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cholesterol-cutting drug from Amgen succeeded in lowering patients’ risk of cardiovascular trouble in a huge clinical trial — but the results, announced Friday, may not be good enough to prompt insurers to cover the expensive drug for millions of patients.

Amgen’s treatment, called Repatha, met its goals in a two-year trial on more than 27,000 patients with heart disease who were already taking a maximum dose of statins like Lipitor and yet still had stubbornly high cholesterol. Those who got Amgen’s drug were 15 percent less likely to suffer a bad outcome, defined as heart attack, stroke, hospitalization for chest pain, placement of a stent, or death.

However, looking at death rates alone, there was no significant difference between the two groups.

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Cardiologists said the result is profound, but it will likely be a disappointment to investors, who widely expected Repatha to cut that bundle of cardiovascular problems by 20 percent.

Amgen’s stock fell about 7 percent after the data became public.

It remains to be seen how the trial results will affect Amgen’s contentious discussion with payers and pharmacy benefit managers, who have balked at the drug’s roughly $14,000-a-year list price.

Before the new data came out — when the drug was known to reduce cholesterol, but when it wasn’t clear it could reduce hospitalizations — insurers and benefit managers rejected more than three-fourths of prescriptions that physicians wrote for Repatha. The question now is whether the new data will persuade them the drug is worth covering.

“We think we’re really at the beginning of a new era in how to further treat cardiovascular patients,” said Dr. Jeffrey Kuvin, a cardiologist at Dartmouth-Hitchcock not involved in the Amgen study. “The real test now will be how we can actually implement this science into daily practice.”

A money-back guarantee

Repatha, like a rival drug from Sanofi and Regeneron, is approved to lower LDL, or “bad,” cholesterol by blocking a bodily protein called PCSK9. The new class of treatment arrived on the market about a year and a half ago with blockbuster sales projections; Amgen was expected to ring up annual sales of around $3 billion. But a combination of unconvinced physicians, wary payers, and pugilistic pharmacy benefit managers has limited revenue to but a fraction of that figure.

Amgen says its latest data, presented at the American College of Cardiology Conference, firmly answers the question of whether dramatically lowering LDL can improve patients’ lives — more than what’s been possible with inexpensive statins. And the company believes Repatha’s performance more than justifies expanded use of the drug.

“The barriers that have been thrown up by the payers have been around, ‘You don’t have outcomes data,’” said Dr. Sean Harper, Amgen’s head of R&D. “Well, that’s off the table.”

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The company hopes to persuade insurers to cover it in part by offering a sort of money-back guarantee: Amgen will refund the cost of Repatha if patients suffer a heart attack or stroke while taking the drug, said Dr. Joshua Ofman, Amgen’s senior vice president of value, access, and policy.

“We want to put our money where our mouth is,” Ofman said. “We stand by our product, and we’re willing to take risks around outcomes.”

Repatha’s $14,000 price tag is the list price. It doesn’t account for the customary discounts and rebates offered to payers, which average around 30 percent across the industry, Harper said. In pure dollar terms, he argued, Repatha’s ability to reduce patients’ risk of costly hospitalization more than justifies its price.

But the industry’s gatekeepers may not agree. In a survey of payers conducted by analysts at Leerink, about half of the respondents said they expected to approve more PCSK9 prescriptions if Amgen’s study was a success, but they expected a median improvement of 20 percent on the trial’s primary endpoint, well above the 15 percent Amgen demonstrated.

Express Scripts, the nation’s largest PBM, is now preparing for spike in Repatha prescriptions. The company has streamlined its process for reviewing scripts, Chief Medical Officer Dr. Steve Miller said, but Amgen’s data — and its offer of a refund program — haven’t changed Express Script’s concerns about Repatha’s price tag.

“These are incremental gains in the right direction, and it’s an improvement for patients,” Miller said. “The big question is going to be, at $14,000, is the improvement enough?”

Repatha’s numbers look better in the trial’s secondary endpoint, which looks at data from the same patients, but leaves out two adverse outcomes: hospitalization for chest pain and stenting. By that measure, Repatha led to a 20 percent risk reduction for heart attack, stroke, and death.

But looking at death alone, Repatha had no effect, and it wasn’t meaningfully better than placebo at keeping patients out of the hospital with chest pains.

On the safety side, Amgen spotted no new risks of taking the drug.

A chilling effect on further research?

If Amgen’s data don’t move the needle and Repatha remains a blockbuster interrupted, there could be a chilling effect on cardiovascular R&D in the drug industry. The Medicines Company, Esperion Therapeutics, and others are spending millions of dollars to prove their drugs can safely lower LDL levels. But as the bar for profitability gets higher and higher, the odds of recouping such investments only lengthen.

“As a former colleague of mine, Jack Scannell, once called it, this is the ‘better than the Beatles’ problem,” said Geoffrey Porges, a biotech analyst at Leerink.

“The challenge for this industry is if the predecessor medicines are really good, and are now available for pennies, and are ubiquitous, it’s really hard to come up with something that has sufficient incremental benefit and appeal to justify a price that is hundreds of times higher,” Porges said.

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Amgen has long complained that insurers are rejecting prescriptions for Repatha for no rhyme or reason, and there’s some evidence now to back that up.

A study to be presented at the cardiology conference on Saturday looked at more than 44,000 PCSK9 prescriptions over the course of a year and found no major differences between the 83 percent of patients who got rejected and the 17 percent who were approved.

“The experience is frustrating,” Kuvin said. Doctors have to submit pages of documentation to prove that patients’ high cholesterol has persisted despite two rounds of statin therapy, or that they have an inherited disorder that leads to dangerously high LDL levels.

“Now, with strong outcomes data, I’m hopeful that the marketplace will appreciate these data and allow practitioners to prescribe these drugs in an economically favorable way,” Kuvin said.

A bitter patent fight continues

Meanwhile, the famously litigious Amgen is fighting in court with its sole PCSK9 rival.

In January, a federal judge ruled that Sanofi and Regeneron’s treatment, Praluent, infringed Amgen’s patents. The judge took the unexpected step of barring the drug from the market. Sanofi and Regeneron got a stay on that ruling and are now in the midst of an appeals process that analysts believe will end with a settlement between the parties.

Regardless of the legal dispute, Amgen maintains that it is the clear leader in the field. And Harper doesn’t think Repatha’s outcomes data should be seen as a boon to the whole class of medicines — just Amgen’s.

“People would like to make that kind of simplified assessment, but look at what happened with the Pfizer molecule,” Harper said, referring to an erstwhile PCSK9 competitor that dropped out of development when investigators found that patients’ bodies were rebelling against the drug. “You could go ask Pfizer that question,” he added.

Correction: A previous version of this  story misstated the professional affiliation of Dr. Jeffrey Kuvin.

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