FDA Accepts NDA for Nilotinib Biosimilar XS003 for Chronic Myeloid Leukemia

The FDA has accepted a new drug application (NDA) seeking the approval of XS003, biosimilar referencing nilotinib (Tasigna), for the treatment of patients with chronic myeloid leukemia (CML).1

Initially approved by the FDA in 2007, nilotinib is currently indicated for the treatment of:2

1. Adult and pediatric patients 1 year of age and older with newly diagnosed, Philadelphia chromosome (Ph)–positive CML in chronic phase (CP-CML).
2. Adult patients with CP-CML and CML in accelerated phase (AP-CML) resistant to or intolerant to prior therapy that included imatinib (Gleevec).
3. Pediatric patients 1 year of age and older with Ph-positive CP-CML-CP and AP-CML resistant or intolerant to prior TKI therapy.

Developed using Xspray Pharma’s proprietary HyNap technology, XS003 demonstrated bioequivalence to the reference product at less than half the dose, according to data from registration studies.1 The formulation also showed a significantly reduced food effect—29% compared with 82% for nilotinib—suggesting that XS003 may be taken with or without food, pending FDA review of final labeling and related warnings

“The FDA’s decision to accept our NDA for review marks an important milestone,” Per Andersson, chief executive officer of Xspray Pharma, stated in a news release. “With 2 product candidates under FDA review, we are demonstrating that the HyNap platform has broad applicability and the potential to deliver more improved TKIs to the market.”

In November 2024, the FDA approved of another formulation of nilotinib (Danziten) tablets with no mealtime restrictions for the treatment of adult patients with newly diagnosed, Ph-positive CP-CML; and adult patients with CP-CML and AP-CML resistant or intolerant to prior therapy that included imatinib.3

The NDA for XS003 is supported by pharmacokinetic data showing that the biosimilar maintained therapeutic exposure and offered improved dose linearity, allowing for more predictable dose adjustments and potentially greater safety.1 The reduced food effect may also enhance patient adherence by eliminating the need for fasting before administration and could reduce risks associated with QTc prolongation and other adverse effects noted in the reference product’s boxed warning.

The current prescribing information for nilotinib advises patients to avoid food for 2 hours before and 1 hour after each dose.2 The development of XS003 aims to address these limitations, providing a more convenient and potentially safer formulation for patients receiving long-term TKI therapy.1

“Since the FDA now has a solid understanding of our manufacturing process, I am confident that the upcoming pre-approval inspection will be completed without observations. It is essentially the same process that has previously been inspected. Furthermore, we are working closely with the manufacturer to ensure that all planned improvements to the other parts of the facility that previously received observations are completed well ahead of the PDUFA date,” Andersson added in the news release.

How was XS003 investigated?

One of the studies evaluating XS003 was an open-label, single-center, randomized phase 1 trial (NCT07138352) designed to investigate a single dose of XS003 under both fasting and fed conditions in healthy adult participants.4

The study included adults 18 to 55 years of age with a body mass of at least 18 mg/m2 and less than 32.0 kg/m2 who had an acceptable medical history, physical exam, ECG, and laboratory results.

Enrollees were randomly assigned to receive a single dose of XS003 at 192 mg under fasting conditions, followed by a single dose at 192 mg under fed conditions; or the inverse order.

The study’s primary end point was to evaluate pharmacokinetics of XS003 under both fasting and fed conditions. Safety was a secondary end point.

References

1. Xspray Pharma: FDA accepts New Drug Application for XS003 (nilotinib) for the treatment of CML – PDUFA date set for June 18, 2026. Xspray Pharma. News release. October 21, 2025. Accessed October 21, 2025. https://xspraypharma.com/modular_finance_pressmeddelande/xspray-pharma-fda-accepts-new-drug-application-for-xs003-nilotinib-for-the-treatment-of-cml-pdufa-date-set-for-june-18-2026/
2. Tasigna. Novartis. Updated February 2024. Accessed October 21, 2025. https://www.novartis.com/us-en/sites/novartis_us/files/tasigna.pdf
3. 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 October 21, 2025. https://azurity.com/azurity-pharmaceuticals-inc-announces-fda-approval-of-danziten-nilotinib-tablets-the-first-and-only-nilotinib-with-no-mealtime-restrictions/
4. Bioavailability study of XS003 (nilotinib) (XS003-14). ClinicalTrials.gov. Updated August 22, 2025. Accessed October 21, 2025. https://clinicaltrials.gov/study/NCT07138352