FDA Issues Complete Response Letter for Xspray’s Nilopki NDA

Xspray Pharma has received a Complete Response Letter (CRL) from the U.S. Food and Drug Administration (FDA) for its New Drug Application (NDA) seeking approval of Nilopki™, an optimized formulation of nilotinib for chronic myeloid leukemia (CML). The agency stated it cannot approve the application in its current form, citing deficiencies in dose mapping, manufacturing validation, and facility inspection requirements. No new clinical efficacy or safety studies were requested.

Scientific and Clinical Context

Nilopki is an improved formulation of nilotinib, the active ingredient in Novartis’ Tasigna®, developed using Xspray’s proprietary HyNap™ technology platform. HyNap produces amorphous solid dispersions that improve drug absorption and pharmacokinetic performance.

Nilotinib is a second-generation BCR-ABL tyrosine kinase inhibitor widely used to treat chronic myeloid leukemia. However, standard nilotinib therapy requires strict fasting before and after dosing, posing adherence challenges that impact long-term treatment outcomes.

Nilopki demonstrated comparable bioavailability to Tasigna while delivering a 52% lower dose and eliminating fasting requirements. These improvements could simplify treatment administration and support better adherence among patients with CML.

Regulatory Review Details

The FDA outlined three key issues in the CRL:

• Dose Mapping: Regulators requested a one-to-one dose mapping between Tasigna and Nilopki, beginning with a Nilopki dose that produces exposure comparable to Tasigna 200 mg.
• Manufacturing Validation: Additional evidence is required to demonstrate commercial manufacturing capability for nilotinib amorphous solid dispersion batches.
• Facility Inspection: The FDA reiterated concerns related to Xspray’s third-party manufacturing partner, noting that satisfactory responses to inspection findings are required and that a pre-approval inspection may still be necessary.

Nilopki was filed under the 505(b)(2) pathway, which allows reliance on existing data for previously approved drugs while requiring bridging evidence for formulation changes.

Xspray said it will carefully review the CRL, seek clarification where needed, and work with regulators and industry experts to determine the most efficient path toward resubmission.

Xspray Evaluates FDA Feedback and Resubmission Pathway

Chief Executive Officer Blake Leitch expressed disappointment with the outcome given the advanced stage of labeling discussions with the FDA earlier this year. He emphasized that the deficiencies are product-specific and that the company intends to work closely with regulators and partners to resolve the remaining questions.

Leitch acknowledged that a U.S. launch in 2026 is now unlikely, with approval potentially shifting into 2027 depending on resubmission and review timelines. He also reaffirmed confidence in Nilopki’s clinical profile and the long-term potential of the company’s HyNap-based pipeline.

Regulatory Delay Shifts Focus to Pipeline and Next Steps

If approved, Nilopki could offer a differentiated treatment option in CML by removing fasting restrictions while maintaining comparable systemic exposure at a lower dose. The product represents a key commercial opportunity within the established BCR-ABL inhibitor market.

Xspray’s broader strategy remains unchanged despite the regulatory setback. The company continues to advance a portfolio of HyNap-based product candidates targeting established protein kinase inhibitors.

Its second HyNap-based candidate, Dasynoc®, is currently under FDA review, with a Prescription Drug User Fee Act (PDUFA) decision date set for August 25, 2026. Xspray said it will provide further updates on Nilopki’s regulatory pathway once discussions with the FDA are complete and next steps have been finalized.

Reference

Xspray Pharma Receives CRL from U.S. FDA for Nilopki™ – Xspray