FDA Approves Tasigna for Pediatric CML

Tasigna (nilotinib) was granted Food and Drug Administration (FDA) approval, to be used in the first- and second-line setting for pediatric patients 1 year old or older who have Philadelphia chromosome—positive chronic myeloid leukemia in the chronic phase (Ph+ CML-CP).

The approval was issued based on a cohort of 69 pediatric patients with Ph+ CML-CP enrolled across two trials. Patients were either newly diagnosed or resistant/intolerant to prior treatment with a tyrosine kinase inhibitor.

The major molecular response (MMR; BCR ABL/ABL 0.1 percent or less International Scale [IS]) in newly diagnosed patients was 60 percent at 12 cycles, with 15 patients achieving MMR. The cumulative MMR in this group was 64.0 percent by cycle 12, and the median time to first MMR was 5.6 months (range, 2.7-16.6).

In the resistant/intolerant group, the MMR rate was 40.9 percent at 12 cycles, with 18 patients being in MMR. The cumulative MMR rate in this group was 47.7 percent by cycle 12, and the median time to first MMR was 2.8 months.

"Novartis' commitment to people living with CML is reinforced by today's FDA approval of Tasigna in children," Liz Barrett, CEO, Novartis Oncology, said in a statement. "This expanded use, along with the other recent global regulatory Tasigna milestones, underscores our dedication to reimagining medicine and addressing the needs for people with CML, including children with this cancer."

The safety profile was similar to that observed in adults, except for laboratory abnormalities of hyperbilirubinemia, meaning there is too much bilirubin in the blood, (grade 3/4: 13 percent) and transaminase elevation (AST grade 3/4: 1 percent, ALT grade 3/4: 9 percent), which occurred more commonly than in adult patients. There was one previously treated patient who progressed to advance phase/blast crisis after around 10 months on treatment.

Beyond the two new indications, Tasigna is approved by the FDA for the treatment of newly diagnosed adult patients with Ph+ CML-CP, as well as the treatment of CP and accelerated phase Ph+ CML in adult patients resistant to or intolerant to prior therapy that included Gleevec (imatinib)

This is the second recent major regulatory development in this patient population in the past six months. On Nov. 10, 2017, the FDA approved Sprycel (dasatinib) for the treatment of pediatric patients with Ph+ CML-CP.

The approval was based on results with Sprycel demonstrated in 97 pediatric patients with CP-CML enrolled across two studies, an open-label, nonrandomized, single-arm phase 2 trial (CA180-226; NCT00777036) and an open-label, nonrandomized, dose-ranging phase 1 trial (CA180-018; NCT00306202). Fifty-one patients (all from the single-arm trial) were newly diagnosed, and the remaining 46 (29 from the single-arm study and 17 from the dose-ranging trial) were intolerant or resistant to prior Gleevec.

At a median follow-up of 4.5 years, more than half of the responding patients in the treatment-naïve cohort had not progressed at the time of the data cutoff, and thus, the median duration of complete cytogenetic response (CCyR), major cytogenetic response (MCyR), and MMR could not be estimated. The same was true at the median follow-up time of 5.2 years for the previously treated cohort.

The range of duration of response (DOR) for the newly diagnosed patients was 2.5+ to 66.5+ months for CCyR, 1.4 to 66.5+ months for MCyR, 5.4+ to 72.5+ months for patients who achieved MMR by month 24, and 0.03+ to 72.5+ months for patients who achieved MMR at any time. The ‘+’ denotes a censored observation. Among the imatinib-intolerant cohort, the DOR ranges were 2.4 to 86.9+ months for CCyR, 2.4 to 86.9+ months for MCyR, and 2.6+ to 73.6+ months for MMR.