Re: CVD, kidneys, and doctors... oh my!
in response to
by
posted on
Nov 19, 2019 06:18PM
Deb,
Thanks for a much-needed voice of reason from, I'm presuming, a physician. We have a drug trial that failed and a broke company; we don't need a BP conspiracy or FDA indifference or academic incompetence to explain current share price. The company will be funded, I’m sure, but the market needs to know the dilution factor in order to estimate the value of existing shares. And so we wait for funding news… Personally, I am quite pleased that share price has stood up so well so far and I think that is based on the positive indications that came out of the study. Regardless, what we have are positive indications (none significant if tested properly) and no money. Let's deal in reality.
As interesting in most studies as the successes (expected outcomes) are the failures (unexpected outcomes). Let's focus a bit on failure: where did apabetalone fail to work? A simple answer was given in the presentation: apabetalone didn't reduce strokes. Over all patients that is certainly true, you can't get more even than 17 strokes in the treatment group and 17 in the placebo group. A hazard ratio of 1. End of story?
Not quite. There are two things to consider here.
1. In both subgroups in which apabetalone performed well (CKD patients and low LDL patients), apabetalone did provide an apparent stroke benefit and a large one at that. From slide 22 for the renal subgroup, strokes were 2/110 in the apabetalone and 6/153 in the placebo group for a HR of 0.47. In terms of magnitude of effect, this is better than the HR of 0.53 for the other two MACE components combined (CV death, non-fatal MI). From slide 32 for the low LDL subgroup, strokes were 5/594 in the apabetalone and 9/597 in the placebo group for a HR of 0.56. Again, in terms of magnitude of effect, this is better than the HR of 0.60 for the other two MACE components combined (CV death, non-fatal MI) in this group. However, because so few strokes occurred, these reductions in strokes were not significant and, quite rightly, will need to be confirmed in future studies.
2. The low number of strokes overall is also pertinent in another way. Stroke was the minor MACE event in this study compared with CV death and non-fatal MI. The fact that stroke number did not differ between the control and apabetalone groups overall did not sink the study. What sunk the study was that apabetalone showed no efficacy for any MACE component in a much bigger portion of patients than those affected by stroke.
That’s another story…
Jupe