The U.S. Food and Drug Administration has issued a complete response letter (CRL) to Xspray Pharma's new drug application for Dasynoc, a novel formulation of the tyrosine kinase inhibitor dasatinib intended for treating chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL). The regulatory setback represents another hurdle in what has been a challenging approval pathway for the Swedish pharmaceutical company.
Manufacturing Issues Delay Approval
The FDA's decision was based on Good Manufacturing Practice (GMP) observations at Xspray's contract manufacturer, though the agency clarified that no observations were directed specifically at the production line used for Dasynoc. The FDA is pausing approvals of new products at the facility while corrective actions are implemented.
"It is unfortunate that manufacturing-related issues beyond our control are delaying our launch," said Per Andersson, CEO of Xspray Pharma. "We have made significant progress in the regulatory review and maintained discussions with the FDA regarding the product information for Dasynoc up to the PDUFA date."
The contract manufacturer has confirmed that a remediation plan is already in place, with a meeting scheduled with the FDA for December. Xspray plans to work closely with both the manufacturer and the FDA to expedite the resubmission process once corrective actions are completed.
Clinical Advantages of Dasynoc Formulation
Dasynoc represents a significant advancement in dasatinib formulation, demonstrating bioequivalence to the original drug at a 30% lower dose due to its improved solubility profile. This enhanced formulation addresses a critical clinical need by maintaining compatibility with proton pump inhibitors (PPIs), which are frequently co-prescribed in CML and ALL patients.
The clinical significance of this compatibility became evident in retrospective study data presented at the 2022 ASH Annual Meeting. The research showed that CML patients treated with concomitant TKIs and PPIs experienced an inferior 5-year overall survival rate of 79% compared to 94% in patients who received TKI therapy alone (HR, 3.5; 95% CI, 2.1-5.3; P < .0001). These findings indicate that PPI co-medication negatively impacts TKI absorption levels.
However, the study also demonstrated that comedication with the PPI omeprazole did not affect Dasynoc uptake in 16 healthy volunteers who participated in a crossover portion of the study, highlighting the formulation's potential clinical advantage.
Regulatory Background and Market Context
The FDA granted Dasynoc orphan drug designation in 2022 for CML treatment, a status designed to expedite development of treatments for rare diseases. This designation has facilitated ongoing communications between Xspray and the FDA throughout the regulatory process.
The current CRL follows multiple previous regulatory submissions and responses, including an April 2025 NDA re-submission. The FDA has also requested additional information demonstrating that the proposed product information is appropriate and data confirming the outcome of previously implemented corrective actions at the production line.
Current CML Treatment Landscape
TKIs serve as the cornerstone of CML treatment, with first-line options for newly diagnosed chronic-phase CML including imatinib (Gleevec), dasatinib, nilotinib (Tasigna), bosutinib (Bosulif), and asciminib (Scemblix). Treatment selection involves consideration of factors such as risk score, comorbidities, tolerability, and convenience.
Dasatinib is currently FDA-approved for multiple indications, including newly diagnosed adults with Philadelphia chromosome-positive CML in chronic phase, adults with chronic, accelerated, or blast phase Ph+ CML with resistance or intolerance to prior therapy, and pediatric patients 1 year and older with Ph+ CML in chronic phase or newly diagnosed Ph+ ALL in combination with chemotherapy.
Pipeline Progress Continues
Despite the Dasynoc setback, Xspray's other development programs continue according to plan. The company expects the FDA to initiate review of its NDA for XS003 (nilotinib) shortly, with an anticipated PDUFA date in June 2026.
