Emerging Lipid-Lowering Therapies: Advances in Lp(a) and Patient-Centered Care

In an Interview with Pharmacy Times®, Harpreet Bhatia, MD, MAS, FACC, preventive cardiologist from the University of California San Diego, at the American Heart Association (AHA) 2024 Scientific Sessions, shared updates on promising new lipids in development and making their way to the market, with an emphasis on lipoprotein(a) (Lp[a]) lowering therapies.

Pharmacy Times: What is your name and what will you be doing at the AHA 2024 Scientific Sessions?

Harpreet Bhatia, MD, MAS, FACC: My name is Harpreet Bhatia. I'm a preventive cardiologist from UC San Diego, here presenting a couple of different things related to lipids, particularly lipoprotein little A as well some work related to calcium scoring. And earlier this morning, I was helping to moderate a session on annual lipid updates for the AHA.

Pharmacy Times: Can you provide an overview of the most promising new lipid-lowering therapies that have recently entered the market or are currently in development?

Bhatia: I think there's a lot of exciting new therapies that have not yet come to market but are close and in advanced stage trials or close to even coming to market soon. So, I think it's a very exciting time in lipids. There's a couple of different drugs that are targeting different mechanisms of lowering lipids, whether it's lowering triglycerides, lowering LDL cholesterol or Lp(a), so there's a couple of different drugs aimed at targeting things like high triglycerides, like apoC3 inhibition. There are drugs that target triglyceride lowering as well as LDL cholesterol lowering, like ANGPTL3 inhibition. And then there's new drugs looking at CTP inhibition, which has been studied before. But some promise to these newer drugs that they might succeed where others had failed at lowering lipids across the board, but in particular LDL cholesterol.

And so, there's a lot of exciting hope for new options for patients, especially patients who are not achieving optimal lipid lowering with the current medications we have available, or even approaching new targets like triglycerides, where we don't have a lot of great options right now. Then, Lp(a) is, I think, the most exciting new area where we have no drugs available right now that specifically target Lp(a), and we have 5 to 6 new drugs in development, including the first drug pelacarsen (Novartis), which the trial is projected to close next year. And so hopefully we'll have information on that and whether lowering Lp(a) with a potent drug improves cardiovascular outcomes. Hopefully within the next year, we'll have information on that.

Lipoprotein particles | Image Credit: © komgritch - stock.adobe.com

Pharmacy Times: What are some of the most significant findings from recent dietary studies on lipid lowering?

Bhatia: There are a lot of exciting new drugs coming out for lipid lowering and being investigated, but it's always important for us to remember that lifestyle changes diet play an important role in cardiovascular disease (CVD) prevention. For diet, I tend to recommend people follow a heart healthy diet, usually following something like a Mediterranean style diet plan. I choose that because I think it has the most scientific evidence behind it, and has evidence not just for cardiovascular outcomes, but even for outcomes and things like dementia and cancer and all-cause mortality.

I also think it's a diet that's not a crash diet. It's not something that you can only follow for a short period of time. I think it's something that's a reasonable diet to follow, but really focuses a lot on plant-based foods, on healthy fats, replacing saturated fats with polyunsaturated fats, and things like that. Healthy sources of protein and lean meats, fish, things of that nature, healthy oils, as well. So those are the kind of things I generally recommend which have sort of strong evidence for improving cardiovascular outcomes over the long term in clinical trials.

Pharmacy Times: How do you approach patients receiving lipid lowering therapies to ensure they adhere to their treatments?

Bhatia: I think it's important to take a comprehensive approach to (CVD) prevention as a whole, and a lot of that is about communication, figuring out where patients are, what their beliefs and preferences are, what their goals are for the future, and really, my overall goal is to just reduce their cardiovascular risk by whichever method we take to do that. And so, I try to take a multi-pronged approach, definitely discussing what a healthy diet and healthy lifestyle looks like, as well as control sort of modifiable risk factors, things that people can do every day to have healthy behaviors. And so, a lot of it is kind of just communicating, seeing, what do they eat now? What kind of changes can they make? What is feasible for them? I think there's no one size fits all. So, it's really about meeting people where they are.

And then in terms of lipid lowering, I think a lot of it is understanding where patients are educating and figuring out what's going to work for them. And so, a lot of times, especially in secondary prevention, where we have aggressive goals for where we want their LDL cholesterol to be. For example, I tell people a lot of times diet and lifestyle is very important, but often to get people to these very aggressive levels, it usually requires medication, and we're fortunate to have a lot of different options for medication. So typically, talk about all the different options. Talk about sort of the realities of what insurance companies may cover or not, and how that reimbursement works, and how we might have to step through different therapies and try different therapies.

But I'm always willing to kind of work with patients if they're hesitant to start a medication, maybe start with a low dose, see how they do, and then adjust from there. Then, say you don't tolerate a medication. We're fortunate to be in an era of lipid lowering where we have other options, and we can move on to other options, depending on whether you achieve the goals or can tolerate the medications. So, it's all about communication and trying to set expectations up front that some of this is trying things, seeing what works, what doesn't, and then adjusting.

Pharmacy Times: What advancements in lipid-lowering research are you most excited about?

Bhatia: I'm definitely most excited I think about the Lp(a) lowering therapies. So, Lp(a) is a most common genetically inherited dyslipidemia. Because it's predominantly genetically determined, there's not a lot we can do in terms of diet, lifestyle, and not a lot we can do with current medical therapies that are available. It's a very prevalent disorder to have elevated Lp(a) estimated, at least 1 in 5 people have high levels. So, there's a significant unmet need. It's associated with multiple (CVDs), including coronary heart disease and aortic valve disease. So, there's a real need to approach this large population, find a way to mitigate their cardiovascular risk. And there's a number of drugs that are currently in phase 3 trials that show a lot of promise in initial studies in lowering Lp(a) very well.

And now the question is whether that lowering then translates into a reduction in cardiovascular events, which is the big question. But based on all the evidence we have up to now, we think that that's the case, but we're never sure until that's actually proven in a large clinical trial. So, we expect Lp(a)HORIZON (NCT04023552), the first trial of Lp(a) targeted therapy, to end around May next year, and then to have results, hopefully by end of next year. So, we're going to have a lot of answers to these questions coming up. And there's a lot of excitement about Lp(a) because it's such a significant unmet need and a target that we don't have treatments for right now.¹

REFERENCES

1. Assessing the impact of lipoprotein (a) lowering with pelacarsen (tqj230) on major cardiovascular events in patients with cvd (lp(a)horizon). ClinicalTrials.gov Identifier: NCT04023552. Updated October 1, 2024. Accessed November 19, 2024. https://clinicaltrials.gov/study/NCT04023552