FDA grants full approval for Sprycel (dasatinib) for chronic myeloid leukemia

May 27 2009

Bristol-Myers Squibb Company has announced that the U.S. Food and Drug Administration (FDA) has granted full approval for Sprycel (dasatinib) for the treatment of adults in all phases of chronic myeloid leukemia (CML) (chronic, accelerated, or myeloid or lymphoid blast phase) with resistance or intolerance to prior therapy including Gleevec (imatinib mesylate).

Sprycel, an oral tyrosine kinase inhibitor, was originally approved under the accelerated approval regulations of Subpart H for new drugs for serious or life-threatening illnesses of the Food, Drug and Cosmetic Act, based on its effectiveness on hematologic and cytogenetic response rates in CML.

The full approval was based in part on results from a Phase 3 randomized, open-label dose-optimization study that enrolled 670 chronic phase CML patients with resistance or intolerance to Gleevec. The primary endpoint of this study was major cytogenetic response (MCyR) (0-35 percent Ph+ metaphases, which combines both complete and partial responses), in Gleevec-resistant patients. The data included a minimum of two years of follow up after the start of treatment with Sprycel 100 mg once daily, which is the recommended starting dose of Sprycel for chronic phase CML patients resistant or intolerant to Gleevec. A summary of results from the 167 patients who received Sprycel 100 mg once daily include:

• 80 percent progression-free survival (95% CI: 73%-87%) estimated rate at two years, based on Kaplan-Meier estimates
• 91 percent overall survival (95% CI: 86%-96%) estimated rate at two years, based on Kaplan-Meier estimates
• 63 percent of patients achieved MCyR (95% CI: 56%-71%; median duration of treatment was 22 months)
• 93 percent of patients who achieved MCyR maintained that response for 18 months (95% CI: 88%-98%), based on Kaplan-Meier estimates

“Sprycel helps to fulfill a need for second-line treatments for CML patients with resistance or intolerance to Gleevec. The two-year follow-up data further support the use of Sprycel as an important treatment option for this patient population,” said Dr. Hagop Kantarjian, Chairman and Professor, Leukemia Department, MD Anderson Cancer Center.

The approved label also now includes a new recommended starting dosage of Sprycel (dasatinib) 140 mg once daily for accelerated, myeloid blast and lymphoid blast phase CML resistant or intolerant to prior therapy including Gleevec and Ph+ ALL resistant or intolerant to prior therapy.

Safety data in the labeling encompasses results from seven clinical trials and more than 2,100 patients with CML or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). The most frequently reported serious adverse reactions with Sprycel included pleural effusion (11%), gastrointestinal bleeding (4%), febrile neutropenia (4%), dyspnea (3%), pneumonia (3%), pyrexia (3%), diarrhea (3%), infection (2%), congestive heart failure/cardiac dysfunction (2%), pericardial effusion (1%), and central nervous system (CNS) hemorrhage (1%). The most frequently reported adverse reactions (reported in ≥20% of patients) included myelosuppression, fluid retention events, diarrhea, headache, dyspnea, skin rash, fatigue, nausea and hemorrhage.