Putting an End to Heart Attacks by Editing Human DNA
Verve Therapeutics is targeting cholesterol-causing genes to clear arteries with its experimental therapy.
By Angelica Peebles
May 6, 2022, 5:00 PM GMT+7
Even after decades of drug breakthroughs aimed at preventing heart attacks, they remain the world’s leading cause of death. The pills and injections on the market do the job of lowering the cholesterol that clogs blood vessels and puts people at risk of a heart attack. But not everyone has access to them, and some won’t stick to treatment plans that can last the rest of their lives. Verve Therapeutics Inc. is proposing a radical solution: altering a person’s genome—the body’s instruction manual—to stop the buildup of bad cholesterol. “We’re on the cusp of potentially transforming that model to a one-and-done treatment,” says Sekar Kathiresan, chief executive officer of the Cambridge, Mass.-based company.
Verve plans to initially target those who’ve already had a heart attack because of extremely high cholesterol caused by a hereditary condition known as familial hypercholesterolemia, which affects 31 million people globally. If it works to reduce low-density lipoprotein (LDL), or “bad,” cholesterol in that group, the company would look to widen the treatment pool, eventually aiming to give it to young people as a preventive measure, though it’s too early to say when that could happen.
The company is backed by Google Ventures (now known as GV) and prominent biotech investors Arch Venture Partners and F-Prime Capital. It went public in June, reaching a market capitalization of $2.89 billion that month. (Its value has since dropped to about $700 million, falling along with the rest of the biotech sector.)
Kathiresan helped found Verve when he was an acclaimed cardiologist and geneticist at Harvard, where he discovered genetic mutations that caused people to have low levels of cholesterol, offering them protection from heart attacks. Now he’s trying to replicate that phenomenon by turning off cholesterol-raising genes. Verve is developing medicines focused on two genes. The first treatment will go after PCSK9; the second will be directed at ANGPTL3. Some patients will need only one of the drugs; others will need both. The company uses the Crispr DNA-editing tool to change a single letter of a person’s genome. A lipid nanoparticle encases the editing system to protect it on its journey to the liver, where it turns off the desired gene.
The treatment showed encouraging signs in monkeys, cutting bad cholesterol levels by 59% after two weeks and sustaining the effect six months later. Verve is set to begin testing in humans within months; it will then be years before it has enough evidence of the drug’s safety and efficacy to consider seeking approval from regulators.
Verve will face plenty of hurdles in its attempt to treat the masses. It’s one of the first tests of using Crispr to edit DNA inside the human body, and patients and doctors could be wary of making a permanent change without knowing much about long-term safety, says Elizabeth McNally, director of the Center for Genetic Medicine at the Northwestern University Feinberg School of Medicine. Reluctance to take Covid-19 vaccines suggests some people may be loath to alter their DNA, she says.
Even if Verve can prove the drug is safe and effective at slashing levels of bad cholesterol in humans, it will then need to convince insurers it’s worth covering when it will almost certainly be more expensive than other available options, says Michael Sherman, chief medical officer at Point32Health Inc., a health insurance company based in Canton, Mass. “There has to be a reason to do the gene therapy to allow it, as opposed to it’s just newer and cooler,” he says.
Statins, the pills that became available some 35 years ago to reduce cholesterol, now cost as little as $9 for a month’s supply. The self-injectable medicines that emerged a few years ago, known as PCSK9 inhibitors—while better at lowering cholesterol than statins and requiring administration only every few weeks—haven’t reached many patients in part because they cost thousands of dollars a year. Amgen Inc. and Regeneron Pharmaceuticals Inc., the makers of the injections, haven’t been able to sway insurers even when targeting the highest-risk people with familial hypercholesterolemia, despite cutting prices by more than half, to $6,000 a year. Also, some people are wary of administering self-injections.
So far, analysts forecast that Verve’s therapy will cost from $50,000 to $200,000 per patient. Companies rarely reveal much about pricing before their products hit the market, but Kathiresan says the estimated range is “a reasonable starting point.”
Kathiresan says millions of people don’t take advantage of existing treatments and an infusion given to a young person could fundamentally alter their risk for the rest of their lives. It’s something that might have helped his own brother, who unexpectedly died of a heart attack at age 42. “What excites me is this is the answer to heart attack,” Kathiresan says. “If it works.”