Seth Martin's advanced lipids clinic at Johns Hopkins Medicine treats some of the sickest heart-disease patients around. But two doctors, two nurses and another staffer there are devoting much of their time to fighting with insurance companies over two advanced cholesterol drugs.
Nearly 90 percent of the patients Hopkins wants to put on expensive, powerful PCSK9 inhibitors are initially rejected, making heart disease perhaps the central stage in the battle over high U.S. drug prices. In the least, it's the drug-pricing battle that may matter to the most Americans: Heart disease is the No. 1 cause of death in the country.
Two years after PCSK9 inhibitors from and - hit the market, patients are caught in the middle. The injectable drugs — which block a liver protein that prevents the organ from breaking down cholesterol — reduce bad cholesterol as much as 60 percent when combined with statins that have dominated cholesterol-reduction treatment for years. And they work for patients who get poor results from statins or can't take them because of side effects, Martin said.
He added, "Most patients are rejected even when they clearly meet the criteria. There's a process in place to make this as challenging as possible."
That's because the drugs also cost many times what statins do. Generic versions of familiar drugs, like Pfizer's Lipitor, can be had for as little as $10 a month, compared to about $1,200 for Amgen's Repatha or Sanofi's Praluent. Statins are so cost-effective that some insurance carriers even waive co-payments to make sure patients take them.
That means the fight is over which patients should get which drugs, a debate patients join when making decisions for themselves. Two studies published in the last month will fuel even more arguments; they reached starkly different conclusions about whether Repatha and Praluent are worth the money. The latest results come against a backdrop of weak sales for the drugs. Amgen said insurers have approved just 44,000 U.S. patients for Repatha.
"It was developed for patients who are on the very best therapy but haven't been able to drive their bad cholesterol lower," said Joshua Ofman, senior vice president for global value, access and policy at Amgen. "Some of the controversy is because people don't understand that this drug is intended to be used by patients who are already on a statin.''
Most people with high cholesterol do fine with statin treatment, Ofman said. Those drugs, whose sales peaked at nearly $40 billion but have been battered by generic competition since 2012, are effective in most patients and have few side effects in about 90 percent of cases. In the rest, the most common side effect is muscle pain, which can be severe enough to make patients seek alternatives.
The patients who need more are tougher cases, many suffering from a genetic condition called familial hypercholesterolemia, or FH, which affects 1.3 million Americans. Patients who have the FH gene can develop heart disease as early as childhood, and many can't get their cholesterol down to normal levels even with statins and a rigorous diet. Patients who have previously had a heart attack or stroke or are at risk of limb amputations because of poor circulation are also prime candidates for the more expensive drugs.
"This is absolutely an adjunctive therapy for statins, not a replacement," Martin said. "We don't just skip the statins and go straight to the [expensive] stuff."
The problem has been convincing payers that the new drugs are worth the money. Insurers initially turned down as many as 80 percent of patients who were prescribed Amgen's Repatha, Ofman said, though the numbers are improving slightly after a clinical study released in New England Journal of Medicine in March showed the drug did reduce hospitalizations for heart attacks and strokes but did not reduce mortality from heart disease. The most recent data show 71 percent of prescriptions are initially refused — with no clinical differences among the cases approved and rejected, Ofman said.
"Physicians have to fight very hard to get the drug even for the most high-risk patients," he said. "But doctors say most patients who are clear candidates for Repatha or Praluent can get their prescriptions approved eventually, if they appeal the insurance denial with their doctor's assistance.''
Payers say they will pay for PCSK9 inhibitors, but only for patients who really need them. CVS Caremark — one of the two giant pharmacy-benefit managers along with Express Scripts, who help set the tone for other U.S. payers — didn't respond to requests for comment. It has warned that drugs like Repatha could cost the U.S. health-care system $200 billion.
"We've worked to make sure that the right patients get access to a drug they need," Express Scripts spokesman Brian Henry said in an email. "When the PCSK9 drugs first came to the market, we saw a lot of prescribing for patients who were not indicated for the drug. With additional education, that has lessened."
But even in more conventional doctors' offices than Hopkins' clinic, the new drugs are hard to get, according to the heads of cardiology at the two largest non-hospital-based medical practices in metro New York.
"It's very hard to get people on the drugs, period,'' said Andrew Beamer, chair of cardiology at Berkeley Heights, N.J.-based Summit Medical Group. "There is a risk in the prior authorization not only when you prescribe but also when you renew. They've done such a good job of making it expensive to ask that I don't even try to put people on. It's like self-censorship.''
Most patients will respond to statins, either alone or in tandem with Merck's Zetia, which goes for about $160 a month before discounts, Beamer said. But his practice has about seven patients on PCSK9 inhibitors. At 550-doctor CareMount Medical in Mount Kisco, N.Y., about three patients take the drugs, said director of cardiology Richard Keating.
"They're not the most common drugs we use," Keating said. "But they work very well, and the side-effect profile is quite benign.''
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The real dispute is over whether the PCSK9 inhibitors deliver enough bang to be worth the bucks. That was the subject of two competing studies that hit medical journals in August.
PCSK9 inhibitors reduce cholesterol but haven't been shown to reduce mortality, said Dhruv Kazi, associate professor at University of California San Francisco's medical school. Using estimates of how many deaths might be avoided, as well as an assumption that every extra year lived with a good quality of life is worth $100,000, he argues that the drugs are only worth about $4,200, based on findings published last month. Without assuming any improvement in mortality, he argues that the drugs are worth about $2,000 per year.
The lifetime bill for these drugs could be higher for many patients than even the one-time, $95,000 Hepatitis C treatments that have galvanized debate over drug prices. "Reducing the price of PCSK9 inhibitors remains the best approach to delivering the potential health benefits of PCSK9 inhibitors therapy at an acceptable cost," Kazi and colleagues wrote.
The other study, supported by Amgen, estimated the value of Repatha at $9,669 per year — less than its list price but consistent with prices paid after common discounts. To get there, researchers valued each quality-adjusted life year at $150,000 and assumed a higher rate of avoided heart attacks than in Kazi's study.
"That drives the majority of the difference," Ofman said.
What should patients make of this?
Most people with cholesterol high enough to need treatment should stick with statins, doctors largely agree. Higher-risk patients should ask about newer treatments. For now.
The wild card is whether cholesterol guidelines might move lower in the future, based on emerging research that indicates the inhibitors like Repatha can lower the buildup of cholesterol plaques in the coronary artery walls to levels not possible with statins alone, Beamer said. Price cuts for PCSK9 inhibitors and falling tolerance for cholesterol might be the keys to a big market in the future, Beamer argued.
"If the guidelines change, price cuts might expand the market," he said.
— By Tim Mullaney, special to CNBC