FDA releases CRL for dasatinib in chronic myelogenous leukemia/acute lymphoblastic leukemia

The U.S. Food and Drug Administration has issued a complete response letter (CRL) for dasatinib (Dasatinib) for the treatment of patients with chronic myelogenous leukemia (CML) and acute lymphoblastic leukemia (ALL).

Based on the manufacturer's observations of good manufacturing practices for the drug, the FDA elected to provide the CRL. While there were no direct observations of dasatinib production, the FDA is suspending all approvals at this facility until corrective actions are taken. An action plan to correct these observations is currently being developed. An additional meeting with the U.S. Food and Drug Administration is planned for December.

Dasatinib is designed usingXspray’s patented HyNap technology, which has proven safety and efficacy. The dose of this amorphous formulation of dasatinib is reduced by 30%. Bioequivalence allows patients to take their dosage more accurately to obtain greater benefit from treatment. Amorphous dasatinib can be used with any acid reducing agent, such as a proton pump inhibitor, H2 antagonist, or antacid.

In July 2024, dasatinib received a CRL from the U.S. Food and Drug Administration. This CRL is based on the most recent New Drug Application (NDA) submitted in February 2024. The CRL outlines the need to provide more information on third-party manufacturing facility label understanding and pre-approval inspections. The inspection took place from June 10 to 19, 2024. However, the FDA did not request additional clinical studies and did not challenge any of the submitted clinical data.

In April 2025, an updated NDA was submitted that addressed all of the FDA's previous concerns. In a press release about the resubmitted NDA, Andersson said: "The manufacturing and quality review of the new tablet batch required to resolve the FDA concerns has been carried out according to the plan of Xspray's U.S. contract manufacturer and meets all set quality requirements." He concluded: "We are fully prepared to bring dasatinib to the U.S. market upon approval later this year."

Based on dasatinib tablets (Prescribing information for Sprycel), which is currently indicated for the treatment of patients with newly diagnosed Philadelphia chromosome (Ph)-positive chronic-phase CML; chronic, accelerated, or myeloid or lymphoblastic-stage Ph-positive CML who are resistant to or intolerant to prior treatments including imatinib (Gleevec); the drug is also indicated for use in combination with chemotherapy in pediatric patients 1 year of age or older with chronic-phase Ph-positive CML and newly diagnosed Ph-positive ALL.

Prescribing information for dasatinib tablets includes warnings for myelosuppression and bleeding events, fluid retention, cardiovascular toxicity, pulmonary hypertension, serious dermatological reactions, and tumor lysis syndrome. Additionally, the most common adverse reactions associated with this drug in pediatric patients include mucositis, febrile neutropenia, pyrexia, diarrhea, nausea, vomiting, abdominal pain, cough, headache, rash, fatigue, constipation, edema, hypertension, and infection.

Reference materials:https://www.cancernetwork.com/view/fda-issues-crl-for-dasatinib-in-cml-all