Cabozantinib (s)-Malate

Less than a year after the FDA turned down the resubmitted application for the company’s leukemia prospect Dasynoc, Xspray Pharma has again hit a wall at the U.S. regulator. This week, the FDA handed Xspray another Complete Response Letter on Dasynoc, an “optimized” version of Bristol Myers Squibb’s cancer treatment Sprycel (dasatinib) in development to tackle chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL). The letter addressed “previously communicated” manufacturing observations at Xspray’s third-party production partner, NerPharMa, and posed a request for additional commercial-scale batch data, which itself follows previous corrective actions, the company said in an Aug. 19 release. NerPharMa, based in Italy, has already wrapped up remediation efforts at its site and alerted the FDA of its progress, per Xspray, which acknowledged that the U.S. regulator “has yet to determine if a reinspection is required for the agency to finalize its assessment of the facility’s status.” When the FDA rebuffed Dasynoc last October, it similarly flagged concerns with Xspray’s manufacturing partner, with the company’s then-CEO Per Andersson reflecting that it was “unfortunate that manufacturing-related issues beyond our control are delaying our launch.” With the latest decision, Xspray says it now plans to resubmit its Dasynoc application as soon as possible, before the end of the year. To meet the FDA’s requests, Xspray noted that it will prioritize production of additional commercial-scale Dasynoc batches—already sewn into its launch strategy—to provide the production data the agency requires. As with the prior rejection, Xspray stressed that the FDA raised no questions around its drug candidate’s clinical data, bioequivalence or stability. The company also stressed that a risk of medication error raised in past rejections “has been resolved.” “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,” Xspray CEO Blake Leitch said in a statement. “As expected, this will require an NDA resubmission.” In the meantime, the company says it will continue to prep for a Dasynoc launch in the U.S., with the hopes that once an approval comes through, the product can reach patients as quickly as possible. Back in February, Sweden-headquartered Xspray announced Leitch’s appointment as the company’s new chief executive, with prior helmsman Andersson transitioning into the role of chief scientific officer. The changes were designed to help with Xspray’s ongoing efforts to evolve into a commercial-stage pharmaceutical company. Xspray, which has yet to secure an FDA approval for Dasynoc or any other asset, leverages a unique business model hinging on its HyNap platform, which the company uses to design “improved versions” of cancer-fighting protein kinase inhibitor (PKI) drugs. Apart from the Sprycel-based Dasynoc, Xspray’s other lead candidate Nilopki—an optimized version of Novartis’ Tasigna—is also under FDA review. The company is also working on so-called optimized versions of Pfizer’s Inlyta and Exelixis’ Cabometyx. Prior to this week, last year’s CRL was not the first Dasynoc received. The company’s first approval effort for the drug was met with a rejection in 2023, with the FDA at the time specifically asking for clarifying information around dosing that would help patients avoid confusion. Another CRL around label comprehension and contract manufacturer concerns surfaced in 2024, but Xspray reiterated Wednesday that it has since resolved those medication error issues. The company’s stock took a sizeable hit this week on news of the latest FDA rebuff.

Ipsen’s cabozantinib has been accepted by the Scottish Medicines Consortium (SMC) for restricted use within NHS Scotland to treat adults with advanced neuroendocrine tumours (NETs). NETs are rare, with a prevalence of seven per 100,000 people in Scotland. They typically develop slowly, and people living with NETs may require multiple lines of therapy as the disease progresses. Treatment options following progression are often limited and can vary depending on the primary tumour site and other factors, making it challenging to define the optimal sequencing of treatments. “Neuroendocrine cancers can have a profound impact on people affected by the disease and those closest to them,” commented Lisa Walker, CEO of Neuroendocrine Cancer UK. “Neuroendocrine tumours, a type of neuroendocrine cancer, often grow at a different and frequently slower rate than many other cancers, including neuroendocrine carcinomas. As a result, symptoms may not appear in the earliest stages or may be mistaken for those of more common conditions, meaning diagnosis is often delayed until the disease is more advanced.” The treatment is for adults with unresectable or metastatic, well-differentiated extra-pancreatic (epNET) and pancreatic (pNET) neuroendocrine tumours who have progressed following at least one prior systemic therapy other than somatostatin analogues. The SMC decision was based on data from the phase 3 CABINET trial that investigated cabozantinib versus placebo in people living with advanced pNETS and epNETs who have progressed following at least one prior systemic therapy other than somatostatin analogues. The trial demonstrated a 77% and 62% reduction in the risk of disease progression or death versus placebo for pNETs and epNETs, respectively. “This recommendation by the SMC is a positive and welcome development for people living with advanced neuroendocrine tumours in Scotland,” commented Professor Nicholas Reed, Consultant Clinical Oncologist at the Beatson Oncology Centre, Glasgow. “As an oral treatment, this may also reduce the need for patients to spend time in hospital.” Cabozantinib is currently undergoing review by the National Institute for Health and Care Excellence (NICE) in this indication.