Inside PCSK9 Inhibitors and Heart Failure Futures New Cardiovascular Treatments: Dollars & Sense

As the healthcare industry shifts towards a more value-based system, payers, physicians, patients and pharmaceutical companies are paying more attention to the costs and benefits of new treatments. Steven D. Pearson, MD, has been interested in those topics for a long time and has emerged as a leading voice when it comes to comparative effectiveness research and health policy.

In 2007, Pearson founded the Institute for Clinical and Economic Review (ICER), a nonprofit healthcare research organization. Pearson, who practiced as a general internist until 2004, is now ICER’s president and a lecturer in the department of population medicine at Harvard Medical School. He also was a special advisor on coverage and technology policy at the Centers for Medicare & Medicaid Services in 2005.

In July, ICER received a $5.2 million grant from the Laura and John Arnold Foundation and launched a program to evaluate new medications from a cost and value perspective. The reports are released publicly and include an analysis of a drug’s comparative effectiveness, cost-effectiveness and potential budget impact.

ICER researchers released a report in September after reviewing the clinical effectiveness and long-term economic value of alirocumab and evolocumab, proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors that the FDA approved this summer. The drugs are touted for their effectiveness in lowering low-density lipoprotein (LDL) cholesterol, although some have raised concerns about the high costs associated with the medications.

“The reason that [PCSK9 inhibitors] ended up on our list of topics was because people viewed them as significant additions to the treatment options for patients with high cholesterol,” Pearson says. “There are a lot of patients with high cholesterol. I think [PCSK9 inhibitors] are going to be very important clinically. I think they will have an important impact on healthcare budgets. Our job is to help sort out whether they provide a good value both for patients and the healthcare system.”

ICER’s researchers include clinicians, clinical epidemiologists, health economists and others. The analysis found that the price that best represents the benefits of the PCSK9 inhibitors should be approximately two-thirds lower than the wholesale acquisition cost (WAC) of the medications.

The annual WAC is $14,600 for alirocumab and $14,100 for evolocumab. Both drugs are injectable medications that lower LDL cholesterol by 55 percent to 60 percent in patients who are receiving statins or cannot take statins.

The costs to Medicare and insurers will vary, but they will be more expensive than the current standard of care of statins alone or statins with ezetimibe, niacin or fibrates, according to Christopher P. Cannon, MD, a steering committee member of the phase 3 program that led to alirocumab’s approval.

Researchers from ICER said the price should be between $3,615 and $4,811 per year based on their overall benefits, although they did not take budgetary concerns into consideration. They estimated between 3.5 million and 15 million Americans may be eligible to receive PCSK9 inhibitors.

When considering budgetary concerns, the researchers suggested an annual drug cost of $2,177 would be more appropriate, which suggests a discount of 85 percent off of the WAC.

They evaluated 25 clinical trials and two systematic reviews and meta-analyses. They noted that approximately one-third of American adults have cardiovascular disease, which is the leading cause of death in the U.S. Although research has indicated statins lower LDL cholesterol and reduce the risk of MI, stroke and death from cardiovascular disease, other drugs that lower LDL cholesterol such as hormone therapy, niacin and torcetrapib do not decrease cardiovascular disease events.

The researchers mentioned that alirocumab and evolocumab had similar reductions in LDL cholesterol and that differences in patients enrolled in clinical trials could explain the small differences in LDL cholesterol.

Although current studies have not determined if the PCSK9 inhibitors lower mortality or cardiovascular disease adverse events, the researchers estimated they could reduce all-cause and cardiovascular mortality by approximately 50 percent. However, they noted the confidence intervals were wide and the number of events was low.

In September, ICER also released reviews of two recently FDA-approved treatments for heart failure. The researchers noted the two interventions could become the first breakthroughs in heart failure management in more than a decade.

For both analyses, the researchers developed a Markov model of the natural history of chronic heart failure using event rates from the published literature. They mentioned that nearly six million people in the U.S. have congestive heart failure, and the lifetime risk of developing the condition is approximately 20 percent.

In July, the FDA approved sacubitril/valsartan (Entresto, Novartis), a twice-daily oral medication to treat patients with heart failure and reduced ejection fraction. Valsartan is an ARB, while sacubitril is a neprilysin inhibitor.

With a WAC of $4,560, sacubitril/valsartan will not save payers and patients money in the long-term, according to the ICER researchers. However, when considering that the medication increases the average life expectancy for patients and decreases the number of congestive heart failure hospitalizations, it is cost-effective based on accepted thresholds.

The researchers estimated that nearly two million patients could receive sacubitril/valsartan in the next five years, which could be costly. To meet ICER’s value-based price benchmark, the cost of the drug should be $3,779 per year, which is a discount that payers typically can achieve in negotiations with pharmaceutical companies. They compared sacubitril/valsartan with the current standard of care of an ARB or ACE inhibitor with co-administration of beta blockers.

The CardioMEMS device received FDA approved in May 2014, three years after the FDA rejected its application. The device includes a small wireless sensor and portable electronic transmitter, in which patients wirelessly transmit pulmonary artery pressure readings to an online database. Pulmonary artery pressure is an important indicator of worsening congestive heart failure.

The ICER researchers said the list price for the device is $17,750, which does not include the costs associated with surgical implantation or monitoring. Although they said there was insufficient evidence to determine if the CardioMEMS device improved patient outcomes, they noted that the value-based price benchmark should be $7,622, which is nearly 60 percent off the list price.

They mentioned that the costs associated with the device were incurred at the time of implantation and that ongoing monitoring and other costs were around $27 per month. They compared the device with usual congestive heart failure monitoring.

After releasing its reports, ICER seeks input from the public, clinical experts, drug manufacturers and patient groups, votes on the strength of the evidence for various patient populations and recommends how the evidence could be applied in practice or coverage policy. ICER has a formal topic selection criteria and convenes advisory boards when determining which medications and treatments to review.

“It basically is a mix of things around which it appears that there will be serious questions, sometimes controversies, related to the evidence for which patients [the treatments] work best and in whom they should be used in first-line or second-line,” Pearson says. “Almost always, it’s also something that’s going to have a large impact on patient health and budgets. We have other things we look at, too, in terms of whether there are variations in coverage policies because when there are variations that usually suggests that more evidence and discussion could help.”