Jennifer G. Robinson
MIAMI — As a result of price reductions for PCSK9 inhibitors from late 2018 and early 2019, the treatment may be expected to be cost-effective in patients with extremely high, very high and high risk for atherosclerotic CVD, according to a National Lipid Association statement presented at the association’s Scientific Sessions.
The statement has also been published in the Journal of Clinical Lipidology.
“The purpose of this statement was to help us update our decision making, ever since the 2018 guideline came out, in terms of new discounting and also the potential for benefit in a wider range of patients,” Jennifer G. Robinson, MD, professor and director of the Preventive Intervention Center at The University of Iowa College of Public Health in Iowa City, said during the presentation.
The 2018 American Heart Association/American College of Cardiology cholesterol guideline stated consideration of PCSK9 inhibitors is reasonable, although the treatment was not given a Class I recommendation due to cost, according to the presentation.
Since 2015, there has been a 60% price reduction for PCSK9 inhibitors from $14,000 per year to $5,850 per year for both evolocumab (Repatha, Amgen) and alirocumab (Praluent, Regeneron/Sanofi).
“I think this is the first time that the list price has been reduced,” Robinson said during the presentation. “PCSK9 monoclonal antibodies are still expensive drugs for this prevention space, and payers have been hesitant to allow us to use them.”
Researchers performed a systematic review of all of the clinical trials that have used moderate- to high-intensity statins or PCSK9 inhibitors in addition to statin therapy. Through this, researchers were able to determine the burden and activity of clinical ASCVD and the presence of adverse or poorly controlled cardiometabolic risk factors in patients with extremely high 10-year ASCVD risk, very high 10-year ASCVD risk and high 10-year ASCVD risk. These categories expand the very high risk category identified in the 2018 guidelines, according to the presentation.
In a paper published in the Journal of the American College of Cardiology in 2016, researchers determined that a about a 60% reduction of $5,400 a year would result in a reasonable value at $100,000 per quality-adjusted life-year when if between 21 and 28 patients were treated to prevent one ASCVD event over a 5-year period. Even greater discounts such as 77% and 85% would lead to even lower costs per quality-adjusted life-years.
In patients with extremely high 10-year ASCVD risk, or a greater than 40% 10-year ASCVD risk, would provide a reasonable value when initial LDL levels were over 70 to 100 mg/dL. PCSK9 inhibitor treatment in these patients was of high value in patients with initial LDL levels above 100 mg/dL.
“This is a no-brainer for payers,” Robinson said during the presentation. “This is a group … where adding a PCSK9 inhibitor could provide a high-value benefit.”
In patients with very high 10-year ASCVD risk, who have a 30% to 39% 10-year ASCVD risk, there was a reasonable value with the use of PCSK9 inhibitors in those with LDL over 100 mg/dL. The value was not as good in patients with index LDL between 70 mg/dL and 100 mg/dL.
Patients with high 10-year ASCVD risk, who have a 20% to 29% 10-year ASCVD risk, had reasonable value with PCSK9 inhibitors, when LDL levels were over 130 mg/dL.
“This is even an expanded group from the guideline where it would be reasonable to treat them with higher LDL levels,” Robinson said during the presentation.
Authors of the statement also focused on familial hypercholesterolemia, which was also mentioned as part of the 2018 AHA/ACC guideline as a patient population who may benefit from PCSK9 inhibitors.
“This group of patients should experience reasonable or even high value when LDL-C levels from PCSK9 monoclonal antibodies when are over 100 mg/dL at the new pricing,” Robinson said during the presentation.
Patients with heterozygous FH have a 20-fold higher lifetime ASCVD risk compared with 5-fold in those with severe hypercholesterolemia with LDL greater than 190 mg/dL and without heterozygous FH, according to the presentation.
“Many of those patients may not be as high risk or fit into these categories,” Robinson said.
In these patients, there was a high value for PCSK9 inhibitors for secondary prevention in patients with genetic hypercholesterolemia or severe hypercholesterolemia who had an LDL over 100 mg/dL.
“That’s better than almost anything else we give in a clinic that’s not generic in terms of high value,” Robinson said.
There was also a reasonable value for these patients with LDL greater than 70 mg/dL. Results were similar for high and reasonable value for primary prevention in these patients.
Compared with patients with LDL levels between 70 mg/dL and 100 mg/dL, those with LDL levels greater than 100 mg/dL who were treated with PCSK9 inhibitors have an additional 10% risk reduction for total mortality and an additional 14% risk reduction for CV mortality per 40 mg/dL higher baseline LDL.
“When LDL-C levels are over 100 mg/dl, that’s where we get the full, relative risk reductions that include mortality benefits in these patients,” Robinson said. – by Darlene Dobkowski
Robertson JG, et al. NLA Statement on Enhancing the Value of PCSK9 Inhibitors. Presented at: National Lipid Association Scientific Sessions; May 16-19, 2019; Miami.
Robertson JG, et al. J Clin Lipidol. 2019;doi:10.1016/j.jacl.2019.05.005.
Disclosures: Robertson reports her institution has received research grants from Acasti, Amarin, Amgen, AstraZeneca, Esai, Esperion, Merck, Pfizer, Regeneron, Sanofi, and Takeda and has consulted for Amgen, Merck, Novartis, Novo Nordisk, Pfizer, Regeneron and Sanofi. Please see the study for all other authors’ relevant financial disclosures.