Clinical Implications Remain After Dasatinib CRL in CML/ALL

The FDA's CRL for the HyNap formulation of dasatinib due to manufacturing issues does not affect the efficacy or availability of standard dasatinib.

The oncology community has been closely tracking the development of an amorphous, lower-dose formulation of dasatinib (Dasynoc) under the HyNap technology, especially given the ongoing focus on optimizing adherence and long-term tolerability in chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL). The recent receipt of a third complete response letter (CRL) from the FDA has introduced a temporary delay for this formulation of dasatinib. A press release noted that this CRL was issued due to manufacturing-related issues, not concerns about the drug’s established clinical profile.

Of note, standard dasatinib (Sprycel) remains accessible and effective for patients. Instead, the delay only impacts the availability of the HyNap formulation for those patients who would most benefit from its potentially enhanced properties.

CancerNetwork® spoke with Yan Leyfman, MD, from NewYork-Presbyterian Hospital, over email correspondence regarding the decision and the future implications for this treatment in the leukemia space.

CancerNetwork: How does this manufacturing-related delay affect the current treatment paradigm for CML and Philadelphia chromosome–positive (Ph+) ALL?

Leyfman: The FDA’s CRL for Dasynoc [dasatinib] does not alter the established efficacy or clinical availability of dasatinib for CML and Ph+ ALL. Standard dasatinib and generics remain fully accessible and highly effective. However, patients who might have benefited from the HyNap formulation—particularly those on acid-reducing agents or who require lower doses—will need to wait until manufacturing issues are resolved. In essence, the delay affects dosing flexibility and convenience, not the therapeutic outcomes, for most patients.

What does the FDA submission under the 505(b)(2) pathway mean?

The 505(b)(2) pathway enables developers to obtain approval for new formulations of established drugs by referencing prior safety and efficacy data. For Dasynoc, Xspray Pharma leveraged this route to demonstrate bioequivalence between its amorphous, lower-dose dasatinib formulation and the reference product. This approach streamlines approval for innovations that enhance absorption or dosing convenience while still requiring full regulatory validation for quality, consistency, and manufacturing standards.

How does the HyNap formulation offer distinct clinical benefits beyond acid-reducing agent compatibility?

HyNap dasatinib’s amorphous design enhances solubility and bioavailability, minimizing variability in systemic exposure and maintaining stable drug levels, even in patients on acid-reducing therapy. Compared with conventional dasatinib, it may reduce the risk of subtherapeutic exposure and treatment resistance. The lower required dose also holds promise for fewer dose-related toxicities such as pleural effusions and cytopenias, although direct comparative safety data are still maturing.

What key efficacy and safety data support amorphous dasatinib’s profile?

Dasynoc [dasatinib] achieved bioequivalence to standard dasatinib at an approximately 30% lower dose, with comparable systemic exposure and response rates. Clinical data showed maintained efficacy even with concomitant proton pump inhibitor use—an important differentiation from traditional dasatinib. Early safety signals suggest fewer dose-related adverse events, but the overall safety profile remains consistent with dasatinib, including risks of cytopenias, bleeding, and fluid retention.

How would amorphous dasatinib measure up against existing treatment options if approved?

If approved, Dasynoc would provide a more adaptable dasatinib option—particularly beneficial for patients requiring acid suppression or reduced dosing due to comorbidities. Rather than replacing current tyrosine kinase inhibitors [TKIs] like imatinib [Gleevec], nilotinib [Tasigna], or bosutinib [Bosulif], it would complement them by addressing real-world pharmacologic and tolerability gaps. The anticipated advantages lie in dosing convenience, improved absorption, and potentially reduced toxicity without compromising efficacy.

Anything else to highlight about this space?

The TKI landscape in CML and Ph+ ALL is rapidly evolving toward precision, tolerability, and long-term disease control. Developments like Dasynoc exemplify a patient-centered shift aiming to optimize adherence, reduce interactions, and maintain durable remissions. [Although] regulatory scrutiny around manufacturing may delay availability, it ultimately reinforces the reliability and quality of next-generation therapies entering this space.

Reference

Xspray Pharma provides update on the FDA process for Dasynoc-observations at contract manufacturer delay approval. News release. Xspray Pharma. October 8, 2025. Accessed October 23, 2025. https://tinyurl.com/yc366ske