FDA Accepts NDA for New Nilotinib Formulation in Chronic Myeloid Leukemia

The US FDA has accepted the new drug application (NDA) for XS003, a formulation referencing the tyrosine kinase inhibitor (TKI) nilotinib (Tasigna), for treatment of chronic myeloid leukemia (CML).¹ With XS003’s NDA acceptance, a Prescription Drug User Fee Act (PDUFA) action date has been set for June 18, 2026.

“The FDA’s decision to accept our NDA for review marks an important milestone,” said Per Andersson, CEO of Xspray Pharma, in a press release.¹ “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.”

Standard nilotinib, an oral TKI indicated for the treatment of adult and pediatric patients with Philadelphia chromosome positive (Ph+) CML in chronic phase (CP) and accelerated phase (AP), has been FDA-approved since 2007.² However, the agent’s current prescribing information warns of risks for QT prolongation, sudden death, and other adverse events; it also advises patients to avoid food for 2 hours before and 1 hour after each dose, raising potential concerns about food interactions and safe usage that may affect patient adherence and dose adjustment.

XS003, developed with Xspray Pharma’s proprietary HyNap™ platform, demonstrates bioequivalence to its reference product when administered at less than half the dose per data from registration studies.³ Its formulation has proven beneficial in mitigating the food effect associated in standard nilotinib, amounting to a difference of 28% vs 82% with standard nilotinib.^1,3 This reduced food effect could potentially eliminate the need for fasting before administration, pending FDA review of final labeling and warnings. Further, the data show that XS003 offers improved dose linearity, allowing for better predictability in dose adjustments.

In November 2024, the FDA approved another formulation of nilotinib (Danziten) at a lower dose with no mealtime restrictions for treatment of adult patients with newly diagnosed Ph+ CP- and AP-CML that is resistant or intolerant to prior therapy that included imatinib (Gleevec).

If approved, XS003 may offer a convenient, potentially safer therapeutic option that addresses nilotinib’s current bioavailability limitations, lowering the risk of adverse effects when taken with food and thereby ameliorating treatment administration and uptake for providers and patients alike.

What studies have investigated XS003?

A phase 1, open-label, single-center, randomized crossover study (NCT07138352) was initiated by the sponsor in 2024 to evaluate the comparative oral bioavailability of XS003 under fasted vs fed conditions in 48 healthy adult patients.⁴ Here, patients were randomly assigned to receive a single 192-mg dose of XS003 under fasted or fed conditions, followed by the inverse at the same dosage.

The primary end point of the study was bioavailability, measured through pharmacokinetics. Investigators also monitored for adverse events and other safety and tolerability measures as secondary end points.

The study was completed in early 2025.

REFERENCES:

1. Xspray Pharma: FDA accepts New Drug Application for XS003 (nilotinib) for the treatment of CML – PDUFA date set for June 18, 2026. News release. Xspray Pharma. October 21, 2025. Accessed October 21, 2025. https://tinyurl.com/2pvnv4fk

2. Tasigna. Novartis. Updated February 2024. Accessed October 21, 2025. https://tinyurl.com/ypmttkf8

3. Xspray Pharma Submits XS003 to the FDA – The Company’s Second Product Candidate from the HyNap Platform. News release. Xspray Pharma. August 19, 2025. Accessed October 21, 2025. https://tinyurl.com/ts5ua3r8

4. Bioavailability Study of XS003 (Nilotinib) (XS003-14). ClinicalTrials.gov. Updated August 22, 2025. Accessed October 21, 2025. https://clinicaltrials.gov/study/NCT07138352