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ODYSSEY OUTCOMES: Value of alirocumab increases with higher baseline LDL
CHICAGO — The PCSK9 inhibitor alirocumab was cost effective up to $6,319 per year at a willingness to pay threshold of $100,000, according to an economic analysis of the ODYSSEY OUTCOMES trial presented at the American Heart Association Scientific Sessions.
As Cardiology Today previously reported, reducing LDL to very low levels with alirocumab (Praluent, Sanofi and Regeneron) lowered risk for major adverse CV events and all-cause mortality in patients with ACS on statin therapy. The full results from the ODYSSEY OUTCOMES trial were published on Nov. 7 in The New England Journal of Medicine.
In the ODYSSEY OUTCOMES trial, 18,924 patients with ACS who were on a high-intensity or maximally tolerated dose of atorvastatin or rosuvastatin were assigned alirocumab or placebo every 2 weeks, Deepak L. Bhatt, MD, MPH, professor of medicine at Harvard Medical School, executive director of interventional cardiovascular programs in the Heart and Vascular Center at Brigham and Women’s Hospital and Cardiology Today’s Intervention Chief Medical Editor, said during the presentation.
The primary endpoint was the time to first occurrence of nonfatal MI, CHD death, ischemic stroke or unstable angina that required hospitalization. Secondary endpoints included CV and all-cause death. Follow-up was conducted for a median of 2.8 years.
In the current study, researchers analyzed the diagnosis-related group cost based on Medicare, which was applied to CV death and recurrent nonfatal events including ischemic stroke, MI, unstable angina requiring revascularization and coronary revascularization.
The costs from reimbursement rates that were used in this analysis were the following:
- $20,225 for CV death,
- $18,862 for nonfatal MI without revascularization,
- $12,617 for nonfatal ischemic stroke, and
- $39, 531 for ischemia-driven coronary revascularization or unstable angina.
Other information that was considered included long-term survival probability, health-related quality of life and treatment effect.
The HR in the intention-to-treat population for alirocumab vs. placebo was 0.85, 0.71 for patients with LDL ≥ 100 mg/dL and 0.95 for those with an LDL less than 100 mg/dL.
Compared with the annual event rate per 100 patient-years for patients assigned placebo, those assigned alirocumab had a lower annual event rate per 100 patient-years for CV death (0.89 vs. 1.01), nonfatal MI (3.2 vs. 3.69), nonfatal ischemic stroke (0.44 vs. 0.62), unstable angina (0.14 vs. 0.24) and ischemia-driven coronary revascularization (3.19 vs. 3.7).
The annual price of alirocumab to be cost effective was $100,000 per quality-adjusted life year for the population with a $6,319 base case in the intention-to-treat population. In addition, the annual price for the drug to be cost-effective for a patient with baseline LDL ≥ 100 mg/dL was $13,357 and was $2,083 for those with a baseline LDL less than 100 mg/dL.
The cost effectiveness of alirocumab was less in patients with a baseline LDL less than 100 mg/dL compared with those with an LDL greater than 100 mg/dL in the overall intention-to-treat population regardless of the willingness to pay, according to the researchers.
“Based on both absolute clinical benefit and cost-effectiveness, alirocumab may offer good value in patients with a history of ACS and LDL cholesterol greater than or equal to 100 mg/dL despite maximally tolerated statin therapy,” Bhatt said during the presentation.
“We need to see how patient perspectives and preferences and patient-level costs factor into this cost effectiveness,” Andrew E. Moran, MD, assistant professor of medicine at Colombia University Medical Center, said during the discussant portion of the presentation. “It could be that the patients taking a medication every other week increases their convenience and they might prefer it to taking a daily pill. On the other hand, taking injections might be something that patients are averse to.”
Results from this study may affect both patients and clinicians, experts said.
“[The ODYSSEY OUTCOMES Economics Study] is going to have a great effect,” Robert Sanchez, PhD, senior director of health economics and outcomes research for Regeneron, told Cardiology Today. “The cost-effective price at the $100,000 willingness to pay threshold is $6,000 per year. However, if you limit it to those who had a baseline LDL-C of greater than 100 [mg/dL], the cost-effective price jumps up to about $13,500 per year,” “That falls well within the current rebate structures that we offer in the United States.”
“When I look at the patients with the LDLs above 100 [mg/dL], these are some of the patients that concern me the most as a cardiologist,” Jay Edelberg, MD, head of CV development for Sanofi, said in an interview. “I’ve had a lot of patients who’ve had events in whom I can’t get their LDL under control, and they have not just another event, but recurrent events. Now we have a treatment that can really get these patients under control.” – by Darlene Dobkowski
Reference:
Bhatt DL, et al. LBS.01 – Late Breaking Clinical Trial: Answers to Critical Questions in Cardiovascular Prevention. Presented at: American Heart Association Scientific Sessions; Nov. 10-12, 2018; Chicago.
Disclosures: The ODYSSEY OUTCOMES study was funded by Sanofi Aventis and Regeneron. Bhatt reports he has financial ties with numerous drug and device companies, including receiving research funding from Regeneron and Sanofi. Moran reports no relevant financial disclosures. Edelberg is an employee of Sanofi. Sanchez is an employee of Regeneron.
Perspective
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You can do economic studies of new drugs in two ways. One is to build a simulation model, and the other way is to collect economic outcome data as part of a randomized trial. This study is a hybrid of these two approaches — initial data from the trial with projections of long-term consequences. It’s the first time that economic data from a PCSK9 inhibitor trial was reported, which is a step in the right direction.
There are a lot of steps in between patient access to the drugs and this economics study. Recent price reductions, specifically list price reductions, should reduce out-of-pocket payments by patients. We know that high out-of-pocket payments reduce use of any drug. If prices of PCSK9 inhibitors come down as a result of economic analyses like this one, which concludes the price should be lower to provide value, then that will help, but it’s important to say that prices for PCSK9 inhibitors are still very high.
These preliminary results are welcome. The authors should finish up the analyses and publish the results of the study in a peer-review journal. I’m very interested in what they report, which is provocative yet incomplete until it undergoes peer review. They haven’t, for instance, costed all the subsequent outcomes, which may be important. It needs to undergo some peer review. I’d like to see that happen.
There is also the preponderance of the evidence — evidence from this study too — that the prices of PCSK9 inhibitors certainly need to come down from at least the original level that they were of $14,000. They’re moving down from that, but what the right level is, we still need to figure that out. Lower is better in terms of price, not just LDL levels.
The value price the authors recommend, about $6,000, is based on a fair threshold for an acceptable high cost effectiveness ratio. The value would be even better if the price were lower than $6,000. That’s not a good value price necessarily, but it is closer to what the market might bear.
It’s very important that the researchers also examined the cost effectiveness of different thresholds of LDL before starting PCSK9 inhibitors. They showed quite convincingly that you get more bang for the buck if you treat patients who have LDLs above 100 mg/dL on statins, and it’s not a good value for patients with LDL levels between 70 mg/dL and 100 mg/dL. That’s an important finding that should be investigated further. It’s believable that the higher the LDL level is, the higher the benefit of treatment — those with LDLs over 100 mg/dL are higher-risk patients who probably have more to gain from taking this medication.