AnorMed Inc. got the go-ahead from the FDA Thursday to begin two pivotal Phase III trials of its stem cell-mobilizing agent, AMD3100, for stem cell transplantation in cancer patients.

The Vancouver, British Columbia-based company mapped out a plan for the trials under a special protocol assessment agreement with the FDA. It started the trials immediately and is enrolling 600 patients.

"We hope the results will show that using AMD3100 with [granulocyte-colony stimulating factor] results in more patients getting more cells in less time," said Elisabeth Whiting, AnorMed's vice president of corporate development.

Stem cell transplantation is used to restore the immune system of patients who have had chemotherapy to treat hematologic cancers, such as multiple myeloma and non-Hodgkin's lymphoma (NHL). The number of cells available for transplantation is the strongest predictor of success in transplantation.

About 45,000 stem cell transplantations are performed each year worldwide. AMD3100 could help reduce supportive care costs by reducing the number of apheresis sessions and the need for remobilization. For AnorMed, the product could mean a minimum of $200 million each year in worldwide sales.

Granulocyte-colony stimulating factor (G-CSF) is used to help patient stem cells multiply prior to collection. By adding AMD3100 to the mix, doctors are able to mobilize and move the cells where they are more accessible. AMD3100 could help reduce the number of times cell collection is necessary.

"AMD3100 is injected subcutaneously. It's a single injection and it causes the stem cells to move out of the bone marrow and into the circulating bloodstream," Whiting told BioWorld Today.

Phase II data in more than 100 NHL and multiple myeloma patients show AMD3100 increases the number of stem cells available for transplantation. Clinical studies also have shown the drug has a good safety profile. The product blocks a specific cellular receptor that triggers the movement of stem cells.

The Phase III trials are powered to show at least a 20 percent difference between the study arms, one using AMD3100 plus G-CSF and the other using G-CSF with placebo. The randomized, double-blind, placebo-controlled trials will enroll 300 patients with NHL and 300 with multiple myeloma, all of whom are undergoing autologous stem cell transplantation.

Both studies will evaluate AMD3100's ability to provide a rapid increase in the number of peripheral blood stem cells capable of engraftment, as well as an increase in the proportion of patients reaching a peripheral blood stem cell target. Researchers also will look at its ability to reduce the number of apheresis sessions needed to reach that target. In the NHL study, the stem cell collection target is 5 million CD34+ cells per kilogram of patient body weight within four days of apheresis. In the multiple myeloma study, it is 6 million cells per kilogram of body weight within two days of apheresis.

AnorMed will conduct the study at more than 30 centers throughout the U.S. If accrual goes as planned, patient recruitment should be complete with three-month follow-up data available in 2006. The company has not announced a target date for a new drug application filing. AnorMed owns all rights to the product, and also is conducting clinical studies in Germany. It plans to soon initiate a program in Canada.

"We're evaluating selling the drug ourselves in North America," Whiting said. "We would likely seek a marketing partner for Europe."

The Phase III trials will cost AnorMed about $20 million, which the company intends to pay for with money attained from Shire Pharmaceuticals Group plc, of Basingstoke, UK. The October FDA approval of Shire's Fosrenol for hyperphosphatemia triggered an $18 million payment to AnorMed, which owned the Fosrenol patents before Shire acquired them in March. AnorMed also is entitled to another $7 million if the product is approved in the European Union. (See BioWorld Today, March 24, 2004, and Oct. 28, 2004.)

AnorMed expects to present new data from ongoing Phase II studies of AMD3100 at the American Society of Hematology conference, which begins this weekend in San Diego.

The company's stock (TSE:AOM) dropped C50 cents on Thursday, to close at C$5.85 (US$4.89).

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