Bristol-Myers Squibb announced this morning that the U.S. Food and Drug Administration (FDA) has expanded its approval of Sprycel (dasatinib) tablets. The new indication includes the treatment of children with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).
In 2006, Sprycel was approved to treat adults with Philadelphia Ph+ CML in CP who were resistant or intolerant to prior therapy, including imatinib and adults with Ph+ acute lymphoblastic leukemia (ALL) who were resistant or intolerant to prior therapy. In 2010, the drug received accelerated FDA approval for the treatment of adults with newly diagnosed Ph+ CML in chronic phase. These various indications are in effect in more than 50 different countries.
CML originates in the blood-generating cells of the bone marrow, eventually invading the blood. It accounts for approximately 10% of all leukemias.
The expanded approval is based on data found in 2 pediatric studies that evaluated the safety and efficacy of the drug in 97 patients with CP-CML. Among the patients enrolled, 51 were newly diagnosed and 46 were resistant or intolerant to previous treatment with imatinib.
91 of the 97 pediatric patients were treated once daily with Sprycel tablets (60 mg/m2
; maximum dose of 100 mg once daily for patients with high body surface area) until disease progression or unacceptable toxicity. Efficacy endpoints included complete cytogenic response (CCyR), major cytogenetic response (MCyR) and major molecular response (MMR).
Median durations of the responses could not be estimated within the 4.5 year median follow-up time in newly diagnosed patients, as more than half of the responding patients had not progressed at the time of data cut-off. The same was said of the imatinib-resistant or –intolerant patients within a median follow-up 5.2 years.
“Our decision to pursue an expanded indication for Sprycel is indicative of our commitment to exploring pediatric applications within our broad development program,” said Johanna Mercier, head, U.S. Commercial, Bristol-Myers Squibb in a press release
. “We are pleased this option is now available for appropriate pediatric chronic phase CML patients and their physicians.”
Drug-related adverse events (AEs) were reported in 14.4% of Sprycel-treated pediatric patients, and the most common included myelosuppression, headache, nausea, diarrhea, skin rash, and pain in the abdomen and extremeties.
The recommended dose for Spyrcel in pediatric patients is based on body weight, but administered orally once daily, and recalculated every 3 months based on body weight, or as deemed necessary.
“While chronic myeloid leukemia is rare in children, accounting for less than three percent of all pediatric leukemias, it is often more aggressive in younger patients than in adults and until recently, there have been few available treatment options,” said Vickie Buenger, President, Coalition Against Childhood Cancer. “The FDA’s decision to approve the expanded use of Sprycel in children with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase may bring new hope to these patients and their families.”
, both the FDA and European Medicines Agency (EMA) accepted a supplemental New Drug Application (sNDA) for Bosulif (bosutinib) for the adult patient population.
Sprycel tablets have been deemed less effective when crushed, cut or chewed, and it is recommended that they are swallowed whole. The exposure in patients receiving a crushed tablet was reportedly lower than those swallowing an intact tablet.
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