Cardiovascular disease is the main cause of early death in CKD and type 2 diabetes mellitus, and is caused by an imbalance between promoters and inhibitors of mineralization, which leads to vascular calcification.
The study, “Alkaline phosphatase: a novel treatment target for cardiovascular disease in CKD,” appeared in the journal Nature Reviews Nephrology. It describes the mechanisms that link alkaline phosphatase (ALP) to vascular calcification, inflammation and cardiovascular disease.
Apabetalone, also known as RVX-208, is a selective inhibitor of the BET family of proteins that regulate mechanisms responsible for turning genes on and off. Because of the proteins’ important regulatory role, inhibiting them can help people with CKD, diabetes, heart disease, Alzheimer’s and other conditions.
In May, the U.S. Food and Drug Administration (FDA) approved the design of a Phase 2a clinical trial of apabetalone for CKD patients on dialysis. The trial (NCT03160430) will test apabetalone’s safety and its ability to treat CKD in combination with standard of care therapies.
Part A of the study is an open-label, single-dose evaluation of 100 mg apabetalone in eight patients with CKD who receive hemodialysis as standard of care. Part B is a double-blind, placebo-controlled study that will compare the efficacy of a combo therapy that includes apabetalone with that of a placebo. Its aim is to see if apabetalone, in combination with standard of care, can lower biomarkers of kidney disease better than standard of care alone.
Calgary-based Resverlogix also announced that Pfizer has applied for a patent to protect its use of BET-family bromodomain inhibitors to increase frataxin in patients with Friedreich’s ataxia. RVX-208 was listed as a potentially effective agent against this disease.
“We welcome the attention drawn to Resverlogix and apabetalone from significant industry groups such as Nature Reviews Nephrology and Pfizer,” Resverlogix President and CEO Donald McCaffrey said in a press release. “Due to the dramatic growth of BET Bromodomain publications over the past decade, it is not surprising that our advanced Phase 3 compound, apabetalone, is now drawing expanded attention from the global academic and pharmaceutical communities.”