Iconoclast,

Thanks for the reply and opportunity to discuss these issues. There is a lot to still be determined between now and when the NDA/MMA are filed and approved with the FDA/EMA. Because of this uncertainty, I am only pointing out generalities here. I'll leave projections of market $ and patient number potential to others. A lot can change depending on the %RRR for BETonMACE primary outcome, and how BETonMACE pre-specified sub-group analyses and secondary outcomes pan out.

What we do know is that all BETonMACE patients are type 2 diabetic, low-HDL being given apabetalone as secondary prevention after an ACS event within 90 days. Therefore, one interpretation in the short-term (maybe not the only one?) is that apabetalone will not be approved for those who are not diabetic, not be approved for those with normal HDL, not be approved for those with CVD risk factors but who have not experienced a prior MI/stroke/ACS event (primary prevention) and not be approved for those who have experienced an ACS event greater than 90 days in the past (even if they are diabetic, low-HDL). I hope you can appreciate what I am pointing out here. If the only Phase 3 trial for apabetalone to date is BETonMACE, and if BETonMACE is comprised of such a narrow, high-risk pool, then it may not be possible to immediately gain FDA/EMA marketing approval to expanded populations outside of the restrictions I summarized above. More trial may be necessary for marketing approval. However, post-BETonMACE Resverlogix/apabetalone could still be valued for this future potential of expanded populations. Valuation and marketing approval are related, but distinct animals.

As for the CKD indication, keep in mind that a follow up Phase 3 trial (BETonRENAL? BETonCKD) may be necessary for apabetalone marketing for CKD indication. The BETonMACE CKD substudy is assessing changes in kidney function in a stage 3 CKD patient population (~250 patients) with eGFR below 60 mL/min at screening. Change in alkaline phosphatase (ALP) and eGFR as well as serum chemistry markers and inflammatory markers will also be included in the analysis. The occurence of the primary MACE outcome in the eGFR>60 and eGFR<60 subgroups will also be analyzed. BETonMACE CKD patients will all be diabetic, low-HDL, and recent ACS event. To prove its safety and efficacy in a wider CKD population, a larger trial without such stringent limitations may be necessary.

All just my opinion. I hope this helps. Merry Christmas and happy holidays to all! 

BearDownAZ