Namodenoson Receives FDA Orphan Drug Designation for Pancreatic Cancer
Key Insights
Namodenoson, a drug developed by Can-Fite BioPharma, has been granted Orphan Drug Designation by the FDA for pancreatic cancer (search) treatment.
The designation offers Can-Fite potential market exclusivity for seven years post-approval, along with regulatory advantages and tax credits.
A phase 2 study is planned to assess the safety, clinical activity, and pharmacokinetics of namodenoson in patients with advanced pancreatic cancer (search).
Can-Fite BioPharma's drug candidate, Namodenoson, has received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for the treatment of pancreatic cancer (search). This designation provides Can-Fite with potential market exclusivity for seven years upon approval, along with regulatory advantages such as tax credits for clinical trials and exemption from user fees.
Clinical Trial Plans
Can-Fite is advancing its plans to initiate a phase 2 study to evaluate Namodenoson in patients with advanced pancreatic adenocarcinoma who have progressed on at least one prior line of therapy. The multicenter, open-label trial aims to enroll approximately 20 evaluable patients who will receive 25 mg of Namodenoson orally twice daily in 28-day cycles. The primary endpoint of the study is to characterize the safety profile of Namodenoson, while secondary endpoints include objective response rate, progression-free survival, disease control rate, duration of response, and overall survival.
Motti Farbstein, CEO of Can-Fite BioPharma, stated, "We are advancing our plans to start our phase 2 study in pancreatic cancer (search) and aim to commence the study by the end of year; we are thrilled that the FDA has granted orphan drug status."
Mechanism of Action and Preclinical Data
Namodenoson is an orally bioavailable drug that selectively binds to the A3 adenosine receptor (search) (A3AR), which is highly expressed on the surface of pancreatic and liver cancer cells, inducing apoptosis. A3AR has minimal expression in healthy cells, potentially leading to a favorable safety profile with minimal off-target toxicity.
Preclinical studies have demonstrated the anti-growth effect of Namodenoson on BxPC-3 pancreatic cancer (search) cells. In vitro studies showed significant dose-dependent inhibition of BxPC-3 cell growth, which was mitigated by the A3AR antagonist MRS1523. Western blot analyses revealed that Namodenoson modulates NF-κB expression and proteins in the RAS and Wnt/β-catenin signaling pathways, upregulating the apoptotic proteins Bad and Bax. In vivo studies in mice showed a significant inhibition of pancreatic cancer tumor growth with Namodenoson treatment at 10 μg/kg twice daily for 35 days, compared to control mice.
Additional preclinical research indicated that nanomolar concentrations of Namodenoson inhibited pancreatic cancer (search) growth both as a monotherapy and in combination with gemcitabine (P < .005). The combination of Namodenoson at 0.1 nM and gemcitabine at 0.2 μM had an additive inhibitory effect compared to either monotherapy (P < .001). Further western blot analyses showed that Namodenoson treatment was associated with downregulation of regulatory proteins in the Wnt pathway, including p-Akt, NF-κB, GSK-3β, and β-catenin.
Previous Clinical Trials
Namodenoson has been previously investigated in phase 2 clinical trials for liver cancer indications, including hepatocellular carcinoma (search) (HCC (search)), non-alcoholic fatty liver disease (search) (NAFLD (search)), and non-alcoholic steatohepatitis (search) (NASH (search)). A phase 3 study of Namodenoson in advanced HCC with Child-Pugh B7 cirrhosis is currently recruiting.