This week's announcement comes after cardiologists have spent several years sharing accounts of their difficulty gaining access to PCSK9 inhibitors for their patients.
On Tuesday, Sanofi and Regeneron announced that the original $14,000 annual cost of the cholesterol drug alirocumab (Praluent) would drop up to 75% for patients who obtain it through Express Scripts, under a deal that makes alirocumab the exclusive proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor on its National Preferred Formulary. The agreement takes effect July 1, 2018.
The announcement came nearly 3 years after alirocumab and its competitor, Amgen’s evolocumab (Repatha), were approved a month apart with high expectations from analysts and cardiologists alike. In clinical trials, these injectable drugs had reduced low-density lipoprotein (LDL) cholesterol up to 60%. But payers and pharmacy benefit managers (PBMs) like Express Scripts warned at the outset that they would erect barriers for PCSK9 inhibitors, and they did.
For perspective on what the deal tells us, The American Journal of Managed Care® spoke with Michael D. Shapiro, DO, FACC, who is an associate professor of Medicine and Radiology at the Knight Cardiovascular Institute, Oregon Health & Science University (OHSU).
Shapiro said when PCSK9 inhibitors were first approved, he and his colleagues shared the excitement that the therapies would offer a new tool in prevention of cardiovascular disease (CVD). However, as they tried to prescribe them, “We were met with barriers to access as everyone else.”
1. The agreement will ease the approval process for doctors.
Cardiologists who prescribe PCSK9 inhibitors say the first attempt to get payer approval almost always fails. Payers ask for lab reports and lengthy documentation of prior drug history—including material that some patients can no longer obtain. Tuesday’s announcement calls for doctors to sign a simple attestation that the patient meets FDA criteria and has a history of being unable to reach safe LDL cholesterol levels even when taking maximally tolerated statins. (Although payer criteria vary, Express Scripts’ criteria for atherosclerotic CVD will be ≥70 mg/dL or ≥100 mg/dL for heterozygous familial hypercholesterolemia).
At OHSU, Shapiro said, the barriers caused his institution to set up a special PCSK9 inhibitor clinic. “The creation and implementation of a PCSK9 inhibitor clinic has transformed a formidable challenge into an opportunity for process and quality improvement and added value to our program,” he said. “We have surmounted those barriers and have a near 100% rate of approval."
However, he said, “We are fortunate that we can devote the resources to a process that lets our institution have that high approval rate.” A community clinic would have a hard time devoting the staff time to the process.
2. A portion of the manufacturer’s rebate will go straight to the consumer.
The shift in the use of manufacturer rebates—from a tool to lower overall premiums to a way to bring discounts to the consumers most affected by high drug prices—comes as both members of Congress and FDA Commissioner Scott Gottlieb, MD, are drawing attention to rebates as a problematic and mysterious piece of drug pricing. Rebates are the focus of a class action lawsuit involving the 3 largest insulin manufacturers, including Sanofi.
At the clinic level, doctors may select alirocumab more frequently if it’s cheaper and easier for patients to get. Shapiro said that most physicians view the 2 antibodies as having similar efficacy. “We always go with the antibody that is more accessible to the patient,” he said. “With that in mind, this represents a major advance.”
3. The announcement is a win for the Institute for Clinical and Economic Review (ICER).
Tuesday’s deal grew out of ICER’s cost-effectiveness analysis of alirocumab, which was done quietly in advance of the March announcement of the ODYSSEY Outcomes trial. Those results showed that the drug offered a 15% overall reduction in cardiovascular events, including a 29% reduction for those with the LDL cholesterol levels, as well as mortality benefits. ICER crafted the value benchmarks that formed the basis of the Express Scripts deal: price ranges of $4500 to $8000 for most patients.
ICER said the deal represents a shift: “Following a decades-long trend toward dysfunction and finger-pointing, the US healthcare system is beginning to address its drug pricing problem through the emergence of a ‘grand bargain.’ When a manufacturer is willing to responsibly price an innovative medicine in line with its clinical benefits, payers should reciprocate by removing the hurdles that can prevent patients from getting the drug,” the group said. “As the nation strives to help all Americans achieve sustainable access to high-value care, this sort of grand bargain—a win-win-win for manufacturers, payers, and patients—is a model for the rest of the industry to contemplate.”
4. The deal shows doctors’ headaches were about PCSK9 prices.
Shapiro has never heard of the use of an “attestation” for another cardiovascular therapy. When asked if the alirocumab agreement is, essentially, an acknowledgment that the barriers that doctors and patients have experienced were really about price and not about whether the drugs were clinically appropriate, he said that was likely true. But he acknowledged that the issue of access is complex. When drugs reach the market at extraordinarily high prices—like those seen for PCSK9 inhibitors—payers have found ways to restrict access to them.
“The fact that they liberalize access as soon as the cost comes down clearly shows the reason they had the barriers up in the first place,” Shapiro said. “The real question is who should be making this judgment?”
5. Express Scripts’ Miller: Other payers must buy in.
As big as Express Scripts is, the PBM can’t determine on its own if the alirocumab deal will break the logjam with PCKS9 inhibitors. It directly controls prescriptions for 25 million customers and manages them for another 58 million through contracts with payers and employers. To some analysts, Regeneron’s position is a capitulation, but Chief Medical Officer Steve Miller told Forbes that it’s about fairness—and that its clients and other giant PBMs must now embrace the idea of awarding market access in exchange for fair prices. Said Miller: “I really hope this works because otherwise it's a bad message for everyone going forward.”