Expert Interview
A dive into the Amgen's OCEAN(a) study and the potential of olpasiran in treating patients with elevated Lipoprotein(a) and evidence of atherosclerotic cardiovascular disease (ASCVD)
Ticker(s): AMGNInstitution: Stanford
- Cardiologist and Instructor at Stanford University School of Medicine.
- Manages patients at the amyloid center at Stanford and directs the amyloid clinic at the Palo Alto VA.
- Research focuses on Investigating the molecular mechanisms behind genetic risk factors for human cardiovascular disease focusing on amyloidosis, cardio-oncology, and atherosclerotic diseases.
-- Background info on your expertise and details about your clinical practice and setting?
Can you speak about the importance of LP(a) and what's been established in the research on its role as a cardiovascular risk factor?
How many patients do you treat that have >150 nmol/L LP(a) even with your optimal statin/pcsk9 lipid treatment strategy?
Added By: user1ae2bf5fAmgen says LP(a) is elevated in 20% of the US population. Do you agree with this estimate?
What do you think might be LP(a) goal levels for a reduction that will confer clinical benefit?
Added By: user1ae2bf5fIn terms of CV risk from LP(a), how do you contextualize this risk vs. that of LDL? Are they correlated at all? Is the magnitude of each different or are they similar?
What do you make of the fact that drugs which decreased LP(a) significantly (Niacin and estrogen) did not impact CV outcomes?
There are a few conflicting studies on LP(a) risk in the context of low LDL, where in one study (AIM-HIGH), elevated LP(a) seemed associated with CV risk, but in another study (Nicholls et al) it was not. If benefit will be confined only to elevated LP(a) in high LDL setting, will there be any opportunity for these drugs?
Added By: user1ae2bf5fIn phase 1 single dose Olpasiran at 225 mg, which is the dose they used in phase 2, knocked down LPA by 94% at day 113. At day 155 it looks like around 80% possibly. That seemed to support quarterly dosing, and they went with every 12 week dosing in phase 2. Can you please comment on this?
Amgen recently announced phase 2 data. Namely, "a significant reduction from baseline in Lp(a) of up to or greater than 90 percent at week 36 (primary endpoint) and week 48 (end of treatment period) for the majority of doses."
What is your interpretation and how do you put this in the context of data from competitors like Pelacarsen (antisense approach)? Or Silence Therapeutics SLN360 (an siRNA)?
Is the safety profile a concern for Pelacarsen given the history of antisense oligonucleotide drugs? Is olpasiran potentially differentiated for better knockdown and safety?
Added By: user1ae2bf5fHow might payors treat a new expensive medication that would be given on top of LDL lowering meds?
Is there a threshold for the magnitude of CV Risk reduction in the phase 3 CVOT trials that you want to see to use Olpasiran or similar agents?
How would you design the phase 3 CVOT trial to best assess Olpasiran's utility?
Added By: user1ae2bf5fAre You Interested In These Questions?
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