Pixantrone (pick-san-trone) (BBR 2778) is a new chemical compound being developed for the treatment of non-Hodgkin’s lymphoma (NHL), and various other hematologic malignancies, solid tumors, and immunological disorders. It is being developed to improve the activity and safety in treating cancers usually treated with the anthracycline family of anti-cancer agents.
Anthracyclines have been shown to be very clinically active in a number of tumor types, such as lymphoma, leukemia, and breast cancer. For these diseases, anthracycline-containing chemotherapy regimens are effective in first-line (initial) treatment. Pixantrone is a novel DNA major groove binder with an aza-anthracenedione molecular structure, differentiating it from anthracycline chemotherapy agents.
The cardiac toxicity of anthracyclines often prevents their repeat use in patients who relapse after first-line anthracycline treatment. As a result, chemotherapy regimens that do not include anthracyclines often are used for the second-line treatment of relapsed NHL. There are no drugs approved in the United States for second- or third-line treatment for patients with relapsed aggressive NHL.
Pixantrone has been designed to reduce the potential for these severe cardiotoxicities, as well as to potentially increase activity and simplify administration compared to the currently marketed anthracyclines. Pixantrone could allow repeat therapy in relapsed patients and combination therapy with a broader range of chemotherapies. Pixantrone also is easier to administer than anthracyclines. This is because it is less likely to cause tissue damage and can be administered through a peripheral vein, eliminating the need for a central line.
We are focusing resources on obtaining pixantrone approval based on the EXTEND (PIX301) phase III clinical trial of pixantrone for patients with relapsed aggressive NHL. Enrollment is complete in this trial, and in November 2008 we announced that this trial achieved the primary efficacy endpoint based on a preliminary intent to treat efficacy analysis. Further evaluation of additional details of the study will provide complete safety and progression-free survival information.
Pre-New Drug Application (NDA) discussion with the United States Food and Drug Administration (FDA) is planned for early 2009. The data could provide a registration path for pixantrone, if final study results are adequate, for submitting an NDA with the FDA in early 2009.
The FDA has granted fast track designation for pixantrone for the treatment of relapsed or refractory indolent NHL and relapsed aggressive NHL.