Express Scripts: 'We Will Pay for Alirocumab and Evolocumab'

October 08, 2015

NEW YORK — Express Scripts, a large pharmacy benefits manager in the US, said earlier this week it will pay for both the new proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors[1].

At present, evolocumab (Repatha, Amgen) and alirocumab (Praluent, Sanofi/Regeneron), both of which were approved by the US Food and Drug Administration this summer, cost $14,100 and $14,600, respectively, for a yearlong supply of the LDL-cholesterol–lowering medication.

Alirocumab and evolocumab are fully humanized monoclonal antibodies that work by inactivating PCSK9, a protein responsible for LDL-receptor degradation. By blocking PCSK9, there is an increase in the number of LDL receptors available on the surface of the liver, and this leads to lower LDL-cholesterol levels.

While the agents are very effective and can be injected once every 2 or 4 weeks, which should aid in adherence, their cost has always been a major stumbling block. At this stage, statins are largely generic—only rosuvastatin (Crestor, AstraZeneca) remains on patent—and inexpensive.

In a perspective published October 7, 2015 in the New England Journal of Medicine, Dr Kevin Schulman (Duke Clinical Research Institute, Durham, NC) and colleagues write that the broad indication for which alirocumab and evolocumab were approved set the practice of cardiology on a collision course with specialty pharmaceutical pricing models previously reserved for drugs benefiting much smaller patient populations[2].

Express Scripts, which manages prescriptions for 25 million Americans, said companies and health plans using its national preferred formulary will spend approximately $750 million on alirocumab and evolocumab in 2016. Earlier this week, one executive stated that the company does not anticipate alirocumab or evolocumab being "budget busters."

Dr Steven Miller, chief medical officer at Express Scripts, told the New York Times that the company plans to prevent a massive surge in the use of evolocumab and alirocumab by strictly controlling who can use them. To date, it has rejected half of the prescriptions, in some cases because there was no evidence the patient had elevated cholesterol levels or evidence the patient tried but failed statin therapy.

To heartwire from Medscape, Dr Steven Nissen (Cleveland Clinic, OH) said decision to pay for the new drugs is appropriate, saying it "will make access to these medications easier for patients, which is good for patient care."

Dr Sanjay Kaul (Cedars-Sinai Medical Center, Los Angeles, CA) pointed out that alirocumab and evolocumab are very effective in lowering LDL-cholesterol levels, but given the absence of clinical outcomes data showing a benefit on cardiovascular events, it remains debatable as to whether the wholesale cost is justified. "If the formularies can negotiate a hard discount and restrict utilization strictly to on-label use, that would be a reasonable outcome," Kaul told heartwire .

Express Scripts told the New York Times it had received discounts on the drugs but would not reveal what the company or patients pay for drugs. Miller said the cost of either alirocumab or evolocumab depends on the patient's health plan. "We were able over the course of tough negotiations to get good economics on both products," said Miller.

CVS Health, another large pharmacy benefits manager with 70 million plan members, has not yet made a decision on whether it will add evolocumab or alirocumab to any of its formularies. CVS Health had previously stated it would wait for the approval of both drugs—alirocumab was approved earlier in the summer while evolocumab garnered FDA approval in late August—in order to negotiate price discounts with the drug manufacturers.

Earlier this summer, CVS Health made news when it asked the American College of Cardiology (ACC) and American Heart Association (AHA) to return to goal-based cholesterol targets to limit the uptake of the new drugs. In a perspective, medical officers at CVS Health predicted a worst-case doomsday scenario, where alirocumab and evolocumab added anywhere from $100 billion to $200 billion per year in costs to the US healthcare system. That number would include treating patients with familial hypercholesterolemia (FH) and severe hypercholesterolemia, statin-intolerant patients, and those with a history of coronary artery disease.

Impact on Insurance Premiums

In their perspective, Schulman, along with Duke University researchers Suresh Balu and Dr Shelby Reed, say that the healthcare market is "nearly unique in fostering demand that is seemingly impervious to price escalation." While there is attention being paid to the rising costs of drugs, there is no "magic bullet" that appears able to slow the rising costs of the specialty medication market.

In their calculations, they estimate that every individual within an insurance pool would be forced to pay approximately $124 more in insurance premiums to offset the cost of alirocumab and evolocumab. The increase in premiums would be more if clinical criteria for using the drugs expand. Taxpayers will also bear an additional burden by paying for similar increases in the cost of the Medicare Part D program (where 86% of the program's costs are funded by federal and state taxes).

Schulman and colleagues note that within the pharmaceutical market, industry assumes payment from public and third-party insurance and that the public will eagerly share in those costs. "Clearly, the entry of alirocumab and evolocumab is going to raise questions about whether (primary or secondary) prevention of cardiovascular disease remains an insurable benefit."

Still to Be Determined

Also writing in the New England Journal of Medicine[3], Dr Brendan Everett (Brigham and Women's Hospital, Boston, MA), Dr Robert Smith (Brown University, Providence, RI), and Dr William Hiatt (University of Colorado School of Medicine, Aurora)—all of whom are members of the FDA Endocrinologic and Metabolic Drugs Advisory Committee—provide a perspective on the recent approval of alirocumab and evolocumab.

In the article, the group highlights the known benefits of the new drugs as well as what remains to be determined. As they point out, the agents are extremely good at lowering LDL cholesterol: alirocumab reduces LDL cholesterol 39% to 62% compared with placebo while evolocumab reduces LDL cholesterol 47% to 56% vs placebo.

The advisory panel members acknowledge the absence of hard clinical outcomes with alirocumab and evolocumab, something that two clinical outcomes trials will address in the near future. To date, LDL-cholesterol reduction has been enough to gain FDA approval since lovastatin was approved in 1987 and support for LDL cholesterol as a cardiovascular-event surrogate was recently provided by the IMPROVE-IT study with ezetimibe (Zetia, Merck/Schering-Plough). Everett, Smith, and Hiatt point out other nonstatin drugs, including niacin and fibrates, have lowered LDL but failed to reduce clinical outcomes.

"As substantially as alirocumab and evolocumab reduce LDL cholesterol, definitive evidence of reduced cardiovascular events is essential," they write. "Ongoing trials designed to provide such evidence should elucidate the medications' true clinical benefits and possible risks."

The Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) study is a 27,500-patient trial testing evolocumab against statin therapy for the reduction of the primary composite end point of cardiovascular death, MI, hospitalization for unstable angina, stroke, or coronary revascularization. Full results are expected in 2016, 6 months earlier than previously anticipated. With alirocumab, the ODYSSEY-Outcomes study is similar in design and duration and will include 18,000 ACS patients randomized to PCSK9 inhibition or placebo on top of optimal medical therapy. Full results of the ODYSSEY trial will be available in early 2018.

Shulman reports receiving honoraria from McKesson and Cardinal Health and consulting for Genentech, Novartis, and Sanofi; he held stock until 2013 in Alnylam Pharmaceuticals. Balu and Reed report they have no relevant financial relationships. Everett reports grant support from Novartis Pharmaceuticals, grant and other support from Roche Diagnostics, and personal fees from Genzyme. Hiatt reports grant support from AstraZeneca, Bayer, the National Institutes of Health, and Pluristem. Smith reports he has no relevant financial relationships.


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