Tada,

I am no expert on the ins and outs of how DSMBs work. It is unclear to me what data the DSMB sees, if early trial termination for futility can be done without a formal futility analysis, or if there is any threshold %RRR magnitude and/or statistical difference that warrants early trial termination due to overwhelming benefit. Based on the 9 DSMB reports to date for BETonMACE, it is likely, in my opinion, that apabetalone is not increasing risk of MACE in these high-risk patients and apabetalone is not causing any serious, unexpected adverse events deemed related to the drug with enough frequency to warrant trial termination. Beyond that, I do not feel like I understand the dynamic between the DSMB, clinical steering committee and Resverlogix, the BETonMACE statistical analysis plan, or the rules for clinical trial termination to comment further.

I keep referencing back to Amarin's REDUCE-IT trial for Vascepa. That trial had an amazing 24.8% RRR for the primary 5-point MACE endpoint with a p-value of 0.00000001; the secondary 3-point MACE endpoint had a 26.5% RRR with a p-value of 0.0000006. REDUCE-IT accumulated 1606 adjudicated 5-point MACE events, of which 1065 were 3-point MACE events, over the course of a median 4.9 years of dosing. REDUCE-IT had passed two previous Phase 3 trials for triglyceride lowering prior to starting REDUCE-IT. REDUCE-IT was not stopped early.

BETonMACE is only aiming for 250 3-point MACE event and will only have a median dosing period of ~2 years. Apabetalone failed to meet the primary endpoint of its most recent Phase 2 ASSURE trial, elicited modest effects on HDL/apo-AI primary endpoints in Phase 2 ASSERT and Phase 2 SUSTAIN, has never been tested in a previous Phase 3 trial, has a history of eliciting liver transaminase elevations, was discovered/announced to be a BET bromodomain inhibitor during ASSURE trial, and is the first BET bromodomain inhibitor in Phase 3 trials. Resverlogix would like to use this trial to file NDA/MMA submissions. We don't even know for sure if 3600 patient years (the original goal) have been met yet. I've elaborated further on the evolution of apabetalone in this prior post. These are all reasons why BETonMACE should go to completion without being stopped early. BETonMACE is a small and short trial relative to most cardiovascular outcomes trials, and it likely needs to go the distance to provide conclusive efficacy and safety data.

All just my opinion,

BearDownAZ