Good reply, but consider that PEARL and EMERALD were designed to be studied together and the hazard ratio of the combined study was 1.13 which is a trend to worse safety. If you cherry pick the data to just the dialysis setting you got a 0.95 hazard ratio. BUT they EMERALD study was open label, and open label studies are notoriously easier on the evaluated drug when it comes to safety. The drug made it through the FDA though so Kudos to AFFY, they put together a great submission file and convinced a not so easy panel, but now nephrologists are left to ask "Who is the sicker patient, a CKD patient not on dialysis or one on dialysis?" obviously the one on dialysis is sicker. Why would this population be BETTER off than a less sick population. When in doubt wait it out, is the right mantra here, let other people test the drug and use it when the drug is proven in the clinical setting. This would be fine for AFFY, except for the coming biosimilar competition. The timing just doesn't work. They can still hope for a take out so I would not short AFFY, but I would be taking profits.
Many of the points you made are being addressed in the post marketing studies. The time to achieve target hgb and variability are thus far looking like they may not be as problematic as once thought. Those conducting the post marketing studies are factoring in such issues as missed outpatient treatments after getting the monthly dose in their cost analysis and they will base their decisions accordingly. Also their have been studies where longer acting ESAs seem to consume less iron which would be another positive factor in cost analysis. Finally, there are about 10% of patients who receive dialysis at home and therefore are dosed less often and the longer acting ESAs are ideal for this situation.
As far as the studies showing poorer outcomes in CKD pts with omontys, there are many that are looking into the data. In the ckd studies, omontys was compared to Amgen's longer acting aranesp and omontys was dosed every month as it is in dialysis pts despite the fact that it is excreted by the kidneys. Aranesp, which has a similar half life as omontys in patients retaining significant renal function, was dosed every 2 wks and I have speculated that this is perhaps part of the reason for the discrepancy in the ckd studies. There are other hypotheses as well. The bottom line is that dialysis patients are not just sicker versions of ckd pts but are fundamentally different in that most have a procedure 3x per week and they have less , if any, remaining renal function. The FDA recognized this when they approved omontys only for patients with end stage renal disease. As we learn more, we could possibly see expanded indications but even without that I think there is a good chance for this company to do very well.