FDA Accepts NDA for New Nilotinib Formulation in CML

The FDA has accepted a new drug application (NDA) for an alternative formulation of nilotinib (Tasigna) using proprietary HyNap™ technology (XS003) as a treatment for patients with chronic myeloid leukemia (CML), according to a press release from the developer, Xspray Pharma.¹

The FDA will review the NDA for the amorphous formulation of nilotinib as part of the 505(b)(2) regulatory pathway. Additionally, the regulatory agency set a Prescription Drug User Fee Act date of June 18, 2026, for this indication.

According to prior data, XS003, a potentially “improved” formulation of nilotinib, showed bioequivalence compared with the reference agent at less than half of the original dose. Additionally, the alternative formulation produced a significantly reduced food effect at 29% compared with 82% with the reference product. According to the developers, the food effect related to reference nilotinib may complicate patient adherence to treatment; those undergoing treatment with the agent are required to fast, which is noted in its boxed warning for qTC prolongation and sudden risk of death.

“The FDA’s decision to accept our NDA for review marks an important milestone,” Per Andersson, chief executive officer at Xspray Pharma, stated in the 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 tyrosine kinase inhibitors [TKIs] to the market.”

According to its prescribing information, reference nilotinib capsules received approval from the FDA in 2007 as a treatment for patients with newly diagnosed Philadelphia chromosome (Ph)–positive CML in chronic phase as well as those with chronic phase and accelerated phase Ph-positive CML who have resistance to or intolerance of prior therapy including imatinib (Gleevec).² Additionally, the FDA approved nilotinib tablets (Danziten) without mealtime restrictions for those with newly diagnosed Ph-positive CML in November 2024.³

Prescribing information for reference nilotinib includes warnings and precautions for myelosuppression, QT prolongation, sudden deaths, elevated serum lipase, liver function abnormality, electrolyte abnormalities, and hepatic impairment. The most frequent non-hematologic adverse effects (AEs) associated with the agent include rash, pruritus, headache, nausea, fatigue, myalgia, constipation, diarrhea, abdominal pain, vomiting, pyrexia, back pain, and upper urinary tract infections. Additional data from clinical trials showed the risk of AEs including benign, malignant, and unspecified neoplasms; blood and lymphatic system disorders; endocrine disorders; and immune system disorders. The agent is contraindicated in patients with hypokalemia, hypomagnesemia, and long QT syndrome.

Of note, the label for nilotinib warns that food increases the blood levels of the agent. Consequently, patients are recommended to avoid food for 2 hours before and 1 hour after a dose of nilotinib.

Developers designed XS003 an amorphous, non-crystalline formulation of the original crystalline drug.⁴ Prior findings have demonstrated a more than 50% reduced dose with XS003 compared with reference nilotinib, signifying that a lower dose of the amorphous formulation can produce similar plasma concentrations of the original drug. Developers noted a challenge associated with optimizing a lower dosage of XS003 to achieve similar bioavailability due to the reference drug’s highly variable pH-dependent solubility.

“[Because] 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…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 concluded in the press release.¹

References

1. 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 23, 2025. https://tinyurl.com/45zjp4xs
2. Tasigna® (nilotinib) Capsules. Prescribing information. FDA. 2007. Accessed October 23, 2025. https://tinyurl.com/muve6dvy
3. Azurity Pharmaceuticals, Inc. announces FDA approval of DANZITEN (nilotinib) tablets, the first and only nilotinib with no mealtime restrictions. News release. Azurity Pharmaceuticals, Inc. November 14, 2024. Accessed October 23, 2025. https://tinyurl.com/yc7ttwkf
4. Pipeline. Xspray Pharma. Accessed October 23, 2025. https://tinyurl.com/bdhkks9d