By Debbie Strickland
Cell Therapeutics Inc. (CTI) beat out more than half a dozen competitors to win National Institutes of Health (NIH) support for a pivotal trial of a drug to treat acute lung injury (ALI), the precursor to acute respiratory distress syndrome (ARDS).
The drug in question, lisofylline, is a small-molecule anti-inflammatory compound better known for its potential to reduce toxic side effects of cancer chemotherapy, radiation and bone marrow transplants. Its oncology applications are partnered with Johnson & Johnson, of New Brunswick, N.J., which also has an option to license the drug for the ALI indication.
The ALI Phase III trial will enroll up to 800 patients requiring mechanical ventilation for acute lung injury. Conducted with the aid of the NIH's National Heart, Lung and Blood Institute, the trial will use the agency's Acute Respiratory Distress Syndrome Network (ARDSNet) of 10 U.S. medical centers.
The collaboration offers several advantages to Seattle-based Cell Therapeutics, said James Bianco, president and CEO. ARDSNet has standardized treatment protocols across its centers, providing for consistent treatment and therefore cleaner trial results. The network also offers the prospect of faster enrollment, since each center treats about 30 ALI patients per year.
"It's almost like a high-throughput concept," said Bianco. "You couldn't ask for a better environment in which to test one agent."
Furthermore, he said, "this trial is distinctly different" from past trials in ALI and ARDS. "This is a much more homogenous group. [The study] is going to start the clock on the whole patient population within six hours."
Patients will be treated with either lisofylline or placebo within six hours of being put on a ventilator. If treatment does not begin within that period, the patient is excluded from the trial.
Drug Protects Lung Cells
As in oncology applications, lisofylline works in the lungs by protecting epithelial cells from free-radical damage, the source of which in this case is the large volume of oxygen from the ventilator.
The collaboration also confers a financial advantage, according to the CEO.
"They're paying the lion's share of the cost of the study," said Bianco, referring to the NIH.
The company expects to enroll the first 200 patients by the end of 1998. At that point, the investigators and an independent data and safety monitoring board will conduct an interim analysis to determine whether the trial shows trends toward efficacy and should continue, or whether statistical significance has been achieved and the study can be stopped and declared a success. Of course, the trial would also come to an early end if analysis fails to show a trend toward efficacy or if the drug appears unsafe.
Additional interim looks are possible at 400 and 600 patients.
If lisofylline works as hoped, it could prevent patients afflicted with ALI from progressing to the more serious acute respiratory distress syndrome (ARDS). The primary endpoint is 28-day mortality.
Compared to the higher-profile cancer indications, ALI/ARDS is a "sleeper," said Bianco. Wall Street observers have not factored this market into their valuation of the company, he said.
Also, since dosing, formulation and route of administration are similar to the oncology applications, lisofylline "can be priced competitively across both applications," he said.
In cancer, Cell Therapeutics' Phase III program is three-pronged, testing the drug in patients who undergo high-dose chemotherapy and/or radiation and receive bone marrow transplants from matched-related and matched-unrelated donors, and in patients with acute myeloid leukemia. The company expects to file a new drug application this year based on results from a completed Phase III trial in bone-marrow transplant patients with matched donors.
The firm will seek as broad a label as possible, said Lee Parker, vice president for investor relations.
Cell Therapeutics also has advanced to the clinical level CT-2584 — a small molecule drug for patients with multidrug-resistant cancer, including prostate cancer and sarcomas. CT-2584 is undergoing Phase I trials, with a Phase II trial for advanced refractory prostate cancer expected to begin in early 1998.
In addition to its centerpiece Johnson & Johnson collaboration, Cell Therapeutics has an agreement with BioChem Pharma Inc., of Laval, Quebec, that grants BioChem Canadian commercialization rights to both lisofylline and CT-2584.
Cell Therapeutics' shares (NASDAQ:CTIC) closed Friday at $12.875, up $0.875. *