Every once in a while, a pharmaceutical breakthrough comes along that drastically changes the way a particular disease or a condition is treated and sends ripples through the managed care market as pharmacy benefit managers try to control costs.

The newly approved cholesterol lowering drugs called PCSK-9 inhibitors are one such class that could significantly alter the treatment algorithm in the cardiovascular therapy area. The two drugs, Regeneron/ Sanofi’s alirocumab (Praluent) and Amgen’s evolocumab (Repatha) were approved by the FDA in the second half of 2015 to treat patients with heterozygous familial hypercholesterolemia (HeFH) and atherosclerotic cardiovascular disease (ASCVD), such as heart attacks and strokes, where statin therapy is insufficient to bring down the LDL cholesterol levels effectively.

The annual cost of treatment for Praluent and Repatha are estimated to be $14,600 and $14,100, respectively, about 50 times higher than the yearly cost of therapy for generic statins that are used to treat majority of patients with hypercholesterolemia. Because of that high price tag, PCSK-9 inhibitors are expected to have significant budgetary impact on health plans, pharmacy benefit managers, and any stakeholders negotiating discounts and managing the use of these costly drugs.

PBMs have employed multiple clinical and commercial strategies to manage PCSK-9 inhibitors. Some PBMs have leveraged discounts with drug companies by agreeing to include only one of the drugs on their formularies, and are expecting demonstrable results.

For example, in November 2015, CVS Health reported that its P&T Committee reviewed PCSK-9 inhibitors and determined that Praluent and Repatha were “therapeutically equivalent” and decided to include only Repatha. Moreover, CVS established a value-based arrangement with Amgen, which requires Repatha to lower LDL levels consistent with the results observed in the drug’s clinical trials (about 50% reduction). If the PBM doesn’t see adequate LDL reduction, Amgen will further discount the cost of Repatha. If the drug meets or exceeds expected LDL reduction, the original negotiated price remains applicable.

Meanwhile, some PBMs, such as Express Scripts, are banking on discounts and management strategies such as prior authorization, step therapy and quantity limits to keep costs under control and have included both drugs on formularies. Still others have taken a more conservative approach. Navitus has held off on including the new PCSK-9 inhibitors until the cardiovascular morbidity and mortality outcomes data from ongoing clinical trials of these agents are released in the next couple of years.

Nonadherence to statin therapy is a major concern for PBMs. In October 2015, a Prime Therapeutics study showed that only around 20 percent of patients with ASCVD were adherent to high intensity statin regimens. Convinced that statins are significantly underused by patients with established cardiovascular disease, Prime considered adding the newly approved PCSK9 inhibitors to its national drug list in December 2015. Prime expects that PCSK-9 inhibitors could add $1.34 to $10.31 per member per month, depending on the level of utilization management to its overall drug expenditure.

It is estimated that more than 5 to 10 million adults in the United States live with HeFH or clinical ASCVD currently. While not all eligible patients will be treated with PCSK9 inhibitors in the next couple of years, the national annual spend on this therapy class could touch as high as $100 billion in the near term, if the payers and the PBMs do not implement any cost containment strategies. If those estimates hold true, PCSK9 inhibitors are on the path to become one of the costliest therapy classes.

Most PBMs have already implemented disease management programs, which take into account a patient’s history of heart disease, experience with statin therapy and other related factors before authorizing use of a PCSK9 inhibitors. Express Scripts has introduced a Cholesterol Care Value Program, which focuses on stringent clinical documentation process to provide access only to the eligible patients, while minimizing safety concerns and drug waste.

The future holds answers to some of the critical questions pertaining to PCSK-9 inhibitors that PBMs are keenly looking forward to: What will be the results from ongoing cardiovascular morbidity and mortality outcomes trials? Will the additional clinical trials that are underway for PCSK-9 inhibitors ultimately expand the target patient population, further increasing the potential cost burden? Will PCSK-9 inhibitors become routine alternatives to a low-cost statin therapy, given their favorable efficacy and safely profiles? Will patients adhere to this injectable therapy better than statins that are administered orally?

As payers look more closely at controlling the expenditure on prescription drugs, it will be interesting to see what novel strategies the PBMs will employ to address payer affordability while maintaining patient accessibility. From the PBM’s perspective, the future of the PCSK-9 inhibitors will depend on the breadth of labeling expansions that the drug is able to gain, its long-term real world performance and its acceptance by patients, and ultimately payers.

 

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