[Updated: 10:05 am Eastern, 3/22/10] The chief of cancer drug reviews at the FDA, Richard Pazdur, laid out a harsh critique this morning of a new drug that Cell Therapeutics is hoping will win approval for the U.S. market.
The company’s case for pixantrone (Pixuvri) is being heard this morning in front of the Oncologic Drugs Advisory Committee meeting at a hotel in Gaithersburg, MD. Cell Therapeutics (NASDAQ: [[ticker:CTIC]]) is seeking approval for pixantrone to treat a very sick group of patients with relapsed forms of non-Hodgkin’s lymphoma that have already gotten two prior rounds of therapy.
The panel’s recommendation to the FDA is vital for Cell Therapeutics. The company has no marketed products, and pixantrone represents its only chance of a candidate that could generate U.S. sales anytime soon. Cell Therapeutics had $37.8 million in cash and investments heading into this year, which isn’t enough on its own to operate the business through the end of September. If pixantrone is approved, Cell Therapeutics officials estimate the company can start tapping into a market of about 10,000 U.S. patients each year.
The Cell Therapeutics application hinges on a 140-patient study, known as Extend or PIX301. This study randomly assigned patients to get pixantrone or the physician’s choice of another chemotherapy drug. The study’s main goal was to show the treatment could completely wipe out tumors. About 20 percent of patients on pixantrone (14 out of 70) had a “complete response” compared with 5.7 percent (4 out of 70) who did that well in the control group.
“We believe pixantrone produced a favorable benefit to risk profile,” for patients with no other options, said CEO James Bianco.
But Pazdur made it clear that the company’s application falls short of what the FDA usually wants in an application.
Pazdur started his talk this morning by pointing out that the Cell Therapeutics application depends on a “single incomplete trial.” That’s because PIX301/Extend was supposed to enroll 320 patients over 36 months, but was halted after 45 months went by, and only 140 patients had enrolled.
Since the company was unable to enroll the full number of patients, it needs a higher than usual degree of statistical confidence than usual to ensure the findings weren’t a fluke, Pazdur said. The statistical threshold that studies usually aim for is “p-value” of 0.05, which means there’s only a five percent chance of a finding being the result of chance. Since the Cell Therapeutics study only enrolled 44 percent of the planned patients, the p-value should be adjusted to 0.0096, meaning there’s less than a 1 percent chance of the results being due to chance, Pazdur said. On that higher bar, this Cell Therapeutics trial fell short of its threshold, Pazdur noted. The p-value of the Extend study was 0.021.
Since the study failed to reach this statistical standard for convincing proof on the its main goal, that also means that secondary goals of the study—like whether it helped patients live longer—also fall short, Pazdur said.
And Pazdur had more objections. He noted that only eight of the 140 patients enrolled at sites in the U.S., even though the company had arranged for 28 U.S. sites to enroll patients. The enrollment was poor because many patients opted for other combination treatments, simple pain relief at the end of life, or a competing drug, rituximab (Rituxan), Pazdur said. The lack of U.S. patients means there’s a question of whether the results are generalizable to a patient population in the U.S., Pazdur said. It’s important to have patients in the U.S. in the study, because they tend to get more pre-treatments, which can affect their prognosis, the FDA said.
Bianco, during the company’s presentation, said the company tried its best to speed up enrollment. It increased the number of clinical sites, hired regional firms to recruit patients, and did Web-based outreach to clinical trial investigators. “Accrual was difficult and slow,” Bianco said.
[Updated: 10:05 am Eastern] Plus, remember those 14 patients out of 70 who had their tumors completely wiped out after getting pixantrone? The FDA, in its staff presentation, said that upon further review of their tumors, 5 of those 14 responders actually had slow-growing tumors—not the fast-growing, aggressive tumors that all patients were supposed to have in the study.
Then there were some noticeable side effects which Pazdur pointed out. About 9 percent of patients quit taking the Cell Therapeutics drug after they had white blood cell depletion, while no patients in the control group quit taking their treatment for that reason, Pazdur said. Patients also had severe heart toxicity in the trial, Pazdur said.
While the FDA usually follows the advice of its panels, it isn’t required to do so. The panel is scheduled to make its recommendation by Noon Eastern time today. The FDA’s deadline to make a decision on the pixantrone application is April 23.
