FDA approves new orphan drug for chronic myelogenous leukemia

FDA approved bosutinib (Bosulif, Pfizer) to treat chronic myelogenous leukemia (CML), a blood and bone marrow disease that usually affects older adults.

An estimated 5,430 men and women will be diagnosed with CML in 2012. Most people with CML have a genetic mutation, called the Philadelphia chromosome, which causes the bone marrow to make an enzyme called tyrosine kinase. This enzyme triggers the development of too many abnormal and unhealthy white blood cells called granulocytes. Granulocytes fight infection.

“Bosulif offers an additional treatment option for patients who either do not respond or cease to respond to other CML treatments or are unable to tolerate the other available treatments,” said Mark Shapiro, MD, PhD, senior director and global medical affairs leader for hematology programs in Pfizer's Oncology Business Unit.

Bosutinib is intended for patients with chronic, accelerated, or blast phase Philadelphia chromosome positive CML who are resistant to or who cannot tolerate other therapies, including imatinib. Bosutinib works by blocking the signal of the tyrosine kinase that promotes the development of abnormal and unhealthy granulocytes.

“With the approval of tyrosine kinase inhibitors, we are seeing improvements in the treatment of CML, based on a better understanding of the molecular basis of the disease,” Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in FDA’s Center for Drug Evaluation and Research, said in a press release. “These improvements have been observed in chronic and accelerated phases of CML.”

Other drugs recently approved by FDA to treat various forms of CML include imatinib (Gleevec, Novartis) in 2001, dasatinib (Sprycel, Bristol-Myers Squibb) in 2006, and nilotinib (Tasigna, Novartis) in 2007.

The safety and effectiveness of bosutinib was evaluated in a single clinical trial that enrolled 546 adult patients who had chronic, accelerated, or blast phase CML. These patients had disease that progressed after treatment with imatinib or imatinib followed by dasatinib and/or nilotinib, or who could not tolerate the side effects of prior therapy. All patients in the trial were treated with bosutinib.

In patients with chronic phase CML, efficacy was determined by the number of patients who experienced a major cytogenetic response (MCyR) within the first 24 weeks of treatment. Results showed 34% of patients who had been previously treated with imatinib achieved MCyR after 24 weeks. Of the patients who achieved MCyR at any time, 52.8% had their response last at least 18 months. Among patients previously treated with imatinib followed by dasatinib and/or nilotinib, about 27% achieved MCyR within the first 24 weeks of treatment. Of those who achieved MCyR at any time, 51.4% had their MCyR last at least 9 months.

In patients with accelerated CML previously treated with at least imatinib, 33% had their blood counts that returned to normal range (complete hematologic response) and 55% achieved normal blood counts with no evidence of leukemia (overall hematologic response) within the first 48 weeks of treatment. Meanwhile, 15% and 28% of patients with blast phase CML achieved complete hematologic response and overall hematologic response, respectively.

The most common side effects observed in those receiving bosutinib were diarrhea, nausea, a low level of platelets in the blood (thrombocytopenia), vomiting, abdominal pain, rash, low red blood cell count (anemia), fever, and fatigue.