By Lisa Seachrist
ROCKVILLE, Md. — An FDA advisory panel unanimously recommended that CellPro Inc.'s stem cell concentration device receive an expanded label to include its ability to concentrate stem cells from peripheral blood as a support for myeloablative chemotherapy.
The Biological Response Modifiers Advisory Committee voted 11 to 0 to expand the label as a selection device for stem cells from peripheral blood used to regenerate the hematopoetic potential of bone marrow following very high dose chemotherapy. The committee, however, was divided as to whether the results presented could be generalized to a wide variety of cancers.
"This company has done a very good job showing that this product does reduce the number of cells [100 fold]," said Virginia Broudy, associate professor of medicine at the University of Washington, in Seattle. "I think they should be commended for their work."
"I was very pleased with the outcome and vote of this meeting," said Richard Murdock, CEO of Bothell, Wash.-based CellPro. "Peripheral blood is the major indication for us. It has indications for lymphoma and other malignancies."
The company's stock (NASDAQ:CPRO) gained 58 percent Tuesday, closing at $5.125, an increase of $1.875.
CellPro 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 hematopoetic support after myeloablative therapy.
The indication considered by the advisory panel Tuesday was the pre-chemotherapy selection of peripheral blood stem cells in patients with multiple myeloma who are about to undergo a myeloablative chemotherapy regime. Presumably, the Ceprate System benefits patients by concentrating progenitor cells, resulting in a smaller number of tumor cells being returned to the patients.
Label Expansion Could Make Device A Blockbuster
Expansion of the label to include this indication could turn the product into a blockbuster tumor-cell-purging device, because physicians are likely to regard the labeling as "proof of principle" and use the technique for patients undergoing high-dose chemotherapy for other cancers.
CellPro presented data from a 15-center, 131-patient randomized Phase III trial designed to show greater than a two-log reduction in the number of total cells in the stem-cell-enriched product in comparison with the product of simple leukopharesis. All patients had blood collected and filtered to provide white blood cells. Half of the trial participants had stem cells (CD34+ cells) concentrated with the Ceprate System.
Patients who received a Ceprate-treated product achieved a two-log reduction in the number of total cells and showed neutrophil engraftment in 14 days. In addition, 54 percent of the treated patients received CD34+ cells with no detectable tumor cells while only 14 percent of the control group received such a product.
"This is the first definitive tumor purging trial," Murdock said. "We worked extensively with FDA to design this trial. We know that with malignancies, tumor purging really improves the overall outlook. We will be following the trial participants for the long term."
Ceprate-treated patients were more likely to experience a delay in platelet engraftment compared with the control group. The company attributed the delay to the number of stem cells infused and the platelet count of patients prior to stem cell collection. As a result, the advisory panel recommended a label note that platelet engraftment is likely to be slowed in patients who receive fewer than 2 million CD34+ cells.
"The label should spell out that patients need the [2 million cells]," Broudy said, "because it is very clear that below that threshold platelets are slower to engraft."
Aside from concerns about platelet engraftment, the panel was divided on whether the label should specifically apply to multiple myeloma patients or be generalized as a way to concentrate stem cells for a variety of malignancies.
"I would say that it depletes myeloma cells," Broudy said. "That is what the company so elegantly and convincingly showed."
However, panel member Jonathan Silver, senior investigator at the National Institute of Allergy and Infectious Diseases in Bethesda, argued the underlying biological principle was likely to be the same for multiple myeloma and other malignancies, so the label should not be restricted.
In addition, several panel members observed the restrictive label may prevent insurance companies from paying for the procedure, making it difficult for patients to participate in clinical trials.
"We need to keep this label generalized," said Eugenie Kleinerman, professor of cell biology and pediatrics at the University of Texas M.D. Anderson Cancer Center in Houston, Texas. "Because patients need a way to pay for the procedure. We can't conduct clinical trials if the patients won't enroll."
As encouraging as the results of the panel meeting were, CellPro continues to be involved in a patent dispute over the technology. Baxter International Inc., of Deerfield, Ill., whose Isolex cell-separation system is pending at FDA, has argued CellPro's product infringes upon patents held by Baxter; Becton Dickinson & Co., of Franklin Lakes, N.J.; and Johns Hopkins University, in Baltimore.
A jury ruled in CellPro's favor, but a U.S. district judge overturned the verdict and agreed with Baxter. Murdock noted the case is now in U.S. Appeals Court and arguments are expected to begin in May.
In addition, a shareholder class action lawsuit was filed against the company this month based on the district judge's comments in the patent case.
"The lawsuit is based entirely on the patent case and the virulent rulings that came from the judge," Murdock said. "We hope the patent case is finished at the end of this year. We really haven't had time to look at the shareholder lawsuit." *