That is amazing Tundup. Thank you so much for inquiring with Resverlogix, getting these details and sharing. What frustrates me is why Tundup has to be the one to communicate these very helpful pieces of information. I'll need to read and re-read this to fully appreciate, but for now here are a few comments. Thanks again Tundup! You are awesome!

"The rate of MACE events has been dropping steadily since the beginning of the trial, starting off at the expected 8% per 100 patient years but now down to 7.2% per 100 patient years (originally expected to see 10%-11% MACE event rate)."

The original 10-11% event rate projection was an 18 month event rate. As I've pointed out before, this is distinct from expressing an event rate as per 100 patient years, which is more equivalent to an annual 12 month event rate. It was already known based on the EXAMINE trial and other trials of high-risk cardiovascular patients that the greatest risk for experiencing a 3-point MACE event is during the first 9 months of the trial. After this first 9 months the risk of an individual patient levels off. See below from EXAMINE, which shows the time in trial (observed % event rate):

3 months (2.5%)

6 months (5%)

9 months (8%)

12 months (9%)

15 months (10%)

18 months (11%)

21 months (12%)

24 months (13%)

In other words, when the trial first started and when new patient enrollment was zooming along the rate of MACE accumulation was highest. But as enrollment slowed/completed AND as more patients progressed passed the ~9 month mark, the rate of MACE accumulation slows. Therefore, the observed drop off from ~8 per 100 patient years to 7.2 per 100 patient years makes perfect sense.

"Regulator has told RVX it needs 3300 patient years vs currently at 2400 years. Should reach 3300 patient years by end of this year (getting 7 patient years every day now, so +210 years every month)."

I'm very happy to hear an update on the # of patient years. My conservative estimates based upon the enrollment updates was that BETonMACE would be at 2663 patient years by end of June. It seems that I wasn't conservative enough. I did not account for patient deaths or drop out, which could partially explain the discrepancy. When did you talk to management? Just curious so that I can put an approximate time stamp on that 2400 number.

"Still think will get to 175 events for interim review sometime this summer."

If true, then the SSRA may still be on AND we can infer that they haven't yet met the number of required events to trigger the SSRA. However, they have previously communicated several times that the interim review (SSRA) is at 75% of the planned 250 events, which is 188 events and not the 175 events that you wrote. Even with the revision to my patient year estimates above, I still see the 188 events being hit any day now. Today is the first day of summer!   

"The Lilly SGLT2 trial was a complete fraud – 30% of the patients weren’t on standard of care, not on statins, not on beta blockers/ACE inhibitors/Pavix etc."

That is very harsh criticism of the SGLT2 inhibitors. I am not saying what you wrote is completely wrong, but I am somewhat skeptical of the "fraud" claim since I haven't heard any criticisms like these from cardio/diabetes professionals. In addition to EMPA-REG OUTCOME with Lilly's empagliflozin, the CANVAS trial with Janssen's canagliflozin showed clear benefits. More recently, the CVD-REAL (Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors) in patients on either empagliflozin or canagliflozin concluded "In this large, multinational, observational study, initiation of SGLT-2i was associated with lower risk of death and HF regardless of pre-existing CVD." That being said, both EMPA-REG OUTCOME and CANVAS only achieve 14% RRR in 3-point MACE in the diabetic patients. So if BETonMACE indeed achieves 30% RRR, then watch out world!

BearDownAZ