FDA Issues CRL to NDA for Dasynoc in CML and ALL

The FDA has issued a complete response letter (CRL) to a new drug application (NDA) for Dasynoc for the treatment of chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL), according to Xspray Pharma.¹

Dasynoc is a lower-dose, bioequivalent formulation of the tyrosine kinase inhibitor (TKI) dasatinib (Sprycel). There have been several turns along the regulatory journey for Dasynoc, including multiple CRLs and resubmissions. The latest CRL was a response to an April 2025 NDA resubmission for Dasynoc.

The FDA based its decision on Good Manufacturing Practice issues observed at Xspray’s contract manufacturer. Xspray reported that a plan to rectify these issues has been launched by the manufacturer. Xspray is scheduled to meet with the FDA in December.

“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 Dasynoc up to the PDUFA date,” Per Andersson, CEO of Xspray Pharma, stated in a press release. “We will now work closely with both the manufacturer and the FDA to expedite the process and enable a resubmission as soon as the corrective actions have been completed.”¹

The FDA granted Dasynoc an orphan drug designation in 2022 for the treatment of patients with CML.² The designation, which is designed to expedite the development of new treatments for rare diseases, is what has given Xspray a channel to have these open communications with the FDA throughout this regulatory process.

What Clinical Evidence Supports Dasynoc in CML?

Xspray previously reported that Dasynoc has demonstrated bioequivalence to dasatinib at a 30% lower dose because the novel formulation has a better solubility profile. Data have also shown that Dasynoc is compatible with proton pump inhibitors (PPIs), which physicians often coprescribe in patients with CML and ALL.

Retrospective study data shared at the 2022 ASH Annual Meeting showed that patients with CML who were treated with concomitant TKIs and PPIs experienced an inferior 5-year overall survival rate compared with the rate in patients who received a TKI alone at 79% vs 94%, respectively (HR, 3.5; 95% CI, 2.1-5.3; P < .0001).³ These findings indicate absorption levels of TKIs are negatively impacted by PPIs. However, the research also showed that comedication with the PPI omeprazole did not affect Dasynoc uptake in 16 healthy volunteers who participated in a crossover portion of the study.

What Are the FDA-Approved Indications for Dasatinib?

Dasatinib is currently approved by the FDA for:

• Newly diagnosed adults with Philadelphia chromosome-positive (Ph+) CML in chronic phase.
• Adults with chronic, accelerated, or myeloid or lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy, including imatinib.
• Adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy.
• Pediatric patients 1 year of age and older with Ph+ CML in chronic phase.
• Pediatric patients 1 year of age and older with newly diagnosed Ph+ ALL in combination with chemotherapy.⁴

REFERENCES:

1. Xspray Pharma provides update on the FDA process for Dasynoc – observations at contract manufacturer delay approval. Posted online and accessed October 8, 2025. https://tinyurl.com/mvmw9nv5

2. Dasynoc granted Orphan Drug Designation in the US for the treatment of chronic myeloid leukemia. Posted online June 17, 2022. Accessed October 8, 2025. https://tinyurl.com/5yxmp4yk

3. 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

4. FDA prescribing label: Sprycel. Last revised July 2024. Accessed October 8, 2025. https://tinyurl.com/4k4zarzf