Novartis has announced that the European Commission (EC) approved Tasigna (nilotinib) for the treatment of pediatric patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in the chronic phase (Ph+ CML-CP) and pediatric patients with Ph+ CML-CP with resistance or intolerance to prior therapy including imatinib. Tasigna is the only second-generation tyrosine kinase inhibitor (TKI) currently approved in the European Union (EU) for the treatment of Ph+ CML-CP in children. The approval follows a positive opinion issued by the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) on September 14, 2017 and applies to all EU member states.
"Treatment options for children with CML have historically been limited, and with this new indication an unmet need has been addressed," said Bruno Strigini, chief executive officer, Novartis Oncology. "Data from two prospective studies demonstrated Tasigna is safe and effective in patients as young as two years old, which is consistent with the established safety profile of Tasigna in adults."
This expanded indication is based on two prospective studies of nilotinib in children with Ph+ CML-CP, which were part of a formal "pediatric investigation plan" agreed upon with the EMA. A total of 69 pediatric patients received nilotinib. These pediatric patients were aged 2 to 18 years and diagnosed with either newly diagnosed Ph+ CML-CP or Ph+ CML-CP with resistance or intolerance to prior therapy including imatinib. In the newly diagnosed CML patients, the major molecular response (MMR; BCR ABL/ABL <=0.1% International Scale [IS]) rate was 60.0% (95% confidence interval [CI]: 38.7, 78.9) at 12 cycles, with 15 patients achieving MMR. In patients with resistance or intolerance to prior therapy including imatinib, the MMR rate was 40.9% (95% CI: 26.3, 56.8) at 12 cycles, with 18 patients being in MMR. In newly diagnosed CML patients, the cumulative MMR rate was 64.0% by cycle 12. In patients with resistance or intolerance to prior therapy including imatinib, the cumulative MMR rate was 47.7% by cycle 12.
In pediatric patients, adverse reactions observed were generally consistent with those observed in adults, with the exception of hyperbilirubinemia (Grade 3/4: 13.0%), a condition where there is too much bilirubin in the blood, and transaminase elevation (AST Grade 3/4: 1.4%, ALT Grade 3/4: 8.7%) which were reported at a higher frequency than in adult patients. No deaths were reported on treatment or after treatment discontinuation in both studies.
This is the latest in a series of regulatory milestones for Tasigna. In June, Novartis achieved an important milestone for the Ph+ CML community when Tasigna became the first and only TKI to include information on stopping therapy in adult patients with Ph+ CML-CP in both the first-line setting and after switching from imatinib in the EU label and several other labels throughout the world. Novartis continues to follow the science to advance and reimagine the future of CML.