Dhruv S. Kazi
An analysis of the FOURIER trial did not change previous findings that using PCSK9 inhibitors to treat patients with atherosclerotic CVD was not cost-effective, according to a research letter published in JAMA.
In a separate analysis published in JAMA Cardiology, researchers concluded that for evolocumab (Repatha, Amgen) to be considered cost-effective, the annual net price would need to be reduced to under $10,000, or a higher-risk population would need to be treated with it.
Cost-effectiveness in adults
Dhruv S. Kazi, MD, MSC, MS, attending physician at Zuckerberg San Francisco General Hospital and Trauma Center, and colleagues updated their original analysis of PSCK9 inhibitor cost-effectiveness from 2016 to include updated prices and results from the FOURIER trial.
Researchers used the Cardiovascular Disease Policy Model to estimate cost-effectiveness of PCSK9 inhibitors — evolocumab and alirocumab (Praluent, Sanofi-Regeneron) — or ezetimibe with statin therapy in 8.9 million U.S. adults (mean age, 66 years; 61% men; mean LDL, 104 mg/dL) with atherosclerotic CVD who met the criteria from the trial.
The incremental cost-effectiveness ratio was the primary outcome. The secondary outcome was the cost at which PCSK9 inhibitors would be cost-effective at a willingness-to-pay threshold of $100,000 per quality-adjusted life-year.
Current wholesale acquisition costs were used for PCSK9 inhibitors ($14,542; 1% increase from 2015 to 2017) and ezetimibe ($3,818; 32% increase from 2015 to 2017). Researchers also analyzed data to reflect the results from FOURIER, which showed evolocumab (Repatha, Amgen) lowered risk for MI and stroke but not CV death.
The policy model reproduced major adverse events rates from FOURIER in patients treated with only a statin and patients treated with a statin in addition to PCSK9 inhibitors.
PCSK9 inhibitors reduced an estimated 2,893,500 more adverse events compared with ezetimibe with incremental health care costs of $450,000 per QALY (80% uncertainty interval, 301,000-787,000).
Effects on QALYs
The annual cost of PCSK9 inhibitors would need to be reduced by 71% to achieve a threshold of $100,000 per QALY, Kazi and colleagues wrote, noting that without an effect on CV death, the incremental health care costs increased to $1,795,000 per QALY.
“Although computer simulations that synthesize data from observational studies and clinical trials may not precisely reflect clinical effectiveness that may be observed in practice over time, these updated results continue to demonstrate that reducing the price of PCSK9 inhibitors remains the best approach to delivering the potential health benefits of PCSK9 inhibitors therapy at an acceptable cost,” Kazi and colleagues wrote.
A company spokesperson from Amgen issued a statement by email to Cardiology Today expressing concern that the analysis could help prevent patients from getting access to a needed therapy.
“Several published analyses have shown value-based price ranges that support our current average net selling price, which has been incorporated in several value-based arrangements with payers. Key differences that need to be considered are real-world event rates and value for patient life-years in the U.S.,” the spokesperson wrote. “We continue to be very concerned about these analyses and the impact they may have on patient care by not adequately reflecting the value and becoming a tool for blocking patient access. The Repatha outcomes study taught us that patients with prior [CV] events remain at high risk of additional [CV] events, including [MIs], strokes and the need for revascularization despite optimal statin therapy, so there is an urgency to identify and treat these patients.”
Daniel B. Mark
“Painful as it is, draconian restrictions on access to drugs that are priced for profit maximization out of proportion to any value proposition and budget tolerances may continue to be the only way medicine can send a strong signal to innovators that their future rewards are tied not just to scientific advancement, but also to affordability,” Daniel B. Mark, MD, MPH, professor of medicine at Duke University Medical Center and director of outcomes research at Duke Clinical Research Institute, and Kevin A. Schulman, MD, MBA, professor of medicine at Duke University and associate director of the Duke Clinical Research Institute, wrote in a related editorial. “This is not just an issue for pharmaceutical companies. Profit maximization behavior in medicine out of proportion to value provided is widespread. Ultimately, this message will need to be heeded by the entire health care enterprise.”
Exceeding cost-effectiveness thresholds
In a separate study in JAMA Cardiology, Gregg C. Fonarow, MD, director of the Ahmanson-UCLA Cardiomyopathy Center, co-director of the UCLA Preventative Cardiology Program, co-chief of the UCLA Division of Cardiology and the Eliot Corday Chair in Cardiovascular Medicine and Science, and colleagues found that the current price of evolocumab ($14,523) in addition to standard background therapy to treat patients with atherosclerotic CVD surpassed “generally accepted cost-effectiveness thresholds.”
Gregg C. Fonarow
The addition of evolocumab was linked to an increase in incremental cost ($105,398). Incremental QALYs improved by 0.39, with an incremental cost-effectiveness ratio of $268,637 per QALY gained. Evolocumab would need to cost an annual net price of $9,669, or with a discounted net price of $10,311 for patients with LDL ≥ 80 mg/dL, to achieve an incremental cost-effectiveness ratio of $150,000 per quality-adjusted life-year gained, Fonarow and colleagues wrote.
“These findings highlight the need for a comprehensive disease management approach for [atherosclerotic] CVD that includes vigorous lifestyle changes, assiduous adherence to all guideline-directed therapies and judicious use of new, more costly therapies,” the researchers wrote.
“This study affirms the clinical benefits and economic value of delivering Repatha to the right high-risk patients, specifically patients who have had [an MI] or stroke with high LDL levels despite maximally tolerated statin therapy,” Joshua Ofman, MD, senior vice president of global value, access and policy at Amgen, said in a company press release. “The actual net prices for payers in the market today after discounts and rebates are quite aligned to the value-based price range identified in this study. While the list price is more often quoted in the media, it is the discounted net price that is actually paid by payers and that should be considered in value assessments.”
In a related editorial, Mark and colleagues wrote, “We must … not lose sight of the fact that money spent on PCSK9 [inhibitor] therapy could be invested by health systems to make better use of the affordable drugs we already have (eg, improving adherence to statins and prescribing the most effective doses of statins). There are several other innovative products in the pipeline that also target PCSK9. The opportunities are tremendous for a company that could produce a new drug that can match the effects of PSCK9 [inhibitor] therapy at a more affordable price.” – by Darlene Dobkowski
Fonarow GC, et al. JAMA Cardiol. 2017;doi:10.1001/jamacardio.2017.2762.
Kazi DS, et al. JAMA. 2017;doi:10.1001/jama.2017.9924
Mark DB, et al. JAMA. 2017;doi: 10.1001/jama.2017.8907
Mark DB, et al. JAMA Cardiol. 2017;doi:10.1001/jamacardio.2017.2911.
Disclosures: The study by Fonarow and colleagues was funded by Amgen. Kazi reports no relevant financial disclosures. Mark reports receiving grants from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Gilead, Merck and Oxygen Therapeutics, and consulting fees from Janssen and Medtronic. Schulman reports receiving research support from Amylin Pharmaceuticals and Merck, serving as a board member of Bivarus, board of directors for Cue Biologics the scientific advisory board for Cardinal Analytx and the board for Anthelio. Fonarow reports consulting for Amgen, Janssen and Novartis. Ofman is an employee of Amgen. Please see the studies and editorials for all other authors’ relevant financial disclosures.
Editor’s Note: This article was updated on August 22, 2017, to add a statement from Amgen. It was further updated on August 24, 2017, to add findings from the JAMA Cardiology study and a statement from Amgen on it, and to add a perspective from Dr. Baum. On August 25, 2017, it was updated to add a perspective from Dr. Malone.