Phase 3 BETonMACE trial did not meet its primary endpoint

The results of a placebo-controlled trial showed that apabetalone does not decrease cardiovascular (CV) death, non-fatal myocardial infarction (MI), or non-fatal stroke in diabetic patients with recent acute coronary syndrome (ACS).

Prof. Kausik K. Ray (Imperial College London, United Kingdom) presented the results of the phase 3, international, multicentre, randomised, double-blind, placebo-controlled BETonMACE trial. This study aimed to determine whether modulating epigenetics with the selective bromodomain and extra-terminal (BET) protein inhibitor apabetalone is safe and effective in reducing CV risk [1]. Patients with type 2 diabetes mellitus, ACS within the preceding 7-90 days, and low HDL-C (≤40 mg/dl for men and ≤45 mg/dl for women) were randomised to receive either apabetalone (100 mg orally, twice a day; n=1,212) or matched placebo (n=1,206) in addition to standard-of-care therapy, e.g. intensive or maximum-tolerated treatment with atorvastatin or rosuvastatin. The primary outcome of the study was the time to CV death, non-fatal MI, or non-fatal stroke. A key secondary outcome was time to CV death, non-fatal MI, non-fatal stroke, or hospitalisation for unstable angina or urgent/emergency coronary revascularisation.

Apabetalone changed HDL-C from baseline at 100 weeks by 16.2% versus 10.4% (P=0.001). Over a median follow-up of 26 months, the primary outcome occurred in 10.3% and 12.4% of patients treated with apabetalone versus placebo, respectively (HR 0.82; 95% CI 0.65-1.04; P=0.11). The rate of adverse events was similar across treatment groups, with 830 patients (68.5%) in the apabetalone arm and 820 (67.9%) in the placebo arm reporting at least 1 adverse event. However, discontinuation of treatment due to elevated liver function tests was more frequent in the apabetalone arm. The conclusion presented was that apabetalone has an adequate safety profile, and although HDL-C was significantly reduced from baseline at 100 weeks, no differences could be derived for patients with regard to CV death, non-fatal MI, or non-fatal stroke.

 

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   1. Ray KK, et al. Effect of BET Protein Inhibition With Apabetalone on Cardiovascular Outcomes in Patients With Acute Coronary Syndrome and Diabetes - Results of the BETonMACE Trial. LBS01, AHA Scientific Sessions 2019, 14-18 November, Philadelphia, USA.

Posted on 26 February 202013 June 2024