FDA Panel Backs Agent for ALL Subtype

Nick Mulcahy

March 22, 2012

March 22, 2012 — The US Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee (ODAC) voted yesterday to support a New Drug Application for vincristine sulfate liposomes injection (VSLI; Marqibo, Talon Therapeutics) for the treatment of adult patients with Philadelphia chromosome negative acute lymphoblastic leukemia (ALL) in second or greater relapse or whose disease has progressed after 2 or more treatment lines of antileukemia therapy.

The vote was not won, however, by a large majority; 7 members voted yes, 4 voted no, and 2 abstained.

According to an FDA briefing document, VSLI has been developed to increase the tolerable dose of the active moiety, vincristine, while reducing its dose-limiting neurotoxicity.

"We are very pleased the majority of the ODAC members agree that [VSLI] offers a meaningful benefit/risk ratio for a very rare patient population that has a grave prognosis and no current standard of treatment," said Steven Deitcher, MD, president and chief executive officer of Talon Therapeutics, in a press statement. "Based on prior FDA discussions, we have received Special Protocol Assessment agreement for a large randomized phase 3 trial in front-line adult elderly ALL with sites currently open for enrolment."

As of February 2012, this confirmatory trial, which will compare standard vincristine with VSLI, had not enrolled any patients, the FDA noted.

The submission is based on the results of a phase 2 single-group study, supported by a phase 1/2 single-group dose-finding study.

The primary efficacy end point in the phase 2 study was the proportion of patients who achieved a complete response (CR) or a complete response with incomplete blood count recovery (CR+CRi). The rate of CR+Cri was 15.4% (10 of 65), with 3 CRs and 7 CRis.

In the studies, neuropathy-associated adverse events during the VSLI treatment period were reported by 72 of 83 patients (86.7%) who received 2.25 mg/m² of VSLI, and grade 3 neuropathy adverse events were reported by 27 (32.5%). Overall, 96.4% of patients who received 2.25 mg/m² of VSLI reported grade 3 adverse events, and 75.9% reported any serious adverse event. In the phase 2 study, 15 patients (23.1%) died during the treatment period.

The ODAC provides the FDA with independent expert advice and recommendations; however, the final decision regarding approval is made by the FDA.

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