FDA Approves Marqibo for Rare Form of Leukemia

The FDA approved vincristine sulfate liposome injection (Marqibo; Talon Therapeutics) to treat patients with Philadelphia chromosome-negative (Ph-) adult acute lymphoblastic leukemia (ALL) following at least two relapses or failed treatment with at least two anti-leukemia medications.

Vincristine sulfate is an anti-mitotic drug, or one that inhibits cell division in tumors and thus slows the progression of tumor growth. When encapsulated in liposomes, the drug can be delivered in a targeted fashion in high concentrations. Vincristine sulfate is an anti-cancer agent that is already available, but the dosage recommendations are different for Marqibo.

The once-weekly injectable treatment is the first drug manufactured by Talon Therapeutics to be approved for any oncologic indication.

“We are delighted that Marqibo will be available to a patient population with an underserved hematologic malignancy,” said Steven R. Deitcher, MD, President, Chief Executive Officer, and Board Member of Talon Therapeutics, in a statement released on Thursday. “This represents a transformational event for Talon and fulfillment of our most important corporate goal, to date.”

ALL is relatively rare in adults, with about 2,000 new cases diagnosed annually in the United States. Of those, about 1,400 are Ph- adult ALL cases. In the United States each year, approximately 840 patients with Ph- adult ALL relapse from remission or are refractory to front-line therapy. The median survival of patients with second or greater relapsed and refractory ALL is below 3 months.

In March, the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 7-4 with two abstentions in favor of recommending the drug for approval. The FDA originally set the action date for the drug in May. However, early that month, the FDA asked Talon Therapeutics for information about the drug that wasn’t related to clinical trials, and announced it would add 3 months to its timetable for considering the treatment’s approval.

The decision by the FDA was primarily based on the results of the phase II HBS407 trial. In the international, multicenter, open-label, single-arm trial, 65 adult patients with Ph- ALL who had at least two relapses or prior treatment with at least two other leukemia medications received Marqibo.

An initial assessment performed by the researchers found that complete remission (CR) or complete remission with incomplete blood count recovery (CRi) was achieved in 13 patients, though an independent analysis by the FDA found that only 10 patients had achieved CR or CRi, with a median duration of response of 28 days. The FDA also reported that the median time to the first event of relapse, death, or next therapy for those patients was 56 days.

Toxicity has been an issue for patients in clinical trials of the drug, all of whom reported experiencing adverse events (AEs); according to investigators, 81.5% of the patients in the HBS407 study experienced at least one AE that was related to treatment. In that study, grade 3 or higher AEs were reported in 95.4% of patients, with 61.5% of those events attributed, by investigators, to the treatment. In HBS407 and a smaller Marqibo study called VSLI-06, the most frequently reported AEs were constipation (57.4%), nausea (51.5%), pyrexia (42.6%), and fatigue (40.6%).

In HBS407, 15 patients died during the treatment period and 45 additional patients died during the follow-up period. ALL was responsible for 64.6% of the fatalities. Complications related to hematopoietic stem cell transplantation, brain infarction, intracerebral hemorrhage, liver failure, and sudden cardiac death also resulted in death; in some cases, these events were attributed to complications of ALL disease progression.

Richard Pazdur, MD

Despite these concerns, the FDA granted the drug an accelerated approval, meaning that the drug is likely to produce positive results in patients with a serious disorder. The drug was also granted orphan-product designation because it’s designed to treat a relatively rare condition.

“Marqibo’s approval demonstrates the FDA’s commitment to the development and approval of drugs that address serious, unmet medical needs,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Marqibo provides an additional option for Philadelphia chromosome negative acute lymphoblastic leukemia patients whose disease is unresponsive to available therapies.”

Marqibo will carry a Boxed Warning stating that the drug is only to be given intravenously because of a high risk of death associated with the drug if administered in other ways.

A phase III study designed to evaluate the efficacy of Marqibo in ALL patients who are at least 60 years old is currently recruiting patients.