Xspray Pharma’s product portfolio is continuously evolving and, to date, has three announced product candidates based on the company’s HyNap platform: XS004 dasatinib, XS003 nilotinib and XS008 axitinib. These are improved, amorphous versions of established and marketed protein kinase inhibitors with orphan drug status. The original drugs have secondary patents expiring between 2026 and 2032 and their total annual sales for 2022 exceeded USD 3.4 billion in the US market and USD 5.1 billion globally.
New projects will focus on the same indications as XS004 dasatinib and XS003 nilotinib as well as on other cancer indications. The development processes created with XS004 dasatinib and XS003 nilotinib will be applicable to the new projects allowing to significantly reduce development timelines.
Xspray Pharma has developed an improved version of dasatinib, XS004 dasatinib, for the treatment of chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL). XS004 dasatinib has achieved bioequivalence with a 30 percent lower dose compared to the original drug, Sprycel®. The study confirms that XS004 dasatinib:
• is unaffected by the pH value of the stomach and can thus be used together with omeprazole without affecting the absorption of dasatinib, which facilitates treatment of peptic ulcers while the patient is being treated for cancer
• yields a more even and consistent uptake of dasatinib in the body without those cases of low uptake that are linked to the reference product
• can be administered at a lower dosage than the reference product, which is expected to yield fewer side effects
The market value for XS004 dasatinib is high both during and after the end of the patent window. An application for US market approval for XS004 dasatinib was submitted to FDA under the 505(b)(2) NDA regulatory procedure, November 2021.
The primary patent for the original drug expired in December 2020 and the secondary patent expires in 2026, which could give XS004 dasatinib a favorable market establishment with limited competition. In 2022, the global market for Sprycel® amounted to approximately USD 2.2 billion, of which the US market accounted for approximately USD 1.5 billion.
Xspray Pharma is developing XS003 nilotinib as an improved version of Tasigna® (nilotinib) for the treatment of chronic myeloid leukemia (CML). Global sales of Tasigna® totaled USD 1,9 billion in 2022, of which the US market accounted for USD 0.9 billion.
Tasignas drug substance patent expires in January 2024, and the secondary patent in October 2032. Xspray Pharma has conducted a clinical trial that investigated the pharmacokinetic properties, and food interaction effects of a XS003 nilotinib prototype. The study showed that XS003 nilotinib significantly reduces food interaction compared with Tasigna® after a high-fat meal. Studies have also shown significantly higher bioavailability of XS003 nilotinib compared with Tasigna®. Development is progressing, with the target of conducting bioavailability studies that, in the event of positive findings, will form the basis of the application for market approval under the 505(b)(2) NDA procedure.
The US Food and Drug Administration has granted orphan drug status to XS003 nilotinib for the treatment of chronic myeloid leukemia (CML), in view of the fact that XS003 nilotinib addresses the food interaction that is included in the warning text for Tasigna® in the US.
The development of the commercial formulation is complete, as well as manufacturing of clinical trial materials. Pivotal clinical studies are in progress and the company expects to complete these by 2023.
The product candidate is based on the original substance axitinib which is used for treatment of kidney cancer. The PKI market for kidney cancer had sales of approximately USD 3 billion in the US in 2022. The currently marketed product which is based on axitinib is Inlyta® and its patent expiry creates an attractive launch window between April 2025 and December 2030 in the US. Sales of Inlyta amounted to USD 0.6 billion in the US and USD 1.0 billion globally in 2022.