ACC: Investigational PCSK9 inhibitor alirocumab shows promise in phase 3 monotherapy study

Dr RothData from a phase 3 study comparing the low-density lipoprotein-cholesterol (LDLc)–lowering efficacy and safety of alirocumab, an investigational PCSK9 inhibitor, versus ezetemibe in patients not receiving statin or other lipid-lowering therapies, was presented at the American College of Cardiology’s 63^rd Annual Scientific Session & Expo (the ACC.14) in Washington, D.C.

The 24-week ODYSSEY MONO showed that in patients who are not taking statins and receiving a 1-mL, 75-mg dose of alirocumab, which is a new dose lower than previously tested in most clinical trials, are able to achieve a reduction in LDLc reduction of almost 50%, according to the study presenter Eli M. Roth, MD, FACC, medical director, Sterling Research Group.

“The study extends the safety observations from the phase 2 trials; there were no significant adverse events,” Dr Roth told FormularyWatch.

“I think this gives people a potential  option of a new, lower dose that could  be used for patients who are not able to take a statin or other lipid-lowering medication,” he said. “It shows that we get a stable effect that is statistically significant and it gives about 2.5 times the lipid-lowering or ability of ezetimibe, which is the drug commonly used for these types of patients.”

Patients in the study were randomly assigned to either a single 1-mL subcutaneous injection of alirocumab (75 mg) and a placebo tablet, or a placebo injection with an ezetimibe tablet. There were provisions for up-titrating the patients receiving alirocumab patients at Week 12 if their Week 8 LDLc was >70 mg/dL; 14 of the 51 patients were up-titrated in a blinded manner at Week 12 to the 150 mg doing regimen, and 37 patients did not require up-titration.

There are several take-away messages, according to Dr Roth.

“The first is that it could be a potential option for patients who are not on statins, and in the study the lower dose of alirocumab appears to be fairly effective and have a longer term of duration than if the patients were on a statin,” he said. “The second is that you can achieve an approximate 50% reduction in LDL cholesterol, which is what’s now suggested for the highest at-risk patients. And thirdly, this study used an auto-injector, so patients were able to inject themselves every 2 weeks for 24 weeks, and there were very few injection-site reactions.”

This study was funded by Sanofi and Regeneron Pharmaceuticals, Inc.