Just over 30 percent of patients who receive a pricey prescription for the cholesterol-lowering medications known as PCSK9 inhibitors (PCSK9i) are able to pay for the drugs, new research states.

According to a JAMA: Cardiology investigation of more than 45,000 patients who were prescribed PCSK9i between August 2015 and July 2016, under half received insurance approval for the medications.

PCSK9i drugs alirocumab and evolocumab were approved in 2015 for patients struggling with high cholesterol, the study stated, and can cost more than $14,000 a year at retail value.

Lead author of the study Ann Marie Navar, MD, PhD, worked with a team of researchers to sift through the pharmacy transaction data of 45,029 American patients who were prescribed PCSK9i to treat their genetically high cholesterol or consistently high low-density lipoprotein (LDL) levels. The majority of subjects—56.6 percent—were 65 years old or older at the time of the study, and just more than half were women. The team used a handful of variables to assess approval or abandonment of prescriptions, including out-of-pocket copays, clinical diagnoses, LDL cholesterol levels, prescriber specialties and pharmacy benefit managers.

Navar and colleagues found that of patients who received a prescription for PCSK9i, 20.8 percent received approval on the first day, and just 47.2 percent ever received approval. Of the approved patients, 65.3 percent had their prescriptions filled, meaning only 30.9 percent of all patients recommended for PCSK9i therapy actually received it.

After adjusting for several demographic factors, the scientists discovered older patients, those with atherosclerotic cardiovascular disease and men were most likely to be approved for PCSK9i, while LDL cholesterol levels and statin use didn’t seem to have any effect on approval rates. The authors also wrote the odds of being approved for the medication were influenced by whether a patient had commercial or governmental insurance—52.5 percent had federal coverage—and whether a patient used a speciality or retail pharmacy, with approval rates varying three-fold among the 10 biggest pharmacy benefit managers.

More than 75 percent of patients abandoned their prescriptions due to copayments of $350 or more, according to the study, compared to just 7.5 percent with no copay. Navar and her team wrote this was the most telling variable of all, noting that a third of approved prescriptions that weren’t filled “owing to copay.”

Another JAMA: Cardiology study released in mid-September nodded to the effectiveness of PCSK9i for the nine million U.S. adults struggling with atherosclerotic cardiovascular disease, but also acknowledged the high price tag on the medication.

“Understanding patients’ share of drug costs is important because high out-of-pocket costs can adversely affect affordability and adherence to lifelong treatment,” Dhruv S. Kazi, MD, and co-authors wrote, noting that while nine in 10 Medicare Part D plans cover the PCSK9i, copays can still exceed $300 per month, or projected annual costs of nearly $5,000.

Daniel B. Mark, MD, MPH, and Kevin A. Schulman, MD, MBA, noted in a JAMA opinion piece that the concerns about PCSK9i, which is still a relatively new drug to the field, don’t revolve around safety or efficacy. It’s all about the price.

“The conflict between wanting to provide potentially beneficial innovations to patients and being unable to provide those innovations due to cost and affordability is not a new problem in medicine,” the doctors wrote. “Neither physicians nor patients have sufficient policy influence to alter the way these access or investment decisions are made. Congress has the power to make changes but not the will. Payers are thus put in the unenviable position of being forced to make life-altering decisions for their health plan members on financial grounds.”

Mark and Schulman said this is a risky place to be, since cases like that of PCSK9i are becoming increasingly common, potentially numbing policy makers, payers and clinicians to the financial difficulties associated with these medications.

“Painful as it is, draconian restrictions on access to drugs that are priced for profit maximization out of proportion to any value proposition and budget tolerances may continue to be the only way medicine can send a strong signal to innovators that their future rewards are tied not just to scientific advancement but also to affordability,” they wrote. “Profit maximation behavior in medicine out of proportion to value provided is widespread. Ultimately, this message will need to be heeded by the entire healthcare enterprise.”