Like it or not, SGLT2 inhibitors are a competitor for apabetalone. SGLT2 inhibitors reduce MACE in diabetics. We already knew this from the various diabetes CVOTs for SGLT2 inhibitors that have reported results over the past few years. Additionally, there were hints of improved renal outcomes in the secondary and exploratory analyses of these trials. CREDENCE for canagliflozin is the first renal outcome focused follow up trial to report data. However, empagliflozin and dopagliflozin have ongoing renal outcome focused trials that will report in the future. CREDENCE results don't really directly affect apabetalone, but are likely more relevant to canagliflozin differentiating itself from its sibling empagliflozin and dopagliflozin SGLT2 inhibitors in the short term.

One observation in CREDENCE is that 3-point MACE occurred in 12.2% of placebo patients at median follow up of 2.62 years, which works out to 4.66 events per 100 patient years. That's a high event rate, but BETonMACE patients will have an even higher event risk rate due to low-HDL and recent ACS requirements. Canagliflozin elicited a 20% RRR for 3-point MACE in CREDENCE, a bit better than the 14% RRR that canagliflozin and empagliflozin elicited in CANVAS and EMPA-REG OUTCOMES, repsectively. Still, if apabetalone elicits a 30% or greater %RRR in BETonMACE, this will be spectacular and unprecedented in this patient population.

Plus, canagliflozin in CREDENCE only slowed the decline of eGFR and did not increase eGFR. If apabetalone can not only do this but actually increase eGFR in CKD patients, then this will be an amazing accomplishment.

BearDownAZ