New ASCVD drugs oozing out of the pipeline

So everyone here has had the opportunity to read about Lp(a) as a genetically determined risk factor for ASCVD…along with the value of a once only measurement to refine individual risk assessment beyond the Usual Suspects in a lipid profile.

I had an idea that this was a therapeutic target (my intervention cardiologist mentioned it a few months back) but, apparently its time has come. I’ve only had a chance to read snippets of information so far and my go-to internet edutainers haven’t addressed it yet. Might be a profitable venture for some of us in more ways than one.

Of course, if you’re one of the fortunate majority who aren’t in this risk demographic, might not be so interesting.

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Four nucleic acid therapeutics — all administered subcutaneously — are now in clinical testing, as follows:

  • Pelacarsen. This antisense oligonucleotide, given once monthly, is being studied in the phase 3 Lp(a) HORIZON outcomes trial (NCT04023552) in a collaboration between the Cleveland Clinic Coordinating Center for Clinical Research (C5Research) and Novartis. Results may be available in 2025.
  • Olpasiran. This siRNA, given every 12 weeks, is being assessed in the phase 3 OCEAN(a) outcomes trial (NCT05581303). Results are expected in 2027.
  • Zerlasiran. This siRNA (dose frequency still to be determined) is being studied in a phase 2 trial coordinated by C5Research and Silence Therapeutics.
  • Lepodisiran. This siRNA, which can likely be given once or twice a year, is being evaluated in a phase 2 trial (NCT05565742) in a collaboration between C5Research and Eli Lilly. A phase 3 trial is also being planned.

Lepodisiran is particularly intriguing, says Dr. Nissen, who presented results of a phase 1 trial of the agent at the American Heart Association Scientific Sessions 2023 (also published in JAMA. 2023;330:2075-2083). “A single dose of lepodisiran lowered Lp(a) to a level undetectable by the standard assay from day 29 to day 281 following administration, and to a level 94% below baseline at the end of the 48-week study,” he says. “This is an unprecedented degree and duration of Lp(a) reduction, which suggests lepodisiran could potentially be given once or twice a year, like a vaccine.”


Me and coincidences. So, here’s a newly delivered article by one medical writer I follow reviewing a book written by another I also follow on ASCVD and its prevention. For sure, without the updates to my knowledge base on current understanding of lipidology, my ASCVD would surely be marching towards a major cardiovascular event…if it hadn’t already happened.

How are you going to determine you are not fully on the guineapig side of testing these drugs? How much time on the market will you allow to determine what is safe?

Personally, I shall listen to the advice of my chosen medical advisor. There’s inevitably going to be someone first on line for treatment. I doubt it needs to be me since the medications I’m currently taking seem to be doing the job they’re supposed to without noticeable side effects. If that weren’t the case…or if my disease status happened to be more advanced…I might need to reconsider.

Folk who happen to be fortunate in the genetic hand they’ve been dealt don’t need to balance the odds like this. Lucky them.

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Hopefully things stretch out a lot timewise. Then you get to know which of these drugs is the safe.