I recently had the opportunity to catch up with management. Apparently the blinded data is all pointing in the right direction. 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).

Management is absolutely committed to reaching 250 total events so there is a risk the trial goes on a bit longer if the event rate continues to fall. However, the longer it goes on potentially the more powerful the results will be. 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).

Should be able to give top line results even if don’t reach 250 events (but will continue with trial until do reach 250 events). (Not sure I fully understood how you can give top line results before reaching the target number of events….). Still think will get to 175 events for interim review sometime this summer.  

Safety is fine – have now had 24 patients on Apabetalone for 2.5 yrs (1st patient Nov 2015). Interestingly the drug only really works when you are sick, it doesn’t really have much of an effect on healthy subjects. This is why Assure trial failed because 25% of patients weren’t that sick and had high levels of HDL.

Blinded data is also pointing in the right direction for the other end points – eGFR data “looks stunning, seeing amazing increases, unheard of”, cognitive improvement (MoCA test) data also encouraging (looking for >1.5 units improvement; anything <18 is considered Alzheimers).

Payors LOVE the fact that this is a SMALL trial. All these big trials are completely missing the mark because the Numbers Needed to Treat (NNT) are just too big and so all a Payor sees is a massive financial liability. If RVX can show a 30% decrease in MACE in 2 years that would be incredibly efficient.

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. If just look at sub-group of patients on SoC then the RRR was only 10% and the P value is insignificant. Look at supplement table in New England Journal of Medicine, pages 48, 66  “Supplement to: Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015;373:2117-28. DOI: 10.1056/NEJMoa1504720”.

If BetonMace achieved 25%-30% RRR with NNT of 50 then it would result in attractive payor economics. The Incremental Cost Efficiency Ratio (ICER), which measures how much extra money you need to spend over 1 year to save one event,  would be very interesting. i.e. if a hospital admission costs >$200,000 per patient then an interesting ICER is <$200k. For the big SGLT2 trial which lasted 5 years and had NNTs of 70 that equals 350 patient years to save 1 event, so if cost of drug is $3000/year that results in a ICER of $1m just to save 1 event. It’s NOT economic.

Working back from $200,000 hospital admission cost then a RRR of 30% and NNT of 50 (over ONE year) would support a price of $4000-$5000. If NNT is as low as 30 then Apabetalone could be priced at $6000-$7000 per year.  

Bottom line management think the value of Apabetalone is somewhere between $6bn-$15bn. Current value of company, using fully diluted share count, 30m debt is c.$350m USD. So my PT for RVX is  CAD 8bn – CAD 20bn = CAD 30 – CAD 90 per share. But have to discount by 12% due to Zenith claim on Apabetalone so CAD 26 - CAD 79.