By Randall Osborne
Cell Therapeutics Inc. (CTI) reported negative preliminary results from a Phase III trial of lisofylline for bone marrow transplant patients, but the bad-news data came "by the luck of the draw" and may be overcome by a larger study picture, the company's CEO said Wednesday.
The trial failed to meet its primary endpoints — reductions in neutropenia-related infections and in mortality associated with treatment for bone marrow transplant — because four of 17 centers used high radiation and chemotherapy despite the higher-risk profile of patients, whose median age was 46 years, said James Bianco, CTI's president and CEO.
"It's like having a race between an 80-year-old and a 20-year-old, and they tie," he added. "Do you say the 80-year-old lost?"
The subtleties were lost on Wall Street. CTI's stock (NASDAQ:CTIC) ended Wednesday at $4.43, a 53 percent drop from Tuesday's close of $9.50.
"By the luck of the draw, the majority of those intensive [radiation and chemotherapy] regimens ended up in the treatment arm," he said.
Seattle-based CTI's earlier Phase II trial of lisofylline, an anti-inflammatory small molecule, reserved the intensive regimens for younger patients with relapsed disease, Bianco added.
"My impression is that the clinicians had positive experience with this product in the past — patients did extremely well, even with intensive regimens — so they let those practices continue," he said.
The Phase III trial is designed to test the safety and efficacy of lisofylline in patients with hematological malignancies who are undergoing bone marrow transplants from HLA-identical sibling donors. HLA stands for human leukocyte antigen.
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Even with the intense treatment regimen, overall mortality was lower than expected for the high-risk group in the study, and subset analyses are consistent with the Phase II trial, showing a positive effect on mortality, Bianco said.
"Our subset analysis made the high-risk group look like a low-risk placebo group," he added. "This particular trial taught that, in a high-risk population, the drug may confer some benefit."
Bianco said the trial will be "supportive of an integrative package" of data in filing a new drug application with the FDA, which probably will happen in the second quarter of next year rather than by the end of this year, as the company had planned.
In another ongoing Phase III trial — for bone marrow transplant patients with unrelated donors — the treatment regimen is more standardized, and the company does not expect to run into similar problems.
Carolyn Paradise, CTI's head of medical affairs, said the unrelated-donor trial is slated to "go past the end of the year, but not much." Another Phase III trial is ongoing in patients with acute myeloid leukemia.
"Right now, they're looking like they are scheduled to complete at about the same time," Paradise said.
Lisofylline is partnered for oncology indications with Johnson & Johnson (J&J), of New Brunswick, N.J. Last month, the National Institutes of Health backed CTI's pivotal trial of the drug for acute lung injury, the precursor to acute respiratory distress syndrome. J&J has an option to license lisofylline for that indication as well. (See BioWorld Today, Feb.23, 1998, p. 1.) *