FDA Grants Orphan Drug Designation to Namodenoson for Pancreatic Cancer

The FDA has granted orphan drug designation to namodenoson for the treatment of patients with pancreatic cancer.¹

Namodenoson is a small, orally bioavailable drug that binds with high affinity to and is highly selective for the A3 adenosine receptor (A3AR) on the surface of pancreatic cancer and liver cancer cells, inducing apoptosis of these cancer cells. A3AR is highly expressed on cancer cells but has low expression on normal cells, which accounts for the tolerable safety profile of namodenoson.

A multicenter, open-label, phase 2 study evaluating namodenoson in patients with pancreatic cancer is in preparation. The trial will enroll approximately 20 patients with advanced disease who have progressed on at least 1 line of therapy. The primary objective of the trial is to characterize the safety profile of namodenoson. A key secondary objective is to investigate the clinical activity of the agent, as determined by end points including objective response rate per RECIST 1.1 criteria, progression-free survival, disease control rate, duration of response, and overall survival. The pharmacokinetics of namodenoson will also be evaluated. All patients will receive namodenoson at 25 mg twice daily in consecutive 28-day cycles, and patients will be regularly monitored for safety.

“We are advancing our plans to start our phase 2 study in pancreatic cancer and aim to commence the study by the end of the year; we are thrilled that the FDA has granted orphan drug status [to namodenoson],” Motti Farbstein, chief executive officer of Can-Fite BioPharma, the developer of Namodenoson, stated in a news release.

A preclinical study investigating the anti-growth effect of namodenoson on BxPC-3 pancreatic cancer cells that were cultured in the agent at doses ranging from 5 nM to 20 nM for 24 hours at 37° Cshowed that the agent was associated with significant dose-dependent inhibition of BxPC-3 cell growth, which was mitigated by the A3AR antagonist MRS1523.² Additionally, western blot analyses performed on BxPC-3 cells cultured at 20 nM for 24 hours at 37° C demonstrated that namodenoson modulated NF-κB expression, as well as proteins in the RAS and Wnt/β-catenin signaling pathways, facilitating the upregulation of the apoptotic proteins Bad and Bax. In vivo studies of BxPC-3 cells in mice showed a significant inhibition of pancreatic cancer tumor growth in mice that received namodenoson at 10 μg/kg twice daily for 35 days compared with control mice. The study authors concluded that these findings supported the continued evaluation of namodenoson in pancreatic cancer.

Another preclinical study cultured BxPC-3 human pancreatic cancer cells in the presence and absence of namodenoson doses of 0.01 nM, 0.1 nM, and 1 nM.³ Findings from 3[H]-thymidine proliferation assays showed that namodenoson treatment resulted in significant dose-dependent inhibition of BcPC-3 cells compared with the absence of namodenoson (P < .005). Moreover, the combination of namodenoson at 0.1 nM and gemcitabine at 0.2 μM was shown to have an additive inhibitory effect compared with namodenoson monotherapy and gemcitabine monotherapy (P < .001). Furthermore, western blot analyses demonstrated that treatment with namodenoson was associated with downregulation of regulatory proteins in the Wnt pathway, including p-Akt, NF-κB, GSK-3β, and β-catenin. The study authors concluded that nanomolar concentrations of namodenoson inhibited pancreatic cancer growth both as a monotherapy and in combination with gemcitabine.

Namodenoson has been previously evaluated in phase 2 clinical trials (NCT02128958; NCT00790218) for 2 liver cancer indications, as well as in the second-line hepatocellular carcinoma setting (NCT05201404), as a therapy for patients with non-alcoholic fatty liver disease (NCT02927314), and for those with non-alcoholic steatohepatitis (NCT04697810).¹

References

1. FDA grants orphan drug designation to Can-Fite’s Namodenoson for pancreatic cancer. News release. Can-Fite BioPharma. October 9, 2024. Accessed October 9, 2024. https://ir.canfite.com/news-events/press-releases/detail/1068/fda-grants-orphan-drug-designation-to-can-fites
2. Itzhak I, Bareket-Samish A, Fishman P. Namodenoson inhibits the growth of pancreatic carcinoma via deregulation of the Wnt/β-catenin, NF-κB, and RAS signaling pathways. Biomolecules. 2023;13(11):1584. doi:10.3390/biom13111584
3. Fishman P, Bareket-Samish A, Itzhak I. Effects of namodenoson on pancreatic carcinoma: preclinical evidence. J Clin Oncol. 2023;41(suppl 16). doi:10.1200/JCO.2023.41.16_suppl.e15134