Alirocumab injection (Praluent, Regeneron Pharmaceuticals/Sanofi) reduced the risk of major cardiac events by 15% among patients who had suffered heart attacks and other coronary events in the ODYSSEY OUTCOMES trial. The two companies have announced that they are willing to offer price breaks on the costly medication.
ODYSSEY OUTCOMES results were presented at the American College of Cardiology's 67th Annual Scientific Session in Orlando, Florida. Alirocumab met the primary endpoint by reducing the overall risk of major adverse cardiovascular events (MACE) in patients who had suffered a recent acute coronary syndrome (ACS) event (hazard ratio [HR], 0.85; confidence interval [CI], 0.78–0.93; P = 0.0003). The MACE composite endpoint includes patients who experienced a heart attack, ischemic stroke, death from coronary heart disease (CHD), or unstable angina requiring hospitalization.
Alirocumab was also associated with lower all-cause mortality (HR, 0.85; CI, 0.73–0.98; nominal P = 0.026), and there were numerically fewer CHD deaths (HR, 0.92; CI, 0.76–1.11; P = 0.38). Patients with baseline low-density lipoprotein-cholesterol (LDL-C) at or above 100 mg/dL experienced a more pronounced effect from alirocumab , reducing their risk of MACE by 24% (HR, 0.76; CI, 0.65–0.87). In a post-hoc analysis of this group, alirocumab was associated with a lower risk of death from any cause by 29% (HR, 0.71; CI, 0.56–0.90).
These analyses include the results from 730 patients (8%) in the alirocumab group who continued to be assessed in the alirocumab arm despite stopping active alirocumab therapy, as specified in the protocol for patients with persistent LDL-C readings below 15 mg/dL. For those in the alirocumab treatment arm, approximately 75% of patient time was on the 75 mg dose.
There were no new safety signals in the trial.
Regeneron and Sanofi announced that they will “offer payers that agree to reduce burdensome access barriers for high-risk patients a further reduced net price … in alignment with a new value assessment for high-risk patients from the Institute for Clinical and Economic Review (ICER).” Based on the results of ODYSSEY Outcomes, ICER said it had calculated two new value-based price benchmarks for alirocumab in patients with a recent ACS event: $2,300–$3,400 per year if used to treat all patients who meet trial eligibility criteria, and $4,500–$8,000 per year if used to treat higher-risk patients with LDL-C of at least 100 mg/dL despite intensive statin therapy.
"Inventing innovative medicines only matters if the people who need these products are able to access them—and that is unfortunately not the case with Praluent today," said Leonard S. Schleifer, MD, PhD, President and Chief Executive Officer of Regeneron. Regeneron and Sanofi will meet with health plans to discuss potential net pricing adjustments for those that agree to provide straightforward access for high-risk patients.
ODYSSEY OUTCOMES (N = 18,924) assessed the effect of alirocumab on the occurrence of MACE in patients who had experienced an ACS between 1–12 months (median, 2.6 months) before enrolling in the trial, and who were already on maximally-tolerated statins. All patients were randomized to receive alirocumab (n = 9,462) or a placebo (n = 9,462) and were treated for a median of 2.8 years, with some patients being treated for up to five years. Approximately 90% of patients were on a high-intensity statin.
The trial was designed to maintain patients' LDL-C levels between 25–50 mg/dL, using two different doses of alirocumab (75 mg and 150 mg). Alirocumab -treated patients started the trial on 75 mg every two weeks, and switched to 150 mg every two weeks if their LDL-C levels remained above 50 mg/dL (n = 2,615). Some patients who switched to 150 mg switched back to 75 mg if their LDL-C fell below 25 mg/dL (n = 805), and patients who experienced two consecutive LDL-C measurements below 15 mg/dL while on the 75 mg dose (n = 730) stopped active alirocumab therapy for the remainder of the trial.
Alirocumab inhibits the binding of PCSK9 (proprotein convertase subtilisin/kexin type 9) to the LDL receptor and thereby increases the number of available LDL receptors on the surface of liver cells, which lowers LDL-C levels in the blood. In the U.S., alirocumab is approved for use as an adjunct to diet and maximally-tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease who require additional lowering of LDL-C.