Novartis on Wednesday won Food and Drug Administration approval for a genetic drug that can powerfully lower cholesterol with just two injections a year, one that it hopes could be widely used to lower the risk of heart disease complications.
Called Leqvio, the drug works similarly to approved cholesterol-cutting medicines from Amgen and partners Sanofi and Regeneron, and comes with similarly high sales expectations as those drugs did upon arriving on market six years ago.
All three treatments target a protein, or the genetic instructions encoding for it, that slows the removal of so-called bad cholesterol from the blood. With Leqvio's approval, each is approved for people with heart disease who can't bring their cholesterol levels down enough by using older generic drugs known as statins, or those who have genetically high amounts.
Leqvio's edge may lie in convenience. While Amgen's and Sanofi and Regeneron's drugs are typically given once or twice a month, Leqvio can be administered just twice a year after two injections in the first three months.
Novartis, which spent nearly $10 billion to buy the biotech developer of Leqvio two years ago, envisions the drug will be used in doctors' offices during regular visits, potentially helping patients stay on the drug and avoid heart complications that can become more likely if cholesterol is uncontrolled. Repatha, Amgen's drug, and Praluent, Sanofi and Regeneron's, are self-administered.
"We saw that there were extreme challenges with adherence," Victor Bulto, Novartis' head of U.S. pharmaceuticals, said of Repatha and Praluent. "We strongly believe that Leqvio, twice a year, will address the adherence challenges they had."
But the obstacles faced by Repatha and Praluent, which both disappointed commercially, involved more than just adherence. Their makers set unexpectedly high prices at launch that sparked widespread insurer resistance to covering them widely.
Moreover, long-term results from clinical trials showed the drugs didn't prevent heart attacks, strokes and deaths as well as many experts had expected based on their ability to lower cholesterol. Compared to placebo, both Repatha and Praluent reduced the risk of so-called major adverse cardiovascular events by about 15%.
With that history in mind, Bulto said Novartis has prepared for Leqvio's launch by working with 200 major U.S. health systems to identify patients who might qualify for treatment and select them based on their risk. It's similar to the "population health" approach the company has taken with the U.K.'s National Health Service, which signed a pact with Novartis to treat 300,000 people with Leqvio at a price that neither side disclosed.
Michael Sherman, the top doctor at New England-based health insurer Harvard Pilgrim Health Care, said Leqvio could help patients keep on treatment.
"People don't like self-injecting for something that doesn't have symptoms," like heart disease, Sherman said in an interview before Leqvio was approved. "Having something less frequent is game changing. I think it offers an opportunity for greater value."
Novartis priced Leqvio at $3,250 per dose for U.S. sale, meaning the first year of treatment will cost $9,750 and subsequent years $6,500. That's slightly higher than the $5,400-per-year price that the Institute for Clinical and Economic Review, a watchdog group on drug costs, said would be cost effective for Leqvio when used broadly, but lower than the $10,000 estimate for patients with rarer, genetically driven high cholesterol.
Novartis plans to work with heart doctors to ensure they are comfortable seeking reimbursement from Medicare, which will cover many of the patients needing Leqvio, Bulto said. As an in-office procedure, Leqvio injections will be covered under the program's Part B, which requires physicians to buy a product and then bill Medicare after it's used. Cardiologists, who typically prescribe self-administered drugs, are less familiar with the Medicare procedures than cancer doctors, who are accustomed to giving patients injectable drugs like chemotherapy, Bulto said.
But coverage through Part B could also be an advantage for Leqvio over Repatha and Praluent. Physicians will be reimbursed for Leqvio at the average amount paid by physicians plus a 6% add-on fee, and Medicare doesn't have much power over price. The other two drugs are covered by Part D, which involves private health insurance plans that can negotiate prices with drugmakers somewhat.
Leqvio could eventually become a home-delivered subcutaneous shot and therefore fall under Part D "down the road," Bulto acknowledged. But "the clinical trials were conducted exclusively with [healthcare provider] administration," he said. "We want this administered by [a healthcare provider] even if it's a simple subcutaenous injection."
Novartis could also face physician concerns around the drug's safety. Unlike Repatha and Praluent, both biologic drugs that have been around for years, Leqvio is a type of genetic medicine that so far has only been used in rare diseases. (Leqvio, which interferes with RNA messages that cells use to build proteins, was invented by Alnylam Pharmaceuticals before being licensed to The Medicines Co., which Novartis bought in 2019.)
Since Leqvio doesn't have a long safety record, some doctors may be reluctant to choose it over its competitors because patients could end up taking the drug for years.
"The question is going to be always in terms of long-term safety, and the answer is we don't know about that yet," University of Virginia cardiologist Eric Rembold said. "That's going to be harder to sell to people, even if it may be more convenient."
The British Medical Association and the Royal College of General Practitioners made a similar point on the U.K.'s plans for Leqvio. Due to the comparative lack of long-term safety and outcomes data, the two groups recently urged use of more well-tested strategies like lifestyle changes, statins and Repatha or Praluent before Leqvio.
"I think what it's going to probably need is a long-term trial like the statin trials or the [Repatha and Praluent] trials," Rembold said. "I would want to see a randomized trial of nothing versus this drug and follow people for at least five years," he said.
Novartis is currently conducting a trial to assess Leqvio's effect on heart-related health events like heart attacks and strokes.
Leqvio's OK comes a year later than Novartis had originally sought, after the FDA declined to approve the drug as its inspectors were unable to visit Novartis' manufacturing plants due to pandemic travel restrictions.