"Indirect HDL-based therapeutics include the apoA-I transcription up-regulator RVX-208, the lecithin-cholesterol acyltransferase (LCAT) recombinant protein ACP-501, niacin, and CETP inhibitors (Table 1). RVX-208 lacked efficacy against atherosclerosis and caused a dose-dependent increase in liver transaminase levels [134,135]."

Reference 134 is the ASSERT trial publication: Nicholls SJ, Gordon A, Johansson J, et al. Efficacy and safety of a novel oral inducer of apolipoprotein a-I synthesis in statin-treated patients with stable coronary artery disease a randomized controlled trial. J Am Coll Cardiol 2011; 57:1111–1119.

Reference 135 is the ASSURE trial publication: Nicholls SJ, Puri R, Wolski K, et al. Effect of the BET protein inhibitor, RVX-208, on progression of coronary atherosclerosis: results of the phase 2b, randomized, double-blind, multicenter, ASSURE trial. Am J Cardiovasc Drugs 2016; 16:55–65.

It is true that in ASSERT there was a dose dependent increase in liver transaminase levels. However, it fails to point out the transient nature of the liver transaminase elevations, as Golfyeti pointed out. For more details on the liver transaminase issue, see this post. It is also true that ASSURE trial failed to meet its endpoint to reduce plaque as measured by IVUS. However, the paper also fails to point out that apabetalone elicited robust effects for HDL/apoAI modulation and plaque reduction in those with low-HDL treated with rosuvastatin in ASSURE. It also fails to point out any of the post-hoc analyses of the Phase 2 trials that showed MACE reduction in the total population as well as in certain subgroups.

BDAZ