Using its priority review pathway, the US Food and Drug Administration (FDA) approved the monoclonal antibody obinutuzumab (Gazyva; Genentech) for the treatment of patients with chronic lymphocytic leukemia (CLL) who have not previously received treatment for CLL. Obinutuzumab is approved to be used in combination with chlorambucil.
Obinutuzumab, which works by helping immune system cells to attack cancer cells, is the first drug with a “breakthrough therapy” designation to receive FDA approval; other breakthrough therapies are currently under FDA review for different types of cancers.
“Today’s approval represents an important new addition to the treatments for patients with CLL,” said Richard Pazdur, MD, Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “This approval reflects the promise of the Breakthrough Therapy Designation program, allowing us to work collaboratively with companies to expedite the development, review and availability of important new drugs.”
Obinutuzumab also has an orphan drug designation, because CLL is categorized as a rare disease. According to the National Cancer Institute, 15,680 Americans are expected to be diagnosed with CLL in 2013 and 4580 will die from it.
Obinutuzumab’s approval was based on an open-label multicenter trial of 356 treatment-naïve patients with CLL who were randomized to obinutuzumab in combination with chlorambucil or to chlorambucil alone. The combination of obinutuzumab plus chlorambucil demonstrated a significant, 2-fold improvement in progression-free survival compared with chlorambucil alone, for an average of 23 months with the combination versus 11.1 months in the monotherapy cohort.
The most common adverse events in patients receiving obinutuzumab were infusion-related reactions, neutropenia, thrombocytopenia, anemia, musculoskeletal pain, and fever.
Gazyva was approved with a boxed warning regarding the risk for hepatitis B virus (HBV) reactivation and progressive multifocal leukoencephalopathy, a rare brain disorder; these are known risks with other monoclonal antibodies. Patients should be advised of these risks and be assessed for HBV risk and reactivation risk. (November 1, 2013)
