"....why would safety and tolerability continue to be front and center after coming thru the BoM trial,,especially if BoM is a successful trial with no issues in the above parameters?,,,,,wouldnt the BoM trial prove that the two are/is a mute point?.....just thinking here."

The proposed apabetalone Phase 1/2 kidney trial will be in patients with end-stage renal disease (ESRD) treated with hemodialysis. All of these patients will have kidney disease that is even more severe than those that qualify as the chronic kidney disease sub-group in BETonMACE. An exclusion criteria for BETonMACE is "Evidence of severe renal impairment as determined by either eGFR<30 mL/min/1.7m2 at Visit 1 or current need for dialysis." The only trial to date that has dosed ESRD patients with apabetalone is the Phase 1 New Zealand trial, which was published earlier this year in Kidney Internation Reports and is entitled "Benefit of Apabetalone on Plasma Proteins in Renal Disease." These patients were not on dialysis though, so the proposed trial might be dealing with even sicker patients. The Phase 1 New Zealand trial only gave a single dose on day 1 to 8 ESRD patients and followed the patients to day 7. Therefore, the safety and tolerability of apabetalone for longer periods of dosing and with a larger number of these very sick ESRD patients still needs to be established. 

As for Fabry's and other new diseases/indications, it is common procedure to do shorter term Phase 1/2 trials first before proceeding to Phase 3 to make sure that safety/tolerability is still preserved in the context of a new disease. A disease such as Fabry's may affect various facets of physiology and cell biology that may perturb the normal pharmacokinetics of the drug and/or present unexpected side effects/adverse events. Apabetalone has been primarily tested in "normal" patients. So there is a burden of proof in the safety/tolerability department when apabetalone is being tested in "abnormal" disease states. In my opinion, even the low-HDL, type 2 diabetics in BETonMACE are relatively "normal" compared to the lesser understood/characterized, lower life-expectancy, severe nature of some rare diseases such as Fabry's disease.

BearDownAZ