New Lp(a) lowering drug

Eli Lilly’s experimental therapy lepodisiran reduced the harmful risk factor for lipoprotein (a) by up to 94% for up to a year with just a single dose, data from a first-in-human trial has shown.

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Heart disease will be a thing of the past by the end of this decade.

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Love :heart: the one dose a year, shame all drugs can’t be like that

Perhaps the drug has a very long half life?

That’s amazing! I can only imagine the cost of that once yearly injection, though.

Eli Lilly also has a small molecule ( Muvalaplin) in the pipeline (phase 2, I think) as well:

Novartis has a phase 3 study of their drug (Pelacarsen) set to be completed in May 2025:
https://clinicaltrials.gov/study/NCT04023552

Additionally, Amgen has a drug (Olpasiran) in phase 3 set to be completed in Dec 2026:
https://clinicaltrials.gov/study/NCT05581303

These phase 3 studies are being done in patients that have elevated Lp(a) and heart disease. It is unclear if lowering Lp(a) will have a profound impact on lowering the number of events in these patient populations. The Novartis trial started in late 2019 and has been going for four years. They have not stopped the trial, so there likely have not been issues with severe adverse reactions. That said, it likely is not producing a profound benefit relative to the placebo group.

Hopefully they end up working well and the lowering of Lp(a) does have a robust clinical effect. I personally have elevated levels. There’s not a lot of emphasis on testing for this in the United States. Some of this could be due to there not being any proven treatment to address the issue.

There does appear to be a relatively strong relationship between elevated Lp(a) and coronary artery disease and heart valve calcification. Hypertension alone but also in the context of elevated Lp(a) is definitely not a good thing to have. There was a study published in in late 2022 that examined the effects of elevated Lp(a) in the MESA study population:

Association of Lp(a) (Lipoprotein[a]) and Hypertension in Primary Prevention of Cardiovascular Disease: The MESA

summary:Elevated Lp(a) Can Increase Cardiovascular Risk in People with High Blood Pressure

Upon analysis, results indicated there was no increase in risk for cardiovascular disease events for those with elevated Lp(a) and no hypertension relative to their counterparts without elevated Lp(a) and no hypertension in fully adjusted models (HR, 1.09 [95% CI, 0.79-1.50]). In contrast, when compared to those without elevated Lp(a) and no hypertension, results indicated those a statistically significant increase in cardiovascular event risk was observed among those without elevated Lp(a) and with hypertension (HR, 1.66 [95% CI, 1.39-1.98]) as well as those with elevated Lp(a) and with hypertension (HR, 2.07 [95% CI, 1.63-2.62]). Further analysis suggested those with elevated Lp(a) and with hypertension had an increased risk of cardiovascular disease events (HR, 1.24 [95% CI, 1.01-.153]) relative to their counterparts with hypertension but without elevated Lp(a).

“We found that the overwhelming amount of cardiovascular risk in this diverse population appears to be due to hypertension,” Rikhi said. “Additionally, individuals with hypertension had even higher cardiovascular risk when lipoprotein(a) was elevated. The fact that lipoprotein(a) appears to modify the relationship between hypertension and cardiovascular disease is interesting, and suggests important interactions or relationships for hypertension, lipoprotein(a) and cardiovascular disease, and more research is needed.”

edit: Here is a calculator that may provide some insight in to how elevated Lp(a) can increase the risk of heart attack or stroke:

https://www.lpaclinicalguidance.com/
Novel AI algorithm could help personalise the prevention of cardiovascular disease

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Those drugs will likely be used in addition to statins/PCSK9i in the future like ezetimibe.

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Very skeptical of this statement. There have been drugs out there for ages (heart and CVD drugs) yet it is still the number one cause of death in USA. As long as people will stuff their mouths with donuts fried in vegetable oil and keep eating those burgers made loaded with chemicals there will always be heart disease no matter what drugs come to market.

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Heart disease is still the number one cause of death because people start the therapies when it’s already too late and soft plaque is already all over your blood vessels. With the emerging therapies, apoB will be crushed to nil and existing plaque will be cleared up much more efficiently.
By the way, vegetable oil may actually be pretty good for heart health. It’s saturated fat sources you need to watch out for.

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I’m guessing that your comment is a little tongue in cheek although obviously I hope you are right! Apparently some cardiologists were saying similar things in the 1990s courtesy of statins. And yet here we are :roll_eyes:

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One day people will get a flu shot and a LPa shot

New X thread from the King of Lp(a) at this year’s American Heart Transplant Congress:

Def worth a quick skim:

https://twitter.com/lpa_doc/status/1724204165910409515?s=46&t=zJMJ1xVdRJYEDYz-DHipTw

So it lowers lp(a) but does it increase lifespan or at least healthspan?

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Not according to all health doctors on YouTube, and no they don’t have any interest to promote say meat since I doubt any of them owns any cattle farms (last time I checked). For me, as far as food goes I try to simplify things. For example, make the nicest and juiciest steak with all the dressing and sauces etc. and go to a farm and feed it to a cow, or a sheep, or a goat if you like. Guaranteed our superior cooking skills will mean nothing to those animals and none will eat it. By the same talking, give a human salads/grass (meant to be eaten only by animals) and they will gladly eat it and even say oh it is so healthy LOL. Well, if a cow would not eat my food, why on earth would I eat a cow’s food, I think it is only fair :slight_smile: Having said that, there is plenty of plant foods that are very good and healthy and made for human consumption IMO, such as nuts and seeds, fruits and vegetables (not the grassy ones, i.e. salads those are cows food). Never liked salad, and never will hahaaa. My two cents.

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I don’t think anyone is promoting Lp(a) lowering drugs as general geroprotective/anti-aging compounds. It’s a very specific target for a very specific purpose (cardiovascular disease in people with high Lp(a)). Why would they increase life span? The question currently being investigated in clinical trials is if they decrease CVD events; if so (and barring any side effects), then I’d consider it a win for health span.

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There’s a case to be made that heart disease is still the number one cause of death because modern lifestyles ruin the health of our Endothelium. Eat high-carb crap, be sedentary (stare at screens all day for both work and recreation), get stressed out practically every day of your life and yes those apoB particles will take their toll on your poor suffering blood vessel linings.

So of the two routes, which is an easier way to reduce ASCVD risk? Totally change one’s lifestyle to be healthy/optimal for our species, including food, sleep, modern stresses, exercise, etc., or take some drugs to lower your apoB? I suppose most of us (including me) will choose to take the pills/shots to “crush” our apoB. It’s easier and I can continue to enjoy my modern life/environment that is completely different than what my genes are optimized for.

Personally I see our modern life choices as the cause of not only ASCVD but a significant source of human suffering. Yet when PCSK9 inhibitors (and their successors) become available to me, I’ll be signing up as my Lp(a) is relatively low but my LDL-C is quite high.

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Good post, fellow salad hater! :sweat_smile:
Honestly, I have eaten salads most of my life and even ate out at restaurants that featured salad bars.
As I haven’t gotten old my tastes have changed. I don’t like salads, especially salad dressings. Now I eat what I want and I eat meat and other non-veggy sources of protein. I am a keto/carnivore because I like that, not because I necessarily think it’s the best way to go

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Funny you mention that as we get old/older tastes change. I used to hate anything seafood or fish. I’d rather go without food than eating fish in my very young years, and it did not even sit well with me, in rare cases I would force myself to eat it.
Fast forward couple years (more like 40) and fish is the food that I digest the easiest and sits best with me than any other food out there (i.e. meats and veggies). Indeed, tastes do change, I also used to love brunnetes and now love blondes. :slight_smile:

Gene editing therapy seems to be gaining some traction.

Goodbye Statins? New Gene Editing Therapy Slashes High Cholesterol (msn.com)