Regeneron Pharmaceuticals and Sanofi have presented results from four studies concluding that their cholesterol drug alirocumab (Praluent®) reduced the risk of atherosclerotic cardiovascular disease (ASCVD) in several patient populations.

At the European Society of Cardiology (ESC) Congress 2017, the companies released results from the studies, part of their Odyssey clinical program designed to assess alirocumab in patients at high CV risk.

In one study, patients dosed with 75 or 150 mg of alirocumab every 2 weeks showed significant low-density lipoprotein cholesterol (LDL-C) reductions following 12 weeks of treatment. Patient levels of LDL-C showed an average 55.7% reduction—dropping 54.1% in patients with heterozygous familial hypercholesterolemia (HeFH) and 58.8% in those without HeFH, according to results presented by Bertrand Cariou, M.D., Ph.D., of University Hospital of Nantes, France, and colleagues.

“As hypothesized, the study found a lower risk of ASCVD events with increasingly lower lipid levels, which supports a goal-based treatment strategy for further cholesterol lowering and reduction in ASCVD risk,” a Sanofi spokesperson told GEN.

That is in line with positive results from the ODYSSEY DM-INSULIN study the company presented in June at the 77th Scientific Sessions of the American Diabetes Association (ADA), which showed alirocumab significantly reduced LDL-C in individuals with type 2 diabetes. Additional data from the ODYSSEY DM program will be presented September 14 at the European Association for the Study of Diabetes (EASD) meeting, the spokesperson added.

In another study, Eli Roth, M.D., of Sterling Research Group, and colleagues, showed that alirocumab treatment led to significant reductions in LDL-C that were proportional in size to baseline in patients dosed with 75 mg every 2 weeks, patients starting at 75 mg and switching to 150 mg, and patients dosed with 150 mg.

For patients with the highest baseline LDL-C values (≥190 mg/dL; ≥4.9 mmol/L), absolute LDL-C reductions at week 24 translated to predicted CV risk reductions ranging from 71% in patients switched from 75 to 150 mg, to 74% in patients dosed at 150 mg throughout the trial.

The researchers pooled data from 10 trials according to alirocumab dose: Eight trials used a 75-mg dose every 2 weeks, rising to 150 mg at week 12 if prespecified LDL-C goals were not achieved at week eight. The other two trials were based on alirocumab doses of 150 mg every two weeks.

In the third study, Jamal S. Rana, M.D., Ph.D., of Kaiser Permanente Medical Center, and colleagues, showed that among 62,428 individuals with type 2 diabetes who were treated with statins, a lower risk of CV events was associated with increasingly lower lipid levels.

The fourth study by Antonio J. Vallejo-Vaz, M.D., of Imperial College London, and colleagues, found that high CV risk patients who had higher baseline LDL-C and were younger were more likely to need an increase in their dose of alirocumab to reduce LDL-C.

That study summed up results from the ODYSSEY COMBO I and II trials, in which 637 patients with hypercholesterolemia and high CV risk were randomized to alirocumab 75 mg every 2 weeks or placebo (COMBO I) or alirocumab or ezetimibe (COMBO II) as an add-on treatment to maximally tolerated statin doses, with results measured after 52 and 104 weeks.

A total 114 patients (17.9%) had their alirocumab dosages increased from 75 mg to 150 mg at the 12th week since they showed LDL-C of ≥70 mg/dL (≥1.8 mmol/L) in the eighth week.

The ESC Congress is being held through today in Barcelona, Spain.

No Mortality Measure

While the studies cited lower CV risk, they did not measure results by mortality. An initial interim analysis of results from the first 522 patients studied in the ODYSSEY APPRISE trial (NCT02476006) showed one patient had an event leading to death. “Upon further investigation, it was confirmed that the death did not occur during the exposure period,” the Sanofi spokesperson added.

The interim analysis also showed that 299 patients (57.3%) reported treatment-emergent adverse events, of which 36 (7.3%) had nasopharyngitis and 27 (5.2%) had headaches.

Reduced mortality has been a conclusion of past studies of alirocumab and other cholesterol-fighting drugs in the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor class. Alirocumab won FDA approval in 2015, as did Amgen’s evolocumab (Repatha®).

Evolocumab has been at the center of the debate over the costs and benefits of PCSK9 inhibitors as cholesterol treatments. In the August 22/29 issue of the Journal of the American Medical Association (JAMA), researchers at the University of California, San Francisco (UCSF) concluded that the price of PCSK9 inhibitors would require reduction by 71%, to $4215 a year, in order for the drugs to be cost-effective; the researchers updated their 2016 study, which recommended a target price of just over $4500, closer to the cost of PCSK9 inhibitors in Europe.

But on August 23, an Amgen-funded study published in JAMA Cardiology concluded that the company’s evolocumab was cost effective at net prices at or below $9669 for U.S. clinical practice and $6780 for trial participants, when used in patients at high-risk for CV events. The study distinguished between the net price paid by payers and evolocumab’s list price of $14,523.

Alirocumab is designed to inhibit the binding of PCSK9 to the LDL receptor, thus increasing the number of available LDL receptors on the surface of liver cells, resulting in lower LDL-C levels in the blood.

Alirocumab is approved in more than 50 countries worldwide, including the U.S., Japan, Canada, Switzerland, Mexico, and Brazil, as well as the European Union.

In the U.S., alirocumab is approved for use as an adjunct to diet and maximally tolerated statin therapy for adults with HeFH or clinical ASCVD who require additional lowering of LDL-C.

In the EU, alirocumab is approved for the treatment of adult patients with primary hypercholesterolemia (HeFH and nonfamilial) 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.

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