Explained: How close are we to treating a lipoprotein that can kill?

Why seemingly healthy Indians in their forties and fifties suffer from sudden heart attacks - often fatal - is often blamed on things like sedentary lifestyle, genetic factors and diet. However, doctors have long suspected there’s a factor that often goes unchecked and might be a leading cause for premature heart attacks: a lipoprotein that transports cholesterol. Lipoproteins are complex particles made up of lipids (fatty compounds) and proteins that enable the transport of cholesterol and fatty acids throughout the body. While cholesterol is popularly linked to blocked arteries and veins, it is also essential for the normal functioning of cells in the body. Because fats are insoluble in water, they need to be carried by these specialised particles.Cardiologists say that imbalance in Lipoprotein (a) levels - or Lp (a) levels - may be the cause of premature heart attacks among Indians and other South Asians. But there are now multiple experimental drugs that are promising to almost eliminate this risk factor entirely. medium nocaption113982176How much of a factor is Lp(a) in heart attacks? A 2019 study led by Dr Basil Varkey of the Medical College of Wisconsin and Dr Enas A of Downers Grove, Illinois, said that Lp(a) levels were found to have a consistent relationship with coronary artery disease (CAD) and heart attacks among Caucasian people. Lp(a) is generated by the human liver. The study said people from South Asian populations were at a higher risk from heart attacks and coronary artery disease at younger ages despite having lower Lp(a) levels. The study said elevated Lp(a) levels among Indians may be the strongest genetic risk factor for premature coronary artery disease (CAD) and may be resulting in fatal heart attacks that occur earlier. The study also noted that the lipoprotein levels were often undiagnosed but could be crucial in understanding why heart disease is so prevalent, and deadly, among younger Indians.“People who have elevated lipoprotein levels have a 2-3 times higher incidence of heart disease and almost 20-25% of Indians have elevated lipoprotein levels,” Dr Prashant Pawar, an interventional cardiologist at Fortis Hiranandani Hospital in Navi Mumbai had told TOI+. However, awareness about this lipoprotein affecting heart health is low and few doctors test for it since there is no obvious treatment plan for it. Treatment for high Lp(a) levels were mostly lifestyle related, like lowering fat-rich foods, increasing vegetable and fruit consumption, and exercise. medium113980298However, there’s no conclusive evidence that either diet or exercise make a significant impact on this factor. Why an experimental drug offers hopeNow, an experimental drug made by Eli Lilly, called lepodisiran, is promising to lower levels of Lp(a) by 94% with a single injection. The effects of the drug are said to have lasted for six months and there were no significant side effects.The pharma company presented its research recently and is now starting to conduct large clinical trials to confirm that reducing Lp(a) levels will reduce the risk of heart attacks and strokes. The trials will end in 2029. "What we have is a drug that can lower lipoprotein(a) with very infrequent administration," study author Dr Steven Nissen, a long-time cardiologist at the Cleveland Clinic, said in an interview. Dr David Maron, a preventive cardiologist at Stanford not involved in the Lilly research, said the evidence of profound and long-lasting reduction in lipoprotein levels with lepodisiran was “thrilling.”Is this the only drug that promises to tackle this issue?There are at least four other companies that are also testing their own products that block the body’s production of Lp(a). Some of these drugs are already in clinical trials which will end sooner than Eli Lilly’s. The results of a study of a Novartis drug called pelacarsen, which has to be injected monthly, are expected in 2026.Other injectable treatments for Lp(a) in development include Silence Therapeutics' zerlasiran and Amgen's olpasiran.There’s also multiple tablets in the runningWhile these are injectable treatments, Eli Lilly is also testing a drug called muvalaplin, which is administered orally in the form of a tablet.Pharma giant Merck has signed an agreement with Chinese firm Jiangsu Hengrui Pharmaceuticals to develop, manufacture and commercialise its oral tablet to reduce Lp(a) levels. The tablet is presently being evaluated in a clinical trial in China and Merck could pay upto $2 billion for it.However, cardiologists have cautioned that despite the initial optimism there’s no guarantee the drugs will protect people unless tests confirm it. Skeptics were once enthusiastic about drugs that raised levels of HDL (high-density lipoprotein), which is popularly referred to as “good cholesterol”. It was believed this would help because people with naturally high levels of this cholesterol had lower rates of heart disease. However, trials found that the HDL-raising drugs did not help prevent heart disease.With inputs from agencies, NYT