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Established treatments for advanced hepatocellular carcinoma (HCC) with Child-Pugh cirrhosis B (CPB, moderate hepatic dysfunction) are lacking. A recently published randomized phase 2 study in CPB HCC investigating the safety and efficacy of namodenoson (25 mg BID), an A3 adenosine-receptor agonist vs. placebo, suggested a favorable safety profile and a positive efficacy signal in patients with HCC with a CPB score of 7 (CPB7). The present study reports a 61-year-old woman with CPB7 HCC who received namodenoson for over 6 years through this study and its open-label extension. Computed tomography scans demonstrated partial and complete responses after 7 weeks and 4 years of treatment, respectively. Low albumin levels (31 g/l) and elevated baseline levels of alanine transaminase and aspartate aminotransferase (68 U/l and 44 U/l, respectively) were reported. After 4 weeks of treatment, these levels normalized and were stable for over 6 years. No treatment-emergent adverse events were noted. At the time of reporting, the response is ongoing as manifested by imaging studies and liver function evaluation.

Namodenoson, an A3 adenosine-receptor agonist, showed promising results in advanced hepatocellular carcinoma (HCC) and moderate hepatic dysfunction (Child–Pugh B; CPB) in a phase I/II clinical study. This phase II study investigated namodenoson as second-line therapy in such patients. Patients were randomized 2:1 to twice a day (BID) namodenoson (25 mg; n = 50) or placebo (n = 28). The primary endpoint (overall survival [OS]) was not met. Median OS was 4.1/4.3 months for namodenoson/placebo (hazard ratio [HR], 0.82; 95% confidence interval [CI] 0.49–1.38; p = 0.46). Pre-planned subgroup analysis of CPB7 patients (34 namodenoson-treated, 22 placebo-treated) showed a nonsignificant improvement in OS/progression-free survival (PFS). OS: 6.9 versus 4.3 months; HR, 0.81; 95% CI: 0.45–1.43, p = 0.46. PFS: 3.5 versus 1.9 months; HR, 0.89; 95% CI: 0.51–1.55, p = 0.67 (log-rank test). The difference in 12-month OS was significant (44% versus 18%, p = 0.028). Response rates were determined in patients for whom ≥ 1 assessment post-baseline was available (34 namodenoson-treated, 21 placebo-treated). Partial response was achieved by 3/34 (8.8%) and 0/21 (0%) patients, respectively. Namodenoson was well-tolerated, with a safety profile comparable to that of the placebo group. No treatment-related deaths were reported; no patients withdrew due to toxicity. In conclusion, namodenoson demonstrated a favorable safety profile and a preliminary efficacy signal in HCC CPB.

CF101, an orally bioavailable A3 adenosine receptor (A3AR) agonist, demonstrated very good safety and anti-inflammatory effect in Phase II clinical studies in patients with rheumatoid arthritis (RA) and psoriasis. A3AR expression level in peripheral blood mononuclear cells has been defined as a biological predictive marker, based on a significant correlation found in a former RA Phase II study between its over expression at baseline and positive patients' response to CF101 treatment. 79 patients were enrolled to a phase II, multicenter, randomized, double-blind, Placebo controlled, parallel-group study designed to assess the efficacy and safety of CF101 1mg vs. placebo, administered orally twice daily to patients with active RA for 12 weeks. Primary efficacy endpoint was ACR20 response at week 12 and secondary efficacy included ACR 50/70. Patients were enrolled based on A3AR mRNA expression level, utilized as an inclusion criterion. (NCT # NCT01034306) CF101 was found to be safe and well tolerated. CF101 achieved ACR20 of 48.6%, statistically significantly higher than that of the placebo group (25.0%) at week 12 (P=0.0352). CF101 showed superiority in ACR50 and ACR70 values vs. placebo. Interestingly, ACR20, ACR50 and ACR70 response rate at week 12 in a subpopulation with no prior systemic therapy was impressively higher (ACR20 75%) compared to the response of the whole patient population treated with CF101. CF101 reached the primary endpoint in the current study demonstrating clear evidence of efficacy and safety when given orally as monotherapy for 12 weeks in patients with active RA.