By Jim Shrine
A Phase III trial of lisofylline by Cell Therapeutics Inc. (CTI) ended up producing some positive news for the company, nine months after the compound failed to meet is primary endpoints in a pivotal study in bone-marrow transplant patients.
Lisofylline showed a statistically significant benefit in preventing graft vs. host disease (GVHD), following bone-marrow transplantation from HLA-identical donors. Those results were presented for the first time at the American Society of Hematology (ASH) meeting in Miami.
In a secondary endpoint in the 132-patient study, 35 percent of lisofylline patients developed GVHD, while 61 percent of placebo patients developed the disease, which occurs when the transplanted cells of the donor attack the patient's tissue and organs. Among patients treated most aggressively, the incidence of GVHD was 29 percent for the treated group and 65 percent among placebo patients.
It was reported in March that lisofylline failed to meet the primary endpoints of reducing neutropenia-related infections and mortality associated with bone-marrow transplants. James Bianco, CTI's president and CEO, said that result was due to an imbalance of high-risk patients in the treatment arms.
"While the study didn't meet its primary endpoints, it wasn't a total failure," Bianco told BioWorld Today, adding the new data will be supportive if lisofylline hits primary endpoints in subsequent pivotal trials.
That result could be very important in at least one of the studies, which involves bone-marrow transplants from unrelated donors, a procedure that results in higher incidences of severe GVHD. "We would anticipate the effect seen in this [HLA identical] population could be more dramatic in the higher-risk group," Bianco said.
The two other ongoing pivotal studies of lisofylline are in acute myelogenous leukemia (AML) and acute lung injury. A Phase IIa study also is under way, testing the compound's ability to treat mucositis in head and neck cancer patients receiving radiation and chemotherapy.
Lisofylline works by modulating selective stress-activated cell signaling pathways that respond to chemotherapy, radiation and trauma. It is designed to reduce oxidative damage to tissues.
In another presentation at the ASH meeting, CTI's head of immunology, Steven Klaus, reported that lisofylline is able to suppress the differentiation of human lymphocytes to Th1 inflammatory cells, which are critical to development of severe GVHD. And, in a third presentation on the drug, CTI's research chairman, Jack Singer, reported lisofylline patients who had a reduction in circulating oxidized lipids also showed a reduced incidence of severe GVHD.
The next data to come out of pivotal lisofylline trials will be mortality results from the lung-injury study. An interim analysis on the first 200 patients is expected in March, Bianco said. Results are due early in the summer of 1999 from a 160-patient study on the drug's ability to prevent serious infection in patients receiving chemotherapy for AML. And a 206-patient study in unmatched bone-marrow transplantation is expected to be completed late next year.
"Any of these trials, if successful for their primary endpoints, would provide a basis to file a new drug application," Bianco said.
Johnson and Johnson (J&J), of New Brunswick, N.J., has been collaborating on development of lisofylline since late 1996 and had paid CTI $37.6 million as of Sept. 30, in equity payments, license and milestone fees, and development costs. That deal was revised in July, and provided for J&J to pay development costs through 1998, after which CTI would be responsible for development. J&J still can assume responsibility for development and commercialization, following a successful Phase III trial and additional payments to CTI.
Cell Therapeutics' stock (NASDAQ:CTIC) closed Tuesday at $3.062, up $0.062. *