"I have a quick question. canakinumab is spoken about with great promise in this piece, published before the end of the CANTOS trial.  Do you recall if it was ever announced why continued testing of canakinumab was not pursued?"

Golf, the Wikipedia info from your previous post was far from the whole story. In the other article I linked to "Targeting Residual Inflammatory Risk: A Shifting Paradigm for Atherosclerotic Disease" they discuss the CANTOS results. Novartis' CANTOS trial proved that the anti-IL-1B antibody canakinumab reduced the inflammatory cascade and reduced 3-point MACE. See the full data press release here and the NEJM full article here.  They tested 3 doses of canakinumab in the trial. At a median follow-up of 3.7 years, 3-point MACE incidence was 4.50, 4.11, 3.86 and 3.90 events per 100 person-years for the placebo, 50-mg, 150-mg, and 300-mg canakinumab groups, respectively. Compared to placebo, 50 mg had non-significant 7% RRR, the 150-mg group had significant 15% RRR, and the 300 mg group had a non-significant (just missed significance) 14% RRR. These %RRRs were primarily due to significant reductions in heart attacks with non-significant trends for reduced CV death and stroke. Taken as a whole, the collective canakinumab groups proved that canakinumab works. However, if one scrutinizes the data it is not a home run.

As pointed out in the press release, as well as a publication on a pre-specified analysis based on change in hsCRP, patients that experienced a reduction of hsCRP to levels below 2 mg/L after 3 months of treatment experienced a ~25% RRR in 3-point MACE, 31% reduction in cardiovascular death and 31% reduction in all-cause mortality. Based on this, Novartis decided to pursue approval of canakinumab based upon this pre-specified sub-group analysis. However, the FDA slapped them down. So basically, CANTOS and canakinumab were successful from a clinical trial standpoint to prove that reducing inflammation decreased MACE; however, the FDA wasn't on board with the marketing application based on the high responder sub-group. Presumably, Novartis felt that the modest 15% RRR benefit in the total population was not commercially viable to pursue for cardiovascular indication. Kind of surprising that Novartis decided to abandon. There were some increased adverse events in the canakinumab groups, but nothing too worrisome. From this paper, "Overall, canakinumab was safe and well-tolerated. Although rates of death due to infection or sepsis were low, there was a slightly higher incidence of approximately one per thousand among those treated with canakinumab vs. placebo (incidence rate 0.31 vs. 0.18 per 100 person-years, p = 0.02). Of the different types of infections observed, only pseudomembranous colitis occurred more frequently in the canakinumab group."

Regardless of the reason for Novartis dropping canakinumab for cardiovascular indication, it is a great opportunity for apabetalone!

BearDownAZ