Can-Fite BioPharma (PETACH TIKVA, Israel), a clinical-stage drug development company focused on a portfolio of orally bioavailable, highly selective, small molecule A(3) adenosine receptor (A(3)AR) agonists with potent activities in inflammation and cancer, announced that it has initiated a phase IIb clinical study of CF101 (1-deoxy-1-[6-[[(3-iodophenyl)methyl]amino]-9H-purine-9-yl]-N-methyl-D-ribofuranuronamide), an A3AR agonist exclusively licensed from the National Institutes of Health (NIH) and Can-Fite's lead drug candidate for rheumatoid arthritis (RA). This clinical trial is expected to enroll about 250 patients in the US, Europe, and Israel, and will examine the efficacy of CF101 in combination with methotrexate (MTX) in treating RA patients.
The company also announced the receipt of the final report summarizing the results of a phase IIa clinical trial of CF101 in 74 patients with severe RA. CF101 was administered orally in three doses: 0.1 mg, 1 mg, and 4 mg over a 12-week period. The drug, given twice daily, was well tolerated without dose limiting side effects and active in reducing disease symptoms in these patients (who had failed one or more disease-modifying antirheumatic drugs or DMARDs), as measured by standard American College of Rheumatology (ACR) criteria (at 12 weeks, 55.6% and 33.3% of the patients receiving 1 mg CF101 achieved ACR 20 and 50 responses, respectively). Data from this study also suggested that A3AR levels in peripheral blood mononuclear cells may be a predictive surrogate marker of clinical response. CF101 is minimally metabolized in the liver and excreted intact in the urine.
In addition, the company will shortly begin evaluating the efficacy of this drug in the treatment of dry eye syndrome. Dry eye syndrome (keratitis sicca) is a chronic eye disease that results from inadequate tear volume, leading to eye irritation that may lead to temporary or at times permanent impairment in vision. It is a disease that is commonly found in RA patients. In January 2006, Can-Fite announced that the dry eye symptoms of several RA patients who participated in Can-Fite's phase IIa study and who also suffered from keratitis sicca were significantly improved following treatment with CF101. Dry eye syndrome is a condition affecting more than 6 million people in the US alone. Other than symptomatic treatment and the use of general immuno-suppressive drugs, there are currently no drug therapies for the treatment of this disease.
The A3AR is highly expressed in pathological inflammatory cells but has low expression levels in most normal tissue. Activation of the A3AR with agonists initiates the deregulation of the Wnt and NF-κB signal transduction pathways, resulting in a decrease in the levels of TNF-α and the induction of apoptosis of inflammatory cells.
— A. Techman