Full Transcript Introduction to Lp(a) and Why It Matters 0:00 Hello, everybody. Welcome. 0:01 This is the host of Reversing Heart Disease naturally 4.0 Joel 0:05 Kahn 2026 data to help you 0:08 guide your heart and your health long term. 0:11 So we're going to talk about exciting data about upcoming therapies 0:16 for a particular inherited cholesterol that I've had a great interest in. 0:21 And about it, up to a third of you have a great interest in, 0:25 because you may know your blood level of light bulb protein, little A or LP, 0:30 little A, and you know that it's elevated and you know that it's inherited. 0:34 You know that even an optimal diet and exercise might not take care of it. 0:38 And you've heard that there may be new drugs coming down 0:41 the pipeline from pharmaceutical companies 0:44 that may deal with this problem in the meantime. 0:47 And we deal with it quite effectively at the center for Cardiac Longevity 0:51 with various, vitamins, adjustment of prescription medications and lifestyle. 0:56 But we still need better approaches. 0:58 So let me share with you a brief presentation 1:02 on what we are looking forward in 2026 and beyond for the therapy of up 1:08 to 30% of people around the world that inherit from mom, dad, or both. 1:13 The ability to make OP little a a light bulb protein, little light. 1:18 If you look to the right, what's the big deal. 1:20 Because light bulb protein little aid can cause heart attacks.
Current and Emerging Lp(a) Therapies 1:24 That's called an MI, a stroke, 1:27 aortic stenosis, a valve problem, and abdominal aortic 1:30 aneurysm a serious problem and blockages in the legs. 1:34 Around the world, 10 to 30% of people inherit lipoprotein little. 1:39 The highest is in Africa, and it's estimated it's about 1.5 billion people. 1:45 We might need a therapy for those and inherit the ability 1:49 to make lipoprotein little and are developing atherosclerosis. 1:53 Not all people develop atherosclerosis, 1:56 but we have the ability to detect who is. 1:59 So although this, cholesterol particle was discovered in 1963, 2:04 it took about 50 years. 2:06 2015 the pharmaceutical company called Novartis 2:11 created a drug, an antibody to lipoprotein, little AA 2:15 that lowers lipoprotein little, and that is called pellet Carson. 2:19 And that began a series of investigations on this drug. 2:23 But there are as listed here are four other injectable drugs. 2:27 And then ultimately something called gene editing. 2:31 Maybe if you make lipoprotein little eight, 2:34 we can shut off the gene on chromosome six and you stop making it. 2:38 So these drugs that have been developed are very powerful at lowering lipoprotein 2:43 little AA up to 95% reduction in the blood level of elevated lipoprotein. 2:49 They lie through a variety of mechanisms. 2:51 But the FDA requires not just proof that it lowers lipoproteins, 2:56 but that it actually reduces heart attack, stroke, death bypass, and stents. 3:00 So pellet cars, and ultimately through a very complex 3:04 and fascinating pathway, reduces the production of lipoprotein level eight. 3:10 If you look to the left, 3:11 what's called a phase two trial, I had patients in the phase two trial, 3:16 286 patients with heart disease, elevated lipoprotein little. 3:20 I got a variety of doses of, pellet Carson 3:25 over the course of about 12 to 24 weeks. 3:28 This was published in 2020.
Pelacarsen and the Horizon Outcomes Trial 3:31 And they showed the average. 3:32 Lowering the lipoprotein level was a dramatic and powerful 80%. 3:37 So the FDA gave a green light. 3:39 Go do a study. 3:40 Novartis and Switzerland go spend $1 billion 3:43 and find out if your drug prevents strokes and heart attack. 3:47 So 8323 people are enrolled. 3:51 They have an elevated lipoprotein little a significantly mean age 3:55 of 6,027% female, 78% are white. 3:59 Why did you have to have to get in the study a very high lipoprotein, 4:03 a genetic cholesterol level and this important a previous heart attack 4:07 called an Am, a previous stroke, symptomatic blockage in your legs. 4:12 So it wasn't just your blood test is abnormal. 4:14 You had already have an event of course, this means you're a high risk patient. 4:19 They got injected with either placebo or pellet. 4:22 Carson once a month. 4:24 And there's an end point. 4:25 And if you notice the slide says in the top right 4:29 expected results February 2026. 4:33 We actually thought this was going to be announced 4:35 in May of 2025, but the company delayed everything a year. 4:39 We don't know why, and we're eagerly awaiting these results. 4:42 Could be any day. 4:44 Could even be by the time, reversing heart disease. 4:47 Naturally, summit is released 4:49 because I'm recording this very soon before the release of the summit. 4:54 If you look 4:54 in the lower right box, there are people that have a condition 4:58 called aortic stenosis because they have elevated lipoprotein little like. 5:03 So there's a separate study to see if Pellet Carson 5:06 will protect the aortic valve in people with high lipoprotein level 5:11 and some degree already of calcification of their aortic valve. 5:18 All right. What about a second drug? 5:19 You don't have to remember every one of these pellet. 5:22 Carson is a one we're interested in.
Olpasiran, Lepodisiran, and Other Injectable Drugs 5:24 All person has a different mechanism of shutting down lipoprotein production. 5:30 In a phase two trial on the left, 281 patients mean age is 62. 5:36 It was greater than a 95% reduction in lipoprotein 5:40 level A with the injection of this drug every 12 weeks. 5:44 So the FDA said go for it. 5:46 This is, a company called Amgen. 5:49 See if you can prove to us that you can prevent strokes and heart attacks. 5:53 So this study got off two years after the pellet Carson study. 5:57 We're hoping by the end of this year we'll have the results 6:00 7297 patients, a high rate of protein 6:05 little a similar to the pellet Carson horizon study. 6:09 Previous heart attack, previous stent 6:12 or other risk factors like diabetes and smoking. 6:14 The hypertension I require. 6:17 We'll see what happens with this. 6:20 And it may be by the end of this year we'll have the results. 6:23 It's a different chemical. 6:25 It's a powerful chemical. 6:27 But we have to prove the clinical value. 6:29 Many people are excited about this drug called 6:31 lipid decisions made by Lilly in Indianapolis. 6:35 It lowers lipoprotein A and volunteers 320 volunteers 6:40 who took it for a number of weeks by 94%. 6:44 So Lilly has designed a trial with almost 17,000 people, 6:49 a high lipoprotein, little a they either already had an event like a heart attack, 6:54 or they were over age 55 and they had a high cholesterol and other 6:59 risk factors, and they only get injected every 6 to 12 months. 7:04 And it's not just about lowering label protein. 7:07 A, it's about events. 7:09 So we don't have those results yet. 7:11 You can get into that study 7:13 the LA Pedestrian Lilly study I've enrolled many people in it. 7:17 There's a preliminary lipoprotein level, 7:21 a small inhibitory RNA molecule called sterilizer. 7:25 In another drug. 7:26 They've done their phase two trial, a 95% lowering of lipoprotein level 7:32 with the injections usually about every 12. 7:36 So they will probably move on to these phase 7:39 three massive trials, this drugs further down the pipeline.
Oral Lp(a) Inhibitors and Gene Editing 7:43 And some people don't like to inject themselves. 7:46 So there is an oral version of a light 7:50 protein little AA inhibitor drug called mobile app. 7:53 When it went into trials a few years ago, it binds 7:57 to a component of lipoprotein that lead to prevent 8:01 the full formation of lipoprotein like. So. 8:05 This is what the future looks like. 8:08 It's in a phase three study. 8:10 Now there are around 450 people. 8:14 They had a high lipoprotein level. 8:16 They either had a prior event, like a stroke or a heart attack, 8:20 or they had a high calcium score and other risk factors. 8:24 They'd take their pill daily or the placebo. 8:27 And maybe by 2031 we'll have the results. 8:30 Now remember, when these drugs, if they get approved, 8:34 they're all patented, going to be very expensive. 8:37 And the average person doesn't meet all these criteria. 8:41 The average person, a lipoprotein, that little lady hasn't had a heart attack 8:45 or a stent or a bypass. 8:46 So I think it's going to be quite a while to see these drugs used widely 8:50 and very long time to see a generic version, 8:53 because I'll be patent protected, of course. 8:57 So the final potential is that gene editing 9:03 we make a lipoprotein little a and up to 30% of people, 9:06 because we have a gene we inherited that allows us to reproduce. 9:10 What if you can edit the gene and turn it off? 9:14 So there's very early human studies really ongoing that 9:19 with an infusion that alters our DNA and there's great concern about that. 9:25 We can shut off lipoprotein production and it will be shut off 9:29 at least for a year, but probably permanently. 9:33 There have been issues with, liver enzyme elevation with this approach. 9:38 So we have to be very cautious. 9:40 So just an overview of the landscape. 9:43 If you look at the top, the pellet 9:46 in Carson Horizon trial we hope will be announced very soon.
What Comes Next for Lp(a) Treatment 9:51 And then there are the other studies coming. 9:53 The ocean a study we reviewed all these I didn't give you the name of 9:57 every one of them. 9:58 The Moffitt Lapland study is called the move LPA study. 10:02 And now there's good tolerability major lipoprotein reduction. 10:07 But will these drugs prevent events. 10:10 And that's what this said. 10:11 Looking ahead to the future will lipoprotein a lowering 10:16 reduce the risk of cardiovascular disease death 10:19 aortic valve calcification and other manifestations. 10:23 We have to find out soon. 10:25 Many people need this. 10:27 In the meantime, find somebody who's expert in managing lipoprotein little life 10:33 and certainly manage your lifestyle optimally with nutrition and fitness 10:38 and sleep and stress management and all the other protective mechanisms 10:42 that we talk about. 10:43 So I'm going to say thank you very much for joining me on this talk. 10:48 And I hope by next year, reversing heart disease. 10:51 Naturally, summer 5.0, we actually can celebrate the release 10:55 of 1 or 2 of these medications that will help people significantly. 10:59 That's the help.
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