The FDA’s Oncologic Drug Advisory Committee (ODAC) voted 7-4 (2 abstentions) in support of vincristine sulfate liposomes injection (Marqibo; Talon Pharmaceuticals) to treat patients with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) following at least two relapses or failed treatment with at least two anti-leukemia medications. The FDA is scheduled to make its final approval decision by August 12, 2012.
“We are very pleased the majority of the ODAC members agree that Marqibo 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 R. Deitcher, MD, president, chief executive officer, Talon Therapeutics, in a statement released after the panel’s vote.
ODAC made its determination that the benefits associated with Marqibo outweighed its risks based on data from the phase II HBS407 trial. The international, multicenter, open-label, single-arm trial assessed the effectiveness of Marqibo in 65 patients with Ph- ALL who had least 2 relapses or prior treatment with at least 2 other leukemia medications.
In the researcher’s initial assessment, 13 patients achieved either complete remission (CR) or complete remission with incomplete blood count recovery (CRi). However, the FDA’s assessment found that 10 patients had achieved CR or CRi. The FDA also determined the median duration of CR and CRi was 28 days.
In both HBS407 and a previous, smaller Marqibo study (VSLI-06), all patients reported adverse events (AEs). In HBS407 specifically, 95.4% of patients reported AEs of grade 3 or higher. Between both trials, the most frequently reported AEs were constipation (57.4%), nausea (51.5%), pyrexia (42.6%), and fatigue (40.6%).
Fifteen patients died during the HBS407 treatment period, and 45 patients died during the follow-up period. Most of the fatalities (64.6%) were caused by ALL, but other deaths were attributed to complications of hematopoietic stem cell transplantation, brain infarct, intracerebral hemorrhage, liver failure, and sudden cardiac death.
Despite Marqibo’s toxicity profile, the majority of the FDA panel recommended approving the drug.
A proposed phase III confirmatory study for patients aged 60 years or older with newly diagnosed ALL is currently enrolling patients.