FDA Approves Nilotinib Tablets Without Mealtime Restrictions for CML

FDA

The FDA has approved nilotinib (Danziten) tablets with no mealtime restrictions for the treatment of adult patients with newly diagnosed Philadelphia chromosome (Ph)–positive chronic myeloid leukemia (CML) in chronic phase (CP-CML); and adult patients with CP- and acute phase (AP)–CML resistant or intolerant to prior therapy that included imatinib (Gleevec).¹

Nilotinib (Tasigna) was initially approved by the FDA in 2007 for the treatment of adult patients with Ph-positive CP- and AP-CML who were resistant or intolerant to prior therapy that included imatinib.² In 2010, the agent was approved in another indication for the treatment of adult patients with newly diagnosed Ph-positive CP-CML.

"Danziten offers a new nilotinib treatment option with the equivalent efficacy to Tasigna, but without the fasting requirements of Tasigna," Richard Blackburn, chief executive officer of Azurity Pharmaceuticals, stated in a news release.¹ "Unlike Tasigna, the boxed warning on the Danziten label has no requirement for patients to take their medication in a fasted state, liberating CML patients from mealtime restrictions."

The prescribing information for Tasigna specifies that patients should avoid food for 2 hours prior to treatment and 1 hour after treatment.² Azurity Pharmaceuticals—the developer of Danziten—noted that the bioavailability of Tasigna varies, and this bioavailability increases when the agent is taken with food.¹ When taken with food, Tasigna could lead to a significantly prolonged QT interval.

As a re-engineered formulation of nilotinib, Danziten features improved bioavailability that allows for a lower dose and its consumption without mealtime restrictions without compromising the efficacy displayed by Tasigna. Danziten has demonstrated consistent pharmacokinetics without clinically significant differences in nilotinib exposure, irrespective of fasting state or meal type.

The phase 3 ENESTnd (NCT00471497) and the phase 1/2 Study A2101 (NCT00109707) supported the respective approvals of Tasigna in newly diagnosed Ph-positive CP-CML and pretreated CP- or AP-CML; both trials are listed in the clinical trial evidence in the prescribing information for Danziten.³

Data from ENESTnd showed that patients treated with nilotinib (n = 282) experienced a 12-month major molecular response (MRR) rate of 44% (95% CI, 38.4%-50.3%) compared with 22% (95% CI, 17.6%-27.6%) for those given imatinib (n = 283; P < .0001). The 24-month MMR rates were 62% (95% CI, 55.8%-67.4%) and 38% (95% CI, 31.8%-43.4%), respectively. At 60 months, 77% of patients in the nilotinib arm achieved a MRR vs 60% of patients in the imatinib arm.

Data from the single-arm Study A2101 demonstrated that nilotinib elicited an unconfirmed major cytogenetic response (MCyR) rate of 51% (95% CI, 46%-57%) in patients with resistant or intolerant Ph-positive CP- or AP-CML (n = 321). The complete and partial CyR rates were 37% (95% CI, 32%-42%) and 15% (95% CI, 11%-19%), respectively. The confirmed hematologic response rate was 39% (95% CI, 31%-48%).

References

1. Azurity Pharmaceuticals, Inc. announces FDA approval of Danziten (nilotinib) tablets, the first and only nilotinib with no mealtime restrictions. News release. Azurity Pharmaceuticals. November 14, 2024. Accessed November 14, 2024. https://azurity.com/azurity-pharmaceuticals-inc-announces-fda-approval-of-danziten-nilotinib-tablets-the-first-and-only-nilotinib-with-no-mealtime-restrictions/
2. Tasigna. Novartis. Updated June 2010. Accessed November 14, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022068s004s005lbl.pdf
3. Danziten. Azurity Pharmaceuticals. November 2024. Accessed November 14, 2024. https://danziten.com/wp-content/uploads/2024/11/Danziten-Prescribing-Information.pdf