Best candidates for PCSK9 inhibitors

Starting in December 2013, pharmacy benefits managers (PBMs) and insurers scrambled to decide which of the new hepatitis C drugs to put on their formularies. The efforts provided a test run for many in determining which of the two new PCSK9 drugs to place on their drug lists.

FDA approved Sanofi-Regeneron’s Praluent (alirocumab) in July 2015, followed by Amgen’s Repatha (evolocumab) one month later. Both drugs, representing a new class of medications to help lower LDL cholesterol, are self-injectables taken every two weeks. They target the proprotein convertase subtilisin/kexin type 9 enzyme, which blocks the liver from lowering LDL cholesterol.

PCSK9 drugs cost much more than statins used to treat the majority of patients with high cholesterol-as much as 50 times more annually, Adam Kautzner, PharmD, vice president, drug trend & formulary at Express Scripts, recently told Managed Healthcare Executive.

Prime Therapeutics predicts that costs of the new class of drugs could be as much as $23.3 billion annually. Praluent costs $14,600, while Repatha sells for $14,100.

An estimated 8 million to 10 million Americans are expected to have arteriosclerotic cardiovascular disease or heterozygous familial hypercholesterolemia (HeFH) in need of further reduction in LDL cholesterol, according to the National Health and Nutrition Examination Survey 2011 to 2012.

Formulary decisions

Winston Wong, president of W-Squared Group, emphasizes that utilization should be limited to patients who could really benefit from the drugs-populations including patients with a confirmed diagnosis of HeFH; statin-resistant patients who do not achieve expected LDL cholesterol reduction with maximal doses of two potent statins; and patients with a confirmed statin intolerance.

OptumRx, which selected only Praluent for its formulary based upon clinical review and a better pricing contract, has taken proactive approaches to ensure that the use of the new, high-cost specialty product is limited to only those patients for which it would be the most clinically appropriate for use.  

“We employ evidence-driven, prior authorization protocols to ensure that only the most appropriate individuals are put on these therapies,” says David Calabrese, vice president and chief pharmacy officer for the PBM. “This includes, but is not limited to, a review of that individual’s diagnosis and previous medical history; previous lipid-lowering drug therapy; duration, dosing and adherence to the therapy; cholesterol-lowering effects and tolerability of therapy to date; and screening for any potential conflicts or contraindications.”

Next: Prior authorization criteria

OptumRx crafted a set of prior authorization criteria based upon available scientific evidence and FDA-labeling to ensure only the most appropriate use of these products and to achieve optimal balance between quality, access, therapeutic value and economic efficiency. 

Like OptumRx, Express Scripts is cautious about putting members on PCSK9 drugs. The PBM is targeting those who have had prior heart attacks or strokes while taking statins.

But unlike OptumRx, Express Scripts elected to put both Praluent and Repatha on its national preferred formulary. Steve Miller, MD, chief medical officer for Express Scripts, says Amgen and Sanofi-Regeneron agreed to provide substantial discounts on their drugs, combined with Express Scripts rigorous utilization program and a cap on the entire plan cost for PCSK9 drugs in 2016. The cap only affects payers and patients enrolled in its Cholesterol Care Value Program (CCV). The program deploys clinical documentation to ensure the right patients gain access to the inhibitors, minimizing unnecessary risks and wasteful spending.

“Through the CCV Program, we anticipate that we will be able to prevent up to 90% of potential cost increases among cholesterol medications for participating plan sponsors,” Miller says.

Patients in the program receive the medications through Express Scripts’ Accredo Specialty Pharmacy, along with access to specialists, videos on self-injection methods and adherence reminders.

Miller anticipates spend on these drugs for 2016 to be $750 million, lower than industry estimates.

Express Scripts has the ability to update the formulary status of the two inhibitors based on new clinical data, competitive drugs in the marketplace and preferences of physicians and patients.

Next: Utilization rates

Utilization rates

Calabrese says it is too early to draw any clear conclusions on utilization because patient numbers are currently limited and in turn, data are not of sufficient volume or duration.

In addition, he points out that true outcomes data, such as impact on longer term cardiovascular morbidity and mortality, will not be evident until such studies are completed by manufacturers some time in 2017 or 2018.

Miller agrees that the long-term effects of PCSK9s are not yet known, but anticipates that as more clinical information is available about the drugs and they prove to be better than statins, the population that could benefit should increase in 2017.

Calabrese also says the uptake by doctors prescribing the drugs is low based on a lack of outcomes data, their injectable administration and the availability of much less costly, well-tested generic alternatives, such as high-potency statins with very solid long-term, outcomes data.

Wong agrees with Calabrese that current utilization is very low-probably lower than expected. Cardiologists, he assumes, are being very specific about patients for whom they prescribe PCSK9s, and most of those patients are meeting criteria.  

Although he recognizes that the new drugs are as effective as claimed in producing a higher level of cholesterol reduction, the issue is whether every case of high cholesterol will require such a decrease. “Current therapies will provide an adequate reduction if taken properly," he says.  

Next: Discounts lead to formulary inclusion

Discounts lead to formulary inclusion

Prime Therapeutics also put both drugs on its national drug list for 25 million commercial and managed Medicaid lives, deeming the two drugs clinically equivalent. The PBM stipulates prior authorization for its commercial population and for its 1 million Medicare beneficiaries. Prime requires Part D Medicare members to take a trial of Praluent prior to a full prescription to ensure the medication is effective.

The PBM relies on its Cholesterol Best in Care drug management program to oversee utilization of both drugs.

Prime has negotiated outcomes-based contracts with both PCSK9 manufacturers, including adherence and utilization cap components, the latter to protect Prime’s clients from unanticipated increases in utilization.

Harvard Pilgrim Health Care chose to cover only Repatha and has negotiated a pay-for-performance contract with Amgen, putting the manufacturer at financial risk. If Repatha does not lower LDL as promised by clinical trials, Amgen would have to provide an enhanced discount to Harvard Pilgrim members. 

Like Express Scripts and Prime, Harvard Pilgrim introduced a cap feature. Additional discounts are available if utilization of the drug exceeds certain levels.

CVS Health also elected to cover just Repatha although it requires prior authorization. The PBM has indicated that it received a substantial discount from Amgen in return for the exclusive relationship.

Next: New cholesterol guidelines

New cholesterol guidelines

While the 2002 federal cholesterol guidelines recommended that people should only take a statin if their 10-year risk level exceeded 20%, a 2013 cholesterol guideline developed by the American Heart Association and American College of Cardiology says an estimated 33 million Americans without cardiovascular disease who have a 7.5% or higher risk for a heart attack or stroke within the next 10 years could take a statin.

The 2013 treatment advice uses a more qualitative assessment of heart and stroke risks in place of numerical targets for LDL cholesterol. Its primary goal for treatment is cardiovascular event reduction achieved by identifying four groups of primary and secondary prevention patients based on age, diabetes, high levels of LDL cholesterol and those presenting with atherosclerotic cardiovascular disease. The guideline recommends appropriate intensities of statin therapy to achieve relative reductions in LDL cholesterol.

Mari Edlin is a frequent contributor to Managed Healthcare Executive. She is based in Sonoma, California.

Sidebar: In the pipeline

Pfizer is preparing to enter the PCSK9 market with a drug called bococizumab. The drug manufacturer is currently in phase 3 trials. Pfizer’s therapies include an injection, a pill and a vaccine that would prevent high cholesterol using immunotherapy. 

Eli Lilly has a monoclonal antibody candidate in phase 2 testing. There are another five treatments in phase 1 trials.