By Mary Welch

Protein Design Labs Inc. will start its first-ever Phase III trial as its SMART (humanized) M195 antibody will enter a pivotal study for the treatment of acute myelogenous leukemia (AML).

"This is our first full-fledged Phase III trial of a product that we've developed and will conduct the Phase III trials ourselves," said Robert Kirkman, PDL's vice president of business development and corporate communications. "Of course we have a product on the market, Zenapax, but our partner, Roche, conducted those trials."

Zenapax was approved for the prevention of acute graft rejection in kidney transplant recipients and is being marketed by F. Hoffmann-La Roche AG, of Basel, Switzerland.

The Fremont, Calif.-based company will treat up to 200 patients with refractory or first-relapsed AML with a regimen of either the SMART M195 antibody plus standard chemotherapy or standard chemotherapy alone. The primary endpoint is frequency of complete remission. Secondary endpoints include frequency of partial response, duration of response and duration of overall and progression-free survival. Typically, patients in remission after chemotherapy relapse within six to nine months.

A complete remission is defined as leukemia cells making up less than 5 percent of all cells found in a patient's bone marrow 30 days following treatment. A bone marrow biopsy is conducted to determine the degree of remission.

The study design allows for an interim analysis to be conducted by an independent data safety monitory board after 60 patients (30 per arm) have been randomized and completed the initial phase of treatment. If the interim data show a highly favorable or highly unfavorably response rate, the study could be terminated.

"We don't want to give out timetables but if everything goes well, we might be looking for an opinion of the monitoring board by around the end of next year - and that's a big around," Kirkman said.

The humanized SMART M195 antibody binds to the CD33 antigen on myeloid leukemia cells. SMART antibodies combine the binding site of a mouse antibody, the small part of the antibody that attaches to its target, with about 90 percent of a human antibody. Because so little of the mouse antibody is used, there are no immune responses commonly found with mouse antibodies, the company said.

Earlier this year the company released preliminary results of a Phase II trial that showed that, over a two-month period, two patients had complete responses and one had a partial response. In addition, six of the 33 evaluable patients had substantially reduced cancer cell burden in their bone marrow.

SMART M195 is also in a Phase II trial in patients with myelodysplastic syndrome, a condition that can lead to AML, and in acute promyelocytic leukemia. A Phase II/III trial using the SMART M195 antibody to prolong remission in elderly AML patients was terminated because of slow enrollment.

"There are no plans to take the acute promyelocytic leukemia trial further," Kirkland said. "It's a very small patient population. As for the myelodysplastic syndrome trials, which are going on in Europe, there are no plans at the moment but we will wait until we're further along in this trial to decide."

SMART M195 is unpartnered in North America and Europe but is partnered in certain parts of Asia to Nippon Organon KK, of Tokyo.

Protein Design Labs' stock (NASDAQ:PDLI) closed Tuesday at $39, up 31.25 cents.