FDA Issues CRL for Dasatinib in Chronic Myeloid Leukemia

The FDA has issued a complete response letter (CRL) to the new drug application (NDA) seeking approval of dasatinib (Dasynoc), a next-generation formulation of the protein kinase inhibitor, for the treatment of patients with chronic myeloid leukemia (CML).1

The FDA’s decision is based on Good Manufacturing Practice observations at the company’s contract manufacturing facility. Although no observations were directed at the production line used for dasatinib, the FDA is pausing approvals of new products at the site during the implementation of corrective actions.

According to the manufacturer, a remediation plan has already been initiated, and a meeting with the FDA is scheduled for December 2025 to address the outstanding issues. The NDA for dasatinib sought approval for a formulation designed to maintain efficacy at lower doses, reduce pharmacokinetic variability, and mitigate drug-drug interactions commonly associated with acid-suppressive agents.

“It is unfortunate that manufacturing-related issues beyond our control are delaying our launch. We have made significant progress in the regulatory review and maintained discussions with the FDA regarding the product information for [dasatinib] up to the [Prescription Drug User Fee Act target action] date,” Per Andersson, chief executive officer of Xspray Pharma, said in a news release. “We will now work closely with both the manufacturer and the FDA to expedite the process and enable a resubmission [of the NDA] as soon as the corrective actions have been completed.”

What is the Mechanism of Action of Dasatinib?

Dasantinib is known to exhibit pH-dependent solubility, with elevated gastric pH significantly reducing plasma drug concentrations.2 Co-administration of dasatinib with proton pump inhibitors decreases systemic exposure by more than 40%, prompting cautionary guidance from the FDA. Dasatinib was designed to improve the solubility of the active compound at slightly acidic and neutral pH levels, reducing its dependency on gastric acidity for absorption. This property allows for stable pharmacokinetics even when taken alongside proton pump inhibitors, such as omeprazole.

What clinical and regulatory activity has dasatinib garnered so far?

Evidence from a retrospective registry presented at the 2022 ASH Annual Meeting, demonstrated that patients with CML receiving concomitant treatment with TKIs and proton pump inhibitors (n = 302) had an inferior 5-year overall survival rate of 79% compared with 94% in patients treated with TKIs alone (n = 374; HR, 3.5; 95% CI, 2.1-5.3; P < .0001). These results underscored the detrimental effect of reduced TKI absorption secondary to proton pump inhibitor co-administration.

Dasatinib previously received orphan drug designation from the FDA in 2022 for the treatment of patients with CML, reflecting the FDA's recognition of its therapeutic relevance in this patient population.3 On February 13, 2024, the FDA accepted the resubmitted NDA for dasatinib for the treatment of patients with CML.4

The original NDA for dasatinib was submitted in 2021 under the 505(b)(2) regulatory pathway, which is used for modified or improved versions of approved drugs.5 The FDA initiated a full review of the application in early 2022. However, in July 2023, the FDA issued a CRL to the manufacturer requesting additional information regarding optimal dosing parameters and details related to a third-party manufacturing facility.6

The CRL applied to all 6 proposed dosage strengths of dasatinib (15 mg, 36 mg, 50 mg, 57 mg, 70 mg, and 100 mg) but did not cite any deficiencies in the product’s stability or the clinical data supporting its efficacy and safety. Instead, the FDA sought further clarification to ensure consistency in dosing and manufacturing processes. Following the receipt of the CRL, Xspray Pharma worked to address the FDA’s requests and resubmitted the NDA with the required information.

References

1. Xspray Pharma provides update on the FDA process for Dasynoc – observations at contract manufacturer delay approval. Xspray Pharma. News Release. October 8, 2025. Accessed October 8, 2025. https://xspraypharma.com/modular_finance_pressmeddelande/xspray-pharma-provides-update-on-the-fda-process-for-dasynoc-observations-at-contract-manufacturer-delay-approval/
2. Larfors G, Lennernäs H, Liljebris C, et al. Comedication of proton pump inhibitors and dasatinib is common in CML but XS004, a novel amorphous solid dispersion formulation of dasatinib, provides improved uptake and low pH-dependency, minimizing unwanted drug-drug interactions. Blood. 2022;149(suppl 1):6769-6770. doi:10.1182/blood-2022-156487
3. Dasynoc granted orphan drug designation in the US for the treatment of chronic myeloid leukemia. News release. Xspray Pharma AB. June 17, 2022. Accessed October 7, 2025. https://xspraypharma.com/modular_finance_pressmeddelande/dasynoc-granted-orphan-drug-designation-in-the-us-for-the-treatment-of-chronic-myeloid-leukemia/
4. FDA Accepts Xspray Pharma’s NDA resubmission for Dasynoc – PDUFA date set to 31 July 2024. News Release. Xspray Pharma AB. February 12, 2024. Accessed October 7, 2025. https://www.biospace.com/article/releases/fda-accepts-xspray-pharma-s-nda-resubmission-for-dasynoc-pdufa-date-set-to-31-july-2024/?keywords=cancer/
5. About us – a timeline. Xspray Pharma. Accessed February 13, 2024. https://xspraypharma.com/about-us/2313-2/
6. Xspray Pharma receives request for additional information concerning Dasynoc from FDA. News Release. Xspray Pharma AB. July 11, 2023. Accessed October 7, 2025. https://xspraypharma.com/modular_finance_pressmeddelande/xspray-pharma-receives-request-for-additional-information-concerning-dasynoc-from-fda/