The Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to apabetalone (Resverlogix Corp) in combination with standard of care therapy, including high-intensity statins, for the secondary prevention of major adverse cardiac events (MACE) in patients with type 2 diabetes mellitus and recent acute coronary syndrome.
Apabetalone is a first-in-class, small molecule, bromodomain and extraterminal domain (BET) inhibitor that selectively targets bromodomain 2 (BD2) at the transcription level. The investigational drug is believed to normalize dysregulated epigenetics of chronic diseases through selective BD2 inhibition. BET proteins are epigenetic readers that contribute to a variety of diseases by increasing production of dysregulated proteins.
The designation is supported by data from the phase 3 BETonMACE trial that evaluated the efficacy and safety of apabetalone in the prevention of MACE in high-risk type 2 diabetes patients with coronary artery disease (N=2425). Patients were randomized to receive either apabetalone 100mg twice daily or placebo, with standard of care therapy (high-intensity statin) for 120 weeks. The primary end point was the reduction in narrowly defined MACE, defined as a single composite end point of cardiovascular (CV) death, nonfatal myocardial infarction or stroke.
Results demonstrated that apabetalone did not meet the study’s primary end point (hazard ratio [HR] 0.82 [95% CI, 0.65-1.04]; P =.11). However, apabetalone did achieve key secondary end points showing significant reductions in hospitalizations due to congestive heart failure vs placebo (HR 0.59 [95% CI, 0.38-0.94]), along with CV improvements in 2 prespecified subpopulations, including patients with chronic kidney disease. Moreover, patients with moderate to severe cognitive decline reported significant improvements in cognition when treated with apabetalone, as measured by Montreal Cognitive Assessment (MoCA).
“This important designation – the first for a major cardiovascular indication – entails working closely with the FDA to facilitate a time-efficient drug development program including planned clinical trials and plans for expediting the manufacturing development strategy for apabetalone,” said Donald McCaffrey, President and CEO.
The Company is also assessing the effects of apabetalone in patients with pulmonary arterial hypertension (early phase 1), end-stage renal disease treated with hemodialysis (phase 1/2), and Fabry disease (phase 1/2).
For more information visit resverlogix.com.