Dr. Kohli On The OCEAN(a)-DOSE Study

DocWire News Medical Lead, Dr. Payal Kohli, spoke about the OCEAN(a) DOSE study, which assessed the Lp(a) lowering safety and efficacy of olpasiran. The study was presented at the 2022 American Heart Association (AHA) Scientific Sessions.

Dr. Payal Kohli: OCEAN(a)-DOSE is a very fascinating study and done by, actually, former mentors of mine, Dr. Sabatine and Dr. O’Donoghue from the TIMI Study Group. And lipoprotein(a) is a nemesis that we’ve had in preventive cardiology for quite some time. We’ve not quite known what to do about it because we don’t know if it’s just a biomarker of risk or if it’s causally involved in the risk. Now we know, based on Mendelian randomization studies, that low levels of lipoprotein(a) are associated with better cardiovascular outcomes, and conversely, higher levels with worse cardiovascular outcomes, and also with aortic valve stenosis as well. So this was a study looking at an siRNA, a small interfering RNA, which is olpasiran. And the way that siRNAs work is they actually turn off the translation of the messenger RNA into the protein. So they get into the hepatocyte, the liver cell, and they basically prevent the messenger RNA from being turned into the protein. So they’re incredibly effective at lowering whatever their target is.

And the other siRNA that we have in cardiology is inclisiran, which lowers LDL. So this was an siRNA against lipoprotein(a). And it was basically a phase two study to see the tolerability and safety and the efficacy. How well does this medication work, and are patients able to tolerate pretty well? And the enriched patients who had elevated lipoprotein(a) at baseline, 88% of them were on statin. About a quarter of them were on PCSK9 inhibitors, which we know can also affect lipoprotein(a). And then they gave them different doses of olpasiran, the siRNA against lipoprotein(a), and the results were dramatic. We saw 71 to 97% reduction, some reports even of nearly a hundred percent or more reduction in lipoprotein(a).

So what we have on our hands is a game changer. And of course, my question is a preventive cardiologist is what about the outcomes? We’ve treated the number, but have we treated the risks? So that’s going to be the next step with this agent. The other question that comes to mind of course, is if you lower lipoprotein(a) by nearly a hundred percent, what does that mean? What does that mean for safety? What does that mean for long-term efficacy? But thus far, at least in this small study, which was a phase two study, the drug appeared safe. We only had some injection site reaction. So I’m really excited about the next step in this journey of lipoprotein(a) inhibition and really trying to figure out whether this is something we can start to give to our patients in a few years.