cell chronic lymphocytic leukemia. The injectable drug is indicated for patients who have not responded to other treatments or whose disease has progressed during treatment with at least one standard alkylating agent-containing regimen. The approval for Fludara (fludarabine) comes approximately 17 months after the NDA was filed on Nov. 22, 1989. Fludara, an orphan drug, has been available to patients with refractory chronic lymphocytic leukemia since November 1989 through a Group C/Treatment IND. FDA's Oncologic Drugs Advisory Committee unanimously recommended Fludara for approval at its Sept. 11, 1990 meeting ("The Pink Sheet" Sept. 17, p. 3). Chronic lymphocytic leukemia is diagnosed in about 9,600 U.S. patients each year. For some time Fludara has been rated by FDA as a "1A" drug, a new chemical entity representing an important therapeutic gain over existing therapies. In one of the studies presented at the advisory committee meeting, the South West Oncology Group's Phase I/II study, patients received 15-25 mg/m bolus infusions of fludarabine over 30 minutes for five days every four weeks. Among the 32 patients in the SWOG study, four (13%) had complete responses and six (19%) had partial responses. In another study, the M. D. Anderson Phase I/II trial, patients were given 22-40 mg/m bolus infusions over 30 minutes for five days every three to four weeks. Of the 101 patients enrolled in the study, six (13%) evaluable patients had complete responses, and 17 (35%) had a partial response to treatment with Fludara. The median duration of response was 65 weeks in the SWOG study and 91 weeks in the Anderson trial, with median survival ranging from 82 to 137 weeks. During the meeting, an investigator noted that refractory CLL patients usually have an expected response rate of 5% to 10% and a median survival of six to 12 months. The committee based its recommendation mostly on response rates rather than survival data, given the lack of appropriate historical controls. Berlex' German parent, Schering AG, acquired Fludara when it purchased the pharmaceutical R&D operations of Triton Biosciences from Shell Oil ("The Pink Sheet" Sept. 24, 1990, T&G-2). That deal was announced nine days after the drug received the advisory committee's approval recommendation. Fludara was licensed from the National Cancer Institute in 1984.