Amgen Statement Regarding Kazi et al PCSK9 Economic Analysis Published in JAMA

"Cost-effectiveness of PCSK9 Inhibitor Therapy in Patients With Heterozygous Familial Hypercholesterolemia or Atherosclerotic Cardiovascular Disease"

Amgen strongly believes in the clinical and economic value of Repatha. There have been numerous discussions on the value of PCSK9 inhibitors; this analysis is just one view. Another model which has been published and contains transparent peer-reviewed assumptions, demonstrates a value-based price of up to $15,000, which is significantly higher than both the current list price and net price being paid by payers in the U.S.

Given the stakes for patients, we believe any value assessments should aim to achieve the highest level of transparency, strive for very broad stakeholder engagement, and place scientific rigor and patient interests at the center of the analysis.  We remain concerned that these types of assessments are focused on ringing alarm bells from a payer perspective, rather than focusing on a rigorous analysis that fully reflects the patient perspective of value.

Questions and Answers

Q: The recent Kazi et al paper in JAMA states that the PCSK9 inhibitors do not represent value unless the prices are reduced to $4,500 per year, why is this so different from Amgen's price?

There are multiple reasons that the value based price estimates in the Kazi et al paper are different to the current list prices for PCSK9 inhibitors, including the fact that the analysis:

• Models a scenario where PCSK9 inhibitors are dispensed indiscriminately, without clinical judgment to a large, lower risk population not optimized on prior therapy.  This significantly overestimates the number of patients who will receive these medicines. The FDA is clear that PCSK9 inhibitors should only be used in people with clinical atherosclerotic cardiovascular disease, who are receiving maximally tolerated statin treatment and require additional lowering of LDL, as well as patients with heterozygous or homozygous familial hypercholesterolemia,
• Focuses on a population at a three to four times lower risk of CV events, compared to other economic analyses of PCSK9 inhibitors,
• Models a significant overestimation of the population size, resulting in an annual budget impact of $120B which is nearly 400 times higher than 2016 financial analyst consensus estimates,
• Uses a comparator, ezetimibe, as opposed to add on therapy to maximally tolerated statins, which is what has been used in other analyses. Additionally the authors have overestimated the cardiovascular mortality benefit of ezetimibe, which has reduced the estimated incremental value of PCSK9 inhibitors,
• Uses list prices that are higher that the prices actually negotiated with payers; and
• Applies a 100,000 cost per QALY threshold in the main analysis.  Many respectable sources suggest much higher thresholds,which, if used, would significantly change the value-based price estimate.

The value-based price range for PCSK9 inhibitors is far from settled, with estimates from other peer reviewed analyses ranging between $5,000-$17,000 per year, including a recently published analysis that concluded that PCSK9 inhibitors are cost effective at prices in the market today.^1,2,3

Q: The recent Kazi et al paper in JAMA states that the PCSK9 inhibitors will cost the healthcare system $590B over five years, and over $120B per year. Why are those estimates so different from Amgen's estimates?

The Kazi et al paper's estimated budget impact of $120B is nearly 400 times higher than financial analyst consensus estimates.  The author's estimations for the total effect on the U.S. health care budget over the next five years are based on all 9.6 million patients receiving a PCSK9 inhibitor instead of ezetimibe.  However, the current use of ezetimibe in clinical atherosclerotic cardiovascular disease patients is much lower at around ten percent.  

An analysis that assumes add-on therapy will achieve a one hundred percent utilization is not based in reality and not helpful for good decision-making.  

We remain concerned that these types of assessments are focused on ringing 'alarm bells' from a payer perspective and lead to access restrictions that potentially harm patients, rather than focusing on a rigorous analysis that fully reflects the patient perspective of value.

Q: What is the difference between a cost-effectiveness analysis and a broader assessment of the social value of innovation?

The social value of innovation estimates the net monetary benefit of a new therapy over a defined time period across the entire US population. In this case, it estimates the reduction in cardiovascular events due to the introduction of PCSK9 inhibitors and monetizes the associated benefit of life years gained and the reduction in health care costs. In the 2016 study done by Jena et al, they estimated the cumulative value of PCSK9 inhibitors would range from $3.4 trillion- $5.1 trillion (1.9M – 2.8M deaths averted), or $12,000-$17,000 per patient year of treatment.²  In other words, the paper estimated that the value per patient year of treatment was up to $17,000 and concluded that, even in a lower efficacy scenario, value was likely well above discounted prices.

In contrast, a cost-effectiveness analysis is designed to facilitate a comparison of different treatments for specific patient populations and uses outcomes, such as quality adjusted life years (QALY), instead of providing a total value of the entire eligible population.  This analysis tends to be used for informing decisions between alternative treatment options, and therefore, is popular among health technology bodies that rely on a standard outcomes measure across all disease state.  Many centralized healthcare systems use rigid cost-effectiveness analyses to set prices and ration care, and cost-effectiveness thresholds are well-known price controls. 

Q: What does Amgen mean by a 'balanced discussion on value'?

Amgen is focused on helping people with serious diseases by delivering medicines that improve health outcomes, and by collaborating on programs and policies to improve our healthcare system.  Amgen supports having a robust and balanced dialogue about the value of medicines and of PCSK9 inhibitors.  Such a dialogue should be based on realistic assessments of these new medicines, using well-tested and transparent methodology. Value-based discussions should keep the interests of patients at the center of the analysis and take a broad societal perspective related to the costs and benefits of healthcare interventions.  

Q: Why are patients being denied access to PCSK9 inhibitors, is it because the price is too high?

Since its approval, Amgen has negotiated substantial discounts and rebates on the price of Repatha with payers across the U.S. In addition, Amgen has instituted a number of pay-for-performance type contracts with payers to help ensure patients can access the medicine.

Despite agreements on the contracted price of Repatha, insurers have put in place restrictive verification processes using utilization management (UM) criteria that go beyond the FDA-approved label. 

Unfortunately, this is resulting in a large proportion of patients being denied the medication their doctors believe they need. Nearly one year after the FDA approved PCSK9 inhibitors, approximately two thirds of patients continue to struggle to get these medicines from their insurer.

We continue to work with payers to improve the situation and help ensure that appropriate patients are able to access Repatha from their insurers.

Letters to the Editor

Click here to read Amgen’s letters to editors in response to media coverage of the recent JAMA publication.