By Debbie Strickland

It's usually cause for celebration when a biotechnology firm slam dunks its primary efficacy endpoint in a Phase III clinical trial, but a patent infringement action from a big pharma company with a similar product is keeping the champagne corked at CellPro Inc.

The Bothell, Wash., firm first received FDA marketing approval of the Ceprate SC Stem Cell Concentration System in December 1996 as a means of processing autologous bone marrow to obtain a stem cell-enriched population for hematopoietic support after myeloablative therapy.

The indication evaluated in this latest Phase III trial -- pre-chemotherapy selection of peripheral blood stem cells in patients' multiple myeloma -- could turn the product into a tumor cell-purging blockbuster. That's because oncologists could regard the labeling as "proof of principle" and apply the technique to patients undergoing high-dose chemotherapy for other cancers.

"This would let us go out and market the product for the purpose people want to use it for: purging tumor cells and retaining stem cells," said CellPro spokeswoman Joann Reiter.

But for now, a cloud hangs over the company and its machine. Baxter International Inc., of Deerfield, Ill., whose Isolex cell-separation system goes before an FDA advisory panel this summer, has argued CellPro's product infringes patents held by Baxter, Becton Dickinson & Co., of Franklin Lakes, N.J., and Johns Hopkins University, of Baltimore.

A jury ruled in CellPro's favor, but a U.S. District judge overturned the verdict and agreed with Baxter and its co-plaintiffs. CellPro has appealed.

Baxter and VIMRX Pharmaceuticals Inc., of Wilmington, Del., have meanwhile formed a new company to manage and develop the Isolex cell-separation technology. (See BioWorld Today, June 16, 1997, p. 1.)

In Ceprate's 15-center, 134-patient Phase III trial, the primary endpoint was to show greater than a 2-log reduction in the number of cells in the stem-cell-enriched product. Evaluated in Ceprate-treated patients who had a clonable tumor sequence, the endpoint was achieved, with a mean 3.3-log reduction -- or greater than 99.9 percent -- of contaminating myeloma cells.

Fifty-four percent of Ceprate-treated patients received a stem cell product with no detectable tumor cells, compared to 14 percent of comparable patients who received an unselected apheresis product.

The primary safety endpoint of successful neutrophil engraftment by day 14 also was achieved. Analysis of four secondary endpoints for overall safety assessment revealed no significant statistical differences for three endpoints: time to neutrophil engraftment, incidence of infections and overall survival. Analysis of a fourth endpoint, time to platelet engraftment, revealed a statistically significant difference (11 days in patients receiving Ceprate-selected cells vs. nine days in patients receiving unselected cells).

The difference, according to the company, was related to the number of stem cells infused and the platelet count of the patient prior to collection.

CellPro noted that patients who received 4 million or more stem cells per kilogram had rapid engraftment, with no significant difference between the study arms. The company plans to propose labeling that advises the user of the threshold number of stem cells and the relationship to time to platelet engraftment.

"We are delighted with the trial results, which represent a significant milestone in our efforts to provide new applications and products for cell selection," said Richard Murdock, president and CEO.

The results are being presented this week at the VI International Workshop on Multiple Myeloma, in Boston.

Investors reacted cautiously to CellPro's clinical trial success. Following the announcement Monday, the company's shares (NASDAQ:CPRO) closed at $6.625, up $0.500. Tuesday the stock closed unchanged.

Financial analysts who watch the company remain optimistic about CellPro's prospects.

"The [lawsuit] overlays everything with regard to CellPro, but the clinical trial itself was quite positive," said analyst Marc Ostro, of UBS Securities, in New York.

In a "normal world," the data would boost the stock's price, said Ostro, but "given the still unresolved patent issues, the market has taken a very cautious approach to using this data to increase the valuation of the company."

Sales of Ceprate likely will continue, he said. Even if Baxter wins an injunction, the federal government could intervene under the Bayh-Dole Act and order Baxter to grant CellPro a non-exclusive license.

"There's a lot of pressure to keep this life-saving product on the market," said Ostro, noting lobbying efforts from politicians, the public and the American Cancer Society.

On Tuesday, both UBS Securities and Hambrecht & Quist LLC, also of New York, recommended CellPro's stock.

"We believe that these are the most significant and positive data that CellPro has ever released," wrote Richard van den Broek, of Hambrecht & Quist. "CellPro's device provides a crucial incremental benefit to the existing transplant market." *