資料來源：https://www.prnewswire.com/news-releases/regeneron-and-sanofi-announce-positive-results-from-first-dedicated-studies-evaluating-praluent-alirocumab-in-individuals-with-diabetes-and-hypercholesterolemia-300472008.html

Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Sanofi today announced positive results from two Phase 3b/4 ODYSSEY-DM trials in patients with diabetes. In the studies, Praluent® (alirocumab) when administered on top of maximally tolerated doses (MTD) of statins significantly reduced low-density lipoprotein cholesterol (LDL-C), the primary endpoint of the ODYSSEY-DM INSULIN study, and was superior to usual care in reducing non-high-density lipoprotein cholesterol (non-HDL-C), the primary endpoint of the ODYSSEY-DM DYSLIPIDEMIA study. Both studies also found that a majority of patients reached their lipid goals with Praluent 75 mg every two weeks, with an overall safety profile comparable to the ODYSSEY Phase 3 program.

The results were unveiled today as part of the official symposium of the 77th Scientific Sessions of the American Diabetes Association (ADA) in San Diego, CA, titled, "Inhibition of PCSK9 in Dyslipidemia Patients with Diabetes." The data were also featured in the official ADA Scientific Sessions Advance program.

"Patients with long-standing diabetes, including insulin-treated patients, are at high risk of cardiovascular disease," said Lawrence Leiter, M.D., chair of the ODYSSEY-DM Steering Committee and director of the Lipid Clinic at the Li Ka Shing Knowledge Institute at St. Michael's Hospital, University of Toronto, Canada. "The positive results from ODYSSEY-DM INSULIN provide valuable information on the efficacy and safety of Praluent in this high cardiovascular risk group."

Most people with diabetes will develop atherosclerotic cardiovascular disease (ASCVD). Despite current standard of care, nearly 70 percent of people age 65 or older with diabetes die from some form of heart disease; and 16 percent die of stroke.

"Mixed dyslipidemia is common in people with type 2 diabetes and further increases CV risk, and yet it is difficult to treat with available therapies," said Robert Henry, M.D., member of the ODYSSEY-DM Steering Committee, and Director of the Center for Metabolic Research at the VA San Diego Healthcare System. "The results of ODYSSEY-DM DYSLIPIDEMIA showed that in a real-world setting, Praluent, on top of maximally tolerated doses of statins, significantly reduced non-HDL-C, another measure of bad cholesterol, and was superior to usual care. Based on these results, Praluent may be another option for physicians who need to further help their diabetes patients with clinical ASCVD manage their lipid profiles."

In ODYSSEY-DM INSULIN, patients were randomized to Praluent 75 mg every two weeks or placebo in addition to MTD statins. The Praluent dose was adjusted at week 12 to 150 mg every two weeks if their LDL-C was greater than or equal to 70 mg/dL at week 8. Approximately 80 percent of patients reached their LDL-C goals with Praluent 75 mg every two weeks in this study. In ODYSSEY-DM DYSLIPIDEMIA, patients were randomized to Praluent 75 mg every two weeks or usual care in addition to MTD statins. The Praluent dose was adjusted at week 12 to 150 mg every two weeks if their non-HDL-C was greater than or equal to 100 mg/dL at week 8. Approximately 64 percent of patients reached their lipid goals with the Praluent 75 mg dose.

ODYSSEY-DM INSULIN was a randomized, double blind, placebo-controlled, multicenter study that evaluated Praluent in 517 people with type 1 and type 2 diabetes on insulin with high CV risk and hypercholesterolemia who took MTD statins. The primary endpoint was percent change in calculated LDL-C from baseline to week 24. Results in the type 2 diabetes study population (n=441) were presented at ADA and showed:

Praluent in combination with MTD statins reduced LDL-C by 48.2 percent from baseline compared to a 0.8 percent increase for placebo. The mean difference between the two treatment arms was -49 percent (p<0.0001).

Treatment with Praluent also improved the overall lipid profile.

Overall, Praluent was generally well tolerated. Treatment emergent adverse events (TEAEs) were similar between the two groups and no emerging safety findings were identified from the study. The most frequent TEAEs included nasopharyngitis, myalgia, arthralgia and cough. There was no new safety signal with the concomitant use of Praluent and insulin.

There was no impact on glycemic control as assessed by fasting plasma glucose (FPG), A1C and glucose lowering treatments remained stable over time in both treatment groups.

ODYSSEY-DM DYSLIPIDEMIA was a randomized, open-label, parallel-group study designed to evaluate the superiority of Praluent versus usual care in 413 people with type 2 diabetes and mixed dyslipidemia at high CV risk, not adequately controlled with MTD statins. The primary endpoint was percent change in non-HDL-C from baseline to week 24. Non-HDL-C is calculated as total cholesterol minus high-density lipoprotein cholesterol, and provides a single index of all the potentially atherogenic, apolipoprotein (apo) B-containing lipoproteins, including LDL, very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and lipoprotein(a).

Praluent was superior to usual care in lowering non-HDL-C (37.3 percent and 4.7 percent, for the usual care arm). The mean difference between the two treatment arms was 32.5 percent (p<0.0001).

Praluent in combination with MTD statins reduced LDL-C by 43.3 percent from baseline compared to a 0.3 percent increase for usual care (p<0.0001).

Treatment with Praluent also improved the overall lipid profile.

Praluent was generally well-tolerated. The most frequent TEAEs between treatment groups included urinary tract infection, diarrhea, and nasopharyngitis.

There was no impact on glycemic control observed as assessed by fasting plasma glucose (FPG), A1C and glucose lowering treatments remained stable over time in both treatment groups.

In the previously reported results from the ODYSSEY LONG TERM study in which all patients were treated with Praluent 150 mg on top of MTD statins, Praluent reduced LDL-C by 60 percent from baseline in patients with diabetes (n=545) at week 24.

The recommended starting dose of Praluent is 75 mg administered subcutaneously every 2 weeks, or alternatively 300 mg every 4 weeks (monthly) for patients who prefer less frequent dosing. The majority of patients taking Praluent achieve sufficient LDL-C reduction with the 75 mg dose. If the LDL-C response is inadequate, the dosage may be adjusted to the maximum dosage of 150 mg administered every 2 weeks.

About Praluent

Praluent 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 results in lower LDL-C levels in the blood.

Praluent is approved in more than 50 countries worldwide, including the U.S., Japan, Canada, Switzerland, Mexico and Brazil, as well as the European Union (EU). In the U.S., Praluent is approved for use as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic CV disease, who require additional lowering of LDL-C. In the EU, Praluent is approved for the treatment of adult patients with primary hypercholesterolemia (HeFH and non-familial) or mixed dyslipidemia as an adjunct to diet: a) in combination with a statin, or statin with other lipid-lowering therapies in patients unable to reach their LDL-C goals with the maximally-tolerated statin or b) alone or in combination with other lipid-lowering therapies for patients who are statin intolerant, or for whom a statin is contraindicated. The effect of Praluent on CV morbidity and mortality has not yet been determined. ODYSSEY OUTCOMES is prospectively evaluating the effect of Praluent on the occurrence of CV events in approximately 18,000 patients who have experienced an acute coronary syndrome.

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.