Nilotinib Receives FDA-approval to Treat Pediatric Patients with Chronic Phase CML

On March 22, 2018, the FDA granted Novartis approval to market TASIGNA® (nilotinib) for the treatment of pediatric patients with frontline or resistant Philadelphia chromosome positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP) [1]. CML is a disease characterized by hyper-proliferative white blood cells that harbor a chromosomal translocation resulting in a constitutively active fusion kinase, BCR-ABL1 (Ph) [2]. The pathogenesis of CML is directly driven by the BCR-ABL1 kinase, thus targeting its activity has proved to be an effective therapeutic strategy for the treatment of CML. Several tyrosine kinase inhibitors (TKIs) have been developed that inhibit the activity of BCR-ABL1 and provide clinical efficacy in both adults and children with CML. Currently, there are five TKIs that have been approved by the FDA to treat CML: imatinib (GLEEVEC®), dasatinib (SPRYCEL®), nilotinib, bosutinib (BOSULIF®), and ponatinib (ICLUSIG®); the prior three are approved for frontline treatment of CML in adults and children [1, 3-6]. Nilotinib was initially approved in 2007 for the treatment of adults with Ph+ CML who were resistant or intolerant to imatinib-based therapies and was then expanded to frontline treatment of adults with CML in 2010 [1].

Nilotinib received approval to treat pediatric patients with Ph+ CML-CP based on results of two open-label, multicenter studies investigating the safety and efficacy of nilotinib in pediatric patients older than one year of age with Ph+ CML-CP that is resistant or intolerant to imatinib or dasatinib (n=44), or who have newly diagnosed Ph+ CML-CP (n=25) (NCT01077544) (NCT01844765) [7, 8]. The major molecular response rate at 12 months was 40.9% in patients with resistant or intolerant Ph+ CML-CP and 60% in patients with newly diagnosed Ph+ CML-CP [1]. Additionally, the safety profile was found to be similar to what is observed in adults. This approval adds another agent to the pediatric CML armamentarium.

–Zachary Moore, on behalf of the Medical Content Team

1. TASIGNA® (nilotinib) capsules, for oral use. Drugs@FDA: FDA Approved Drug Products March 22, 2018 [cited 2018 May 1]; Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022068s027lbl.pdf.
2. Chereda, B. and J.V. Melo, Natural course and biology of CML. Ann Hematol, 2015. 94 Suppl 2: p. S107-21.
3. Gleevec™(imatinib mesylate)Tablets. Drugs@FDA: FDA Approved Drug Products May 20, 2003 [cited 2018 May 1]; Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/021588s001lbl.pdf.
4. SPRYCEL (dasatinib) tablets, for oral use Drugs@FDA: FDA Approved Drug Products November 9, 2017 [cited 2018 May 1]; Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021986s020lbl.pdf.
5. BOSULIF® (bosutinib) tablets, for oral use Drugs@FDA: FDA Approved Drug Products December 19, 2017 [cited 2018 May 1]; Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/203341s009lbl.pdf.
6. ICLUSIG® (ponatinib) tablets for oral use. Drugs@FDA: FDA Approved Drug Products November 28, 2016 [cited 2018 May 1]; Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203469s022lbl.pdf.
7. Open Label, Phase II Study to Evaluate Efficacy and Safety of Oral Nilotinib in Philadelphia Positive (Ph+) Chronic Myelogenous Leukemia (CML) Pediatric Patients. ClinicalTrials.gov  [cited 2018 May 1]; Available from: https://clinicaltrials.gov/ct2/show/NCT01844765.
8. A Pharmacokinetic (PK) Study of Nilotinib in Pediatric Patients With Philadelphia Chromosome-positive (Ph+) Chronic Myelogenous Leukemia (CML) or Acute Lymphoblastic Leukemia (ALL). ClinicallTrials.gov  [cited 2018 May 1]; Available from: https://clinicaltrials.gov/ct2/show/NCT01077544.