Analysts recently applauded promising clinical trial results for two late-stage cardiovascular drugs but commercial success for the therapies, if approved, will likely be challenging, given the recent access challenges faced by novel heart drugs like Novartis’ Entresto and Amgen’s Repatha.

Novartis said in June that its experimental canakinumab, already approved as Ilaris for juvenile arthritis, met its endpoints in late-stage clinical trial, reducing major cardiovascular events like heart attack and stroke. Analysts said then that this data indicates that the drug could change how heart disease is treated because it targets inflammation in the heart, taking a new mechanism of action in a disease that represents one out of every four deaths in the U.S.

Similarly, new clinical data for Merck’s anacetrapib, a CETP inhibitor, showed the potential to raise good cholesterol and lower bad cholesterol simultaneously.

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But, drugmakers are finding that hitting endpoints in clinical trials may no longer enough be enough to sway payers to cover new drugs. Commercial insurers and pharmacy benefit managers have increasingly placed restrictions like prior authorization on new drugs, driven by concerns about their high price tags. At the American College of Cardiology’s annual meeting in March in Washington D.C., Credit Suisse analyst Vamil Divan said one of the key themes to emerge was “how challenging it is to navigate the reimbursement process for treaters.”

This was evident in the recent launches of of Novartis’ heart-failure pill Entresto and Amgen’s cholesterol-lowering injection Repatha, two heart drugs that experts believed could change the treatment paradigm for patients intolerant to statins and those with heart failure. They were forecast to sell in the billions annually. But, the drugs have yet to come close to their forecasted sales: in 2016, Repatha saw sales of $101 million, while Entresto brought in $68 million.

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In 2016 if you were a patient with commercial insurance looking to fill a new prescription for a PCSK9 inhibitor like Repatha, the initial attempt to fill the drug was approved just 11.6% of the time, according to a study conducted by Symphony Health Solutions in February. Entresto, too, has been beset by restricted formulary access. Novartis executives have cited prior authorization as a factor in Entresto’s slower-than-expected sales uptick.

Novartis has told investors that adoption of Entresto among cardiologists has been slow because these physicians don’t traditionally advocate for new drugs to insurers, compared to other specialists, like oncologists. In 2015, David Epstein, then the Novartis Pharmaceuticals division head, said that “cardiologists haven’t had to spend the time and build the office staff” necessary to advocate for insurers to cover a new drug.

Merck and Novartis both declined to comment for this story.

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There are a number of reasons why new cardiovascular drugs have had trouble gaining traction in the U.S. market, and commercial payers are a primary reason why the drugs haven’t realized those sales forecasts.

“It’s a question we’re all struggling with,” said Craig Granowitz, chief medical officer for Amarin, which markets Vascepa, a fish oil pill that treats patients with high levels of triglycerides.

Often in the practice of cardiology, you’re “talking about chronic care with no easy endpoints to measure, no surrogates to measure, and the therapy goes on ad infinitum,” Granowitz said.

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Drugmakers need to proactively share information with payers about what patients should be taking a drug — even if doing so may put them at risk of narrowing a product’s use to a smaller population, said Kelly Wilder, EVP, managing partner for Precision for Value.

“It’s a hard conversation to have,” Wilder said. “No one wants to be niche. You want the broadest access and to leave that decision to clinicians.”

Another common refrain from industry on how it’s working to address questions about access is by engaging in value-based agreements — contracts that require drugmakers to share the financial risk of new and often expensive products with payers by promising that their therapies actually improve outcomes for patients. One of the biggest issues in forming the contracts is deciding on metrics that both drugmakers and payers agree is important and clinically beneficial for the patient.

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Granowitz said these partnerships aren’t the easy answers they’re often purported to be. “The devil is in the details,” he said. “The issue is no one really wants to bare the risk with a value-based agreement. Everyone wants someone else to hold the bag. ”

Still, some drugmakers aren’t doing enough with the insurance coverage they’ve already secured, Wilder said.

“There’s this blanket notion of ‘access,’” she said. “Access is local — it’s with your doctor based on your specific benefits with the employer. There’s little awareness when the patient gets to the healthcare provider. Manufacturers have all their organizations to pull it through at the national or regional level but the challenge is how they’re doing it on the local level.”