[[Updated: March 16, 5:50 pm. Adds comments from chief medical officer Jack Singer and clarifies study results.]] Cell Therapeutics is betting its future on winning FDA approval of a drug that looks effective for non-Hodgkin’s lymphoma, but now comes word that patients on the drug in a clinical trial had a higher number of heart problems than those in a control group.
The Seattle-based biotech (NASDAQ: [[ticker:CTIC]]) disclosed that important fact today on page 7 of its annual report filed with the Securities and Exchange Commission. The finding comes from a study of 140 patients, called Extend, that randomly assigned patients to get an experimental drug, pixantrone, or another chemotherapy drug. The study found pixantrone was effective at completely shrinking tumors for 20 percent of patients, compared with 5.7 percent in a control group, according to a company statement we reported on in November. But the effectiveness apparently came with a side effect. Five of the patients in the pixantrone group had “severe cardiac events,” compared with two in the control group, the company said today in the annual report.
Cell Therapeutics acquired pixantrone for $236 million back in June 2003, when it acquired Italy-based Novuspharma. The drug is a modified version of an anthracycline, and is supposed to be designed to be less toxic to the heart than other drugs in its class. Cell Therapeutics, which has been scrambling to cut costs and raise capital in a last-ditch bid to stay in business, says its strategy is to submit the results of the pixantrone trial in the first half of this year to the FDA. If the FDA decides to give this application an expedited six-month review, Cell Therapeutics could find out before the end of 2009 whether the drug is good enough to win approval. Yet the company says even after selling off its lone marketed drug, Zevalin, and cutting 28 percent of its domestic workforce, it still doesn’t have enough operating cash to run past May.
The higher incidence of heart problems shouldn’t harm Cell Therapeutics’ application to the FDA, says company spokesman Dan Eramian. The finding from the Extend study doesn’t demonstrate that the drug caused the heart problems, which could have been caused by other things, says Jack Singer, the company’s chief medical officer.
“The numbers are too small to be statistically significant,” Eramian says, meaning the side effect could have been due to chance, rather than the drug.
Pixantrone has been studied in more than 400 patients overall, many of whom had prior treatments that are toxic to the heart, and the drug’s “safety profile is about as good as one could hope for,” says Jack Singer, Cell Therapeutics’ chief medical officer, in an interview. He says the full results of the Extend study will be presented at the American Society of Clinical Oncology’s annual meeting, scheduled for late May and early June.
The heart problem appears to be the most serious, but it wasn’t the only side effect seen in the trial with pixantrone. The study found that patients on pixantrone had a higher risk of leucopenia and neutropenia, common side effects from chemotherapy drugs in which white blood cells get depleted and can make patients vulnerable to infections. Researchers, however, found few cases of severe neutropenia, vomiting, or diarrhea, the company said. “Overall, the incidence of serious side effects was similar between pixantrone and the control arm,” the company said.
Swiss drug giant Novartis has an option to enter into an exclusive worldwide license to develop and commercialize pixantrone, although it hasn’t yet chosen to exercise that option, Cell Therapeutics says. If Novartis exercises that option, Cell Therapeutics would get $7.5 million in a license fee, as much as $104 million in registration and sales related milestones, and a royalty on worldwide sales.
If Cell Therapeutics can get that $7.5 million milestone fee, that would represent about 3.5 months of operating cash, since its monthly cash spending rate has been cut down to about $2.1 million. The company cut 34 jobs, or about 28 percent of its workforce earlier this month, bringing its total staff down to about 88 employees. Cell Therapeutics also said last month it is closing its Italian branch, eliminating 62 jobs there.
