Although members of the FDA's Oncologic Drugs Advisory Committee (ODAC) were admittedly underwhelmed Wednesday by the data for Talon Therapeutics Inc.'s Marqibo, they voted 7 to 4, with two abstentions, that the drug demonstrated a favorable risk-benefit profile as a third-line treatment for adults with Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL).

Even some members who voted for the drug didn't give it a ringing endorsement.

Committee Chairman Wyndham Wilson, chief of the lymphoma therapeutics section at the National Cancer Institute, said his vote was more a reflection of the lack of other therapies.

Generally, he said, single-arm trials used to support accelerated approval need much more robust response data than the 15 percent response noted in the Marqibo (vincristine sulfate liposomes injection) Phase II trial that enrolled 68 patients.

Wilson noted that, in the past, ODAC has said a randomized trial is preferred for accelerated approval. Absent that, a trial needs to produce "very compelling" response data.

"Here, we're skirting along the bottom with these response rates," he said. But given that Marqibo did produce a response and there are no other approved therapies for that specific indication, he decided to give Talon's drug the benefit of the doubt.

Some of the other members who voted yes were more positive in their support of the drug, which is a new version of vincristine, a long-used cancer standard, that can be administered on an outpatient basis. That fact, along with the potential to facilitate stem cell transplants and fewer toxicities than other therapies, was cited as reason enough to support the drug.

The vote boosted the stock price of the San Mateo, Calif.-based company (OTCQB:TLON) more than 20 percent Wednesday afternoon, though it dropped back to close at 82 cents, up 8 cents. But it at least regained some of what it had lost Monday when the FDA released the briefing documents ahead of the committee meeting. (See BioWorld Today, March 20, 2012.)

If approved, Marqibo would be used in a small patient population of about 500 adults per year. But Talon has an extensive development program for the drug in other oncology settings, including a large, randomized Phase III trial as front-line treatment in elderly patients with ALL. The company has proposed using that active trial, which is expected to enroll about 400 patients globally under a special protocol assessment, as its confirmatory trial for accelerated approval.

The design of that trial had some panel members questioning whether it is doable. In fact, Ralph Freedman, a professor at the University of Texas M.D. Anderson Cancer center, said he was leaning toward voting for the drug, but his concerns about the feasibility of the confirmatory trial led him to abstain.

Brent Logan, a biostatistics professor at the Medical College of Wisconsin, cited his concerns about the trial as one of the reasons for his negative vote. The trial is a head-to-head study comparing Marqibo with standard vincristine in multiple-agent therapy.

Given the 60-plus age group of the trial, Logan questioned the feasibility of accrual. The toxicities of standard vincristine and other drugs used in the multiple-agent therapies tend to worsen with age.

One of the most supportive of the drug, Mikkael Sekeres, an associate professor and staff member at the Cleveland Clinic Taussig Cancer Institute, encouraged the FDA, if it granted accelerated approval, to hold Talon's feet to the fire to ensure the confirmatory trial is done robustly and in a timely manner.

Several other panel members echoed that sentiment, adding that the agency should yank the approval if Marqibo doesn't measure up in the confirmatory trial.

They noted that some sponsors of other cancer drugs granted accelerated approval have dropped the ball on their post-approval studies, which means the drugs are not fully approved and can't be considered standard of care.

Following the vote, Talon President and CEO Steven Deitcher said in a press release that the company will work with the FDA to address remaining questions prior to Marqibo's May 13 PDUFA date.

Despite the lack of overwhelming support, Wednesday's ODAC vote was a turnaround from the first time Marqibo went before the committee, seeking a thumbs-up for accelerated approval in non-Hodgkin's lymphoma. That time, ODAC said a randomized trial would be needed for approval.

A few months later, the FDA followed up with a not-approvable letter. (See BioWorld Today, Dec. 2, 2004, and Jan. 20, 2005.)