FDA Again Rejects Reformulated Dasatinib for CML and ALL Treatment

The FDA has issued a complete response letter (CRL) for dasatinib (Dasynoc), a lower-dose, bioequivalent formulation of the tyrosine kinase inhibitor (TKI) dasatinib (Sprycel), for the treatment of chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL).¹

The letter cited unresolved manufacturing concerns at the sponsor’s third-party production partner, NerPharMa, rather than issues with clinical data. The regulatory agency requested additional commercial-scale batch data, building on prior corrective actions the company had already taken.

The rejection follows a resubmitted new drug application (NDA) that the FDA accepted for review under the 505(b)(2) pathway in March 2026.² It marks the third CRL for the agent after multiple NDA resubmissions: the FDA previously issued a CRL in October 2025 over Good Manufacturing Practice (GMP) findings at the same contract manufacturer, and issued an earlier CRL in 2024 tied to labeling and dosing clarity. The manufacturer has reportedly completed remediation at its site and notified the FDA of its progress, though the agency has not yet determined whether a reinspection is required to finalize its assessment of the facility.

“The CRL confirms that the remaining uncertainty is now linked to NerPharMa sufficiently addressing the FDA’s observations at their manufacturing site and batch data from consecutive manufacturing runs being provided. As expected, this will require a NDA resubmission,” Blake Leitch, CEO of Xspray Pharma, stated in a news release.¹ The company has stated it aims to resubmit another NDA as soon as possible in 2026.

Formulation and Supporting Data

The dasatinib reformulation was developed on Xspray's proprietary HyNap platform, which is designed to produce amorphous, more soluble formulations of marketed protein kinase inhibitors. The sponsor has reported that the reformulation is bioequivalent to standard dasatinib at a 30% lower dose, owing to an improved solubility profile, and that its absorption is less dependent on gastric pH than the reference product.

This distinction is clinically relevant given how often TKIs and proton pump inhibitors (PPIs) are co-prescribed in this population. Retrospective data presented at the 2022 ASH Annual Meeting showed that patients with CML who received a TKI concomitantly with a PPI had a lower 5-year overall survival rate than those on a TKI alone (79% vs 94%, respectively; HR, 3.5; 95% CI, 2.1-5.3; P <.0001), consistent with reduced TKI absorption at elevated gastric pH.³ In a crossover portion of that research involving 16 healthy volunteers, coadministration of the PPI omeprazole did not affect uptake of the reformulation.

Current Treatment Landscape

TKIs remain the backbone of CML management. First-line options for newly diagnosed chronic-phase disease include imatinib (Gleevec), dasatinib, nilotinib (Tasigna), bosutinib (Bosulif), and asciminib (Scemblix), with selection guided by risk score, comorbidities, tolerability, and convenience.

Dasatinib is FDA approved 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 Ph+ ALL with resistance or intolerance to prior therapy; pediatric patients 1 year and older with Ph+ CML in chronic phase; and pediatric patients 1 year and older with newly diagnosed Ph+ ALL in combination with chemotherapy.

REFERENCES

1. Xspray Pharma receives Complete Response Letter (CRL) from FDA for Dasynoc. News release. Xspray Pharma. August 19, 2026. Accessed August 26, 2026. https://tinyurl.com/2kcejwv7

2. Xspray Pharma: FDA accepts resubmitted application for market approval of Dasynoc® – PDUFA date August 25, 2026. News release. Xspray Pharma. March 11, 2026. Accessed May 15, 2026. https://tinyurl.com/yvr82rjm

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