Bristol-Myers Squibb Company announced that the US Food and Drug Administration (FDA) has granted full approval for Sprycel (dasatinib) for the treatment of adults in all phases of chronic myeloid leukaemia (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 to 35 per cent 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:
"Sprycel helps to fulfil 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, Leukaemia 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 labelling encompasses results from seven clinical trials and more than 2,100 patients with CML or Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL). The most frequently reported serious adverse reactions with Sprycel included pleural effusion (11 per cent), gastrointestinal bleeding (4 per cent), febrile neutropenia (4 per cent), dyspnoea (3 per cent), pneumonia (3 per cent), pyrexia (3 per cent), diarrhoea (3 per cent), infection (2 per cent), congestive heart failure/cardiac dysfunction (2 per cent), pericardial effusion (1 per cent), and central nervous system (CNS) haemorrhage (1 per cent). The most frequently reported adverse reactions (reported in =20 per cent of patients) included myelosuppression, fluid retention events, diarrhoea, headache, dyspnoea, skin rash, fatigue, nausea and haemorrhage.