Xspray seeking FDA approval for oral CML treatment XS003
New formulation of nilotinib addresses issues related to food interactions
Xspray Pharma has submitted an application to the U.S. Food and Drug Administration (FDA) seeking approval for its oral therapy XS003 (nilotinib) for the treatment of chronic myeloid leukemia (CML), a form of blood cancer.
Developed using the company’s proprietary HyNap technology, XS003 is a next-generation formulation of nilotinib, currently sold under the brand name Tasigna, among others. The new formulation addresses issues related to food interactions and cardiac side effects of existing products.
Xspray expects the FDA to start its review within 60 days, with a decision anticipated about eight months later, according to the company.
“Patients with chronic leukemia live not only with their disease — but also with side effects from medications, often related to food interaction and concomitant treatments,” Per Andersson, CEO of Xspray, said in a company press release. “Our proprietary HyNap technology addresses these challenges and may help improve treatment outcomes and quality of life for this patient group.”
Nilotinib blocks action of key protein
Like other types of leukemia, CML is characterized by the uncontrolled growth of immature blood cells. In most cases, the cancer cells carry a genetic defect called the Philadelphia chromosome, which leads to the production of BCR-ABL, an abnormal protein that drives cancer cell growth.
Nilotinib belongs to a class of medications called tyrosine kinase inhibitors and blocks the action of BCR-ABL, leading to cancer cell death.
In its current form, however, the oral medication is hampered by variable bioavailability, or its absorption into the bloodstream, and food interactions, which increase drug exposure and raise the risk of cardiac side effects.
Xspray’s HyNap technology transformed the crystalline, or structured, form of nilotinib into an amorphous, or unstructured, form. This helps improve absorption into the bloodstream and reduce food interactions.
“Our goal is to develop and commercialize a portfolio of next-generation [protein kinase inhibitor] products with stable absorption, low variability, and minimal food interaction,” Andersson said.
XS003 achieved bioequivalence with Tasigna, developer says
The FDA granted orphan drug status to XS003 for the treatment of CML, a designation given to investigational therapies for rare diseases that comes with certain financial incentives for the company to support the therapy’s development.
The application was supported by data from clinical studies that compared the bioavailability of XS003 against Tasigna in healthy adult volunteers, under both fasting and fed conditions.
According to Xspray, XS003 achieved bioequivalence with Tasigna, meaning it reached the same level in the bloodstream, despite being administered at less than half the dose of the reference product. The therapy also showed improved dose linearity, which refers to a direct proportion between the dose of a drug and its resulting blood level.
This “may provide physicians with better predictability when adjusting doses, and thereby a greater ability to achieve improved treatment outcomes,” the company stated in its release.
Notably, the uptake of XS003 was less affected when taken with food compared with Tasigna — it increased by 28% with XS003 versus 82% with Tasigna, which “may indicate improved control and a lower risk of side effects when taken with food,” the company said.
Tasigna has a boxed warning label to ensure three hours of fasting before dosing. Because of XS003’s improved food interaction profile, Xspray said the the warning is not expected to apply to XS003.
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