Patrice Wendling

March 21, 2017

WASHINGTON, DC — New research suggests that in the first year after gaining US approval, more than half of prescriptions for the PCSK9 inhibitors alirocumab (Praluent, Sanofi/Regeneron) and evolocumab (Repatha, Amgen) were rejected and one in three were never picked up from the pharmacy[1].

"Instead of physicians accepting that it's a gamble to get patients on it, I think when we're talking about maximizing the effectiveness of PCSK9 therapies—in addition to all the things that are brought up around the FOURIER trial and who we should be giving them to and how long people should be on therapy—we need to be thinking about how we actually get the drug to the patient," Dr Ann Marie Navar (Duke Clinical Research Institute, Durham, NC) told heartwire from Medscape after her presentation at the American College of Cardiology (ACC) 2017 Scientific Sessions.

She said physicians are struggling with how to balance getting their patients on the therapies they need with how many resources they have in house. A recent study estimated provider practices are spending 20 hours a week on prior authorizations.

Dr Ann Marie Navar

"As a cardiologist, it took me hours and hours and hours to try to get my first patient a PCSK9 inhibitor, and I still haven't succeeded for that particular patient, and it's really frustrating," she said.

Commenting to heartwire , panelist Dr Mariell Jessup (Leducq Foundation, Boston, MA) said, "The emperor has no clothes; we have all these drugs and nobody is getting them. Do you know what that does to physician fatigue to get that all done? I've talked to people that have written letter after letter after letter. It's unbelievable."

To determine whether this experience is happening nationwide, Navar and colleagues examined first PCSK9 prescriptions in 45,029 patients (median age 66 years; 51% female) between August 1, 2015 and July 31, 2016 in the Symphony Health Solutions database, which covers 90% of retail, 70% of specialty, and 60% of mail-order pharmacies in the US.

Nearly half (48%) of prescribers were cardiologists, and 37% were general practitioners. Most patients (52%) had government insurance, typically Medicare, and 40% had commercial insurance.

In the first 24 hours after being submitted to the pharmacy, 79.2% of prescriptions were rejected. Ultimately, 52.8% of all PCSK9 prescriptions were rejected.

Of special note, 34.7% of prescriptions for the pricy lipid-lowering drugs were abandoned at the pharmacy.

"I think that's been the clinical experience with sacubitril/valsartan [Entresto, Novartis]; it's the same problem that people find out how much it's going to cost and they don't pick up their prescription. I think it's a huge problem," Jessup told heartwire.

Only 9.8% of patients participated in a coupon program to reduce PCSK9 costs, but when they did they were 17-fold more likely to receive their therapy.

In multivariate adjusted analysis, predictors of receiving PCSK9 therapy were use of a mail-order pharmacy (odds ratio 4.4; 95% CI 3.3–5.9), commercial health insurance (OR 4.4; 95% CI 4.0–4.8), and prescription by a cardiologist (OR 1.6; 95% CI 1.5–1.7).

The median time to dispensing was 9.9 days but exceeded a month for more than 25% of patients.

"The amount of time that it takes from the first prescription being written for a patient and the drug getting into the hand of the patient has potential to affect patient self-efficacy and patient adherence, as well as patient willingness to even initiate therapy once they receive the drug in hand," Navar told the rapt audience.

The most surprising finding, she told heartwire , "was how much rates varied, even within commercial payers; it was remarkable to me, and I think what it speaks to is that every different payer or [pharmacy benefit manager] PBM comes up with their own criteria, and the variability in those criteria is translating into variability in rejection rates."

Rejection rates ranged from 33.2% to 77.6% across commercial payers, 37.9%% to 83.5% across government insurance programs, and 33.1% to 74.7% across PBMs.

Variability by payer and lack of improvement over the study period suggest not all rejects are due to clinical factors, Navar said. Whether having long-awaited clinical outcomes data from FOURIER will change rejection rates is unclear.

Some physician practices have taken to hiring dedicated staff to increase PCSK9 precertifications, but Navar told heartwire that's not the way forward.

"Right now, smaller practices or lower-volume practices may have the ability to do that, but what we're talking about is a class of therapy that is potentially going to be used in very large numbers of patients; so depending on the boutique lipid clinics or the individual cardiologist who is a specialist in lipids to have to be the gatekeeper for PCSK9 inhibitors for everyone is just not a realistic plan," she said.

Still others have turned to sites like that aggregate much of the necessary paperwork, but "that's sort of a Band-Aid to a gaping wound," said Navar.

Jessup agreed with Navar's call for a more unified approach to the approval process and learning from the experiences of disciplines like oncology and rheumatology that have struggled for years with patient access to costly medications.

"In cancer, they get a short-term drug, but with these drugs the patients are on them forever," Jessup told heartwire . "I think we do have to have a template, there needs to be a standardized template to do these precerts."

The study was funded by Amgen. Navar reported research support to her institution from Amgen and Sanofi Regeneron; consulting for Sanofi; and a research grant from National Heart, Lung, and Blood Institute. Jessup reported salary from the Leducq Foundation.

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