Protein Design Labs Announces Positive Phase III Clinical Results With Zamyl(TM) for Acute Myeloid Leukemia; Plans to File BLA
FREMONT, Calif., Dec. 7 /PRNewswire/ -- Protein Design Labs, Inc. (PDL) (Nasdaq: PDLI - news) today announced positive clinical results from the Phase III trial of its humanized antibody Zamyl (SMART(TM) M195) in patients with acute myeloid leukemia (AML). The trial compared treatment with Zamyl plus a standardized chemotherapy regimen to treatment with chemotherapy alone in patients who had failed to achieve complete remission with initial therapy, or who had relapsed within one year of achieving complete remission. An initial review of the data by PDL indicates that Zamyl increased the overall response rate to 43% in the Zamyl plus chemotherapy patients (n=94) from 26% in the chemotherapy alone patients (n=97)(p=0.015), when all evaluable patients were analyzed on an intent-to-treat basis.
Certain subgroup analyses have also been performed, with a higher response rate seen in patients with longer initial complete remissions. For patients who had failed to achieve complete remission or had relapsed within six months of their first complete remission, the overall response rate was 32% in the Zamyl plus chemotherapy group (n=66), compared with 21% in the chemotherapy alone group (n=66)(p=0.237). However, for patients who had relapsed 7 to 12 months after their first complete remission, the overall response rate was 68% in the Zamyl plus chemotherapy group (n=28), significantly higher than the 35% overall response rate in the chemotherapy alone group (n=31)(p=0.019).
In this analysis, minimal requirements for an overall response were a bone marrow biopsy that demonstrated 5% or fewer blast cells and transfusion independence. The overall response category included patients who made a complete hematologic recovery as well as patients whose platelet counts were less than 100,000 per cubic millimeter. Patients were classified according to this definition without knowledge of their respective treatment assignments. This overall response criterion has been used in previous studies in acute myeloid leukemia evaluating the drug Mylotarg® (gemtuzumab ozogamicin). The data were also analyzed based upon a more stringent definition of complete response, which required complete hematological recovery, including a normal platelet and absolute neutrophil count and transfusion independence. This analysis showed a positive trend, with a complete response rate of 30% in the Zamyl plus chemotherapy arm compared with 21% in the chemotherapy alone arm (p=0.182) in the intent-to-treat analysis of all patients. A further analysis that required the complete response to occur within 70 days of the initiation of therapy, which was the prospectively defined primary endpoint of the trial, did not demonstrate statistically significant differences between the two arms of the trial.
Eric J. Feldman, M.D., Director of the Leukemia Program, Cornell University Medical Center - New York Presbyterian Hospital, and the lead investigator in the trial, will present the initial data today during a PDL-sponsored corporate symposium at the 43rd Annual Meeting of the American Society of Hematology (ASH) in Orlando, Fla.
``The preliminary data in the Phase III trial indicate that the antibody was well tolerated and was active in myeloid leukemia patients who had failed chemotherapy or had relapsed following chemotherapy,'' Dr. Feldman said. ``The 43% overall response rate in patients receiving Zamyl in the intent-to-treat analysis of all patients is particularly impressive, since more than two-thirds of the patients were in the poor prognosis group that had failed to achieve remission or relapsed within six months of their first remission.''
Only a limited analysis of adverse events occurring in this trial has been completed to date. In this preliminary review, serious adverse events occurred with greater frequency in patients receiving Zamyl plus chemotherapy (66 of 94 patients, 70%) than in patients receiving chemotherapy alone (49 of 97 patients, 50%)(p=0.005). However, investigators attributed the serious adverse events to Zamyl therapy in only 13 of these 66 patients. No significant differences for serious adverse events were seen between treatment groups for any body system. Further, the mortality during induction therapy, defined as the first 70 days after initiation of therapy, was similar for the Zamyl plus chemotherapy (15%) and chemotherapy alone (13%) groups.
Laurence Jay Korn, Ph.D., Chief Executive Officer and Chairperson, PDL, said, ``We are delighted by the positive results we have seen in this trial, and the potential benefits Zamyl might provide to myeloid leukemia patients. If the complete analysis of the data, which PDL will be conducting over the next two to three months, confirms this preliminary review, PDL plans to hold discussions with the FDA and European regulatory authorities. We would then plan to file for marketing clearance for Zamyl in the United States and Europe. If the FDA allows us to file and approves the drug, Zamyl would become PDL's first directly marketed product.''
PDL intends to manufacture Zamyl on a commercial scale in its existing manufacturing facility at Plymouth, Minn. The facility is currently undergoing renovation to accommodate commercial production. The renovations are expected to be complete in the second half of 2002, following which PDL will manufacture the qualification lots of Zamyl required for completion of a Biologic License Application (BLA). PDL currently anticipates completing the filing of a BLA in the second half of 2003.
Daniel J. Levitt, M.D., Ph.D., President, Research and Development, PDL, said, ``We believe these results are quite impressive. The majority of these patients had poor prognoses by virtue of their initial experience with chemotherapy; they were either refractory to treatment or had relapsed within six months. Although the overall response rate in the chemotherapy alone arm was actually better than we were expecting based upon previous trials, the addition of Zamyl improved the overall response rate by 65%.''
Zamyl is a humanized antibody that binds to the CD33 antigen on myeloid leukemia cells. It is the humanized version of the murine M195 monoclonal antibody, licensed by PDL from Memorial Sloan-Kettering Cancer Center in 1989.
Patients diagnosed with acute myelogenous leukemia who have relapsed after initial chemotherapy currently have low response and long-term survival rates, even when treated with additional, intensive chemotherapy. According to the American Cancer Society, there are an estimated 10,000 new cases and 6,900 deaths due to the disease in the United States on an annual basis... |
