Nextblockbuster,

Yes, I understand your point. There are lots of positive, but also lots of negatives. Each milestone improves the confidence but there will always be the potential pitfalls along the way. I am not discounting the value of a positive futility analysis, just pointing out that from a clinical standpoint apabetalone still has many hurdles to go after the futility analysis. That being said, the market may respond in a totally different way and tends to exaggerate/amplify the impacts of crossing certain milestones. So a positive futility analysis (as well as other pending company activities) could very well cause a sharp change in the share price. Here's a quick brainstorm of the good and bad I see right now from the clinical trial perspective.

The good: Post-hoc analysis of ASSURE identified apabetalone + rosuvastatin in low-HDL patients as a synergistic combo/responder group for plaque reduction. Post-hoc analysis of ASSURE/SUSTAIN provided evidence of 5-point MACE reduction as well as identifying low-HDL diabetics as being optimal patient population. BETonMACE being done in patients with recent acute coronary syndrome event, which should boost event rates (also diabetic, low-HDL criteria should boost event rate too). Lots of clincal and pre-clinical data showing the many pathways (i.e. inflammation, acute phase response, complement, coagulation (thrombosis), atherogenesis, etc) that are beneficially modulated by apabetalone that should provide cardioprotection. Passed 3 DSMB checks so far (most recent mid-March 2017) with some patients on drug for as long as 16 months at time of DSMB report. No safety concerns as of yet other than the expected transient liver transaminase elevation. 18 months into trial. Enrollment going well with enrollment of 2400 patients expected to be completed H2 2017 and trial completed H2 2018 (barring any adjustments to trial design, enrollment targets).

The bad: ASSURE failed and the responder group (apabetalone + rosuvastatin in low-HDL pateints) only identified with post-hoc analysis. BETonMACE based on 3-point MACE (cardio death, non-fatal MI, non-fatal stroke) but almost all of the events in the ASSURE/SUSTAIN post-hoc analysis of 5-point MACE were not of the strict 3-point variety. Apabetalone is a first in class BET bromodomain inhibitor and long-term effects/safety are unknown and warrant increase scrutiny. BETonMACE is a relatively small cardiovascular outcomes trial and may turn out to be insufficiently powered; CETP inhibitor trials were very large consisting of over 10,000 patients. Futility analysis not done yet and no guarantee of slam dunk. Safety is no guarantee of efficacy; pattern of death, non-fatal MI and non-fatal stroke may not follow same predicted pattern as observed with the 5-point MACE post-hoc analysis. FDA/US study site involvement still an unresolved issue even after 18 months of dosing outside of US and repeated statements by Resverlogix that they are in discussions with FDA; this may be interpreted negatively.

BearDownAZ