Updates showing positive results in ongoing trials of a new type of cholesterol-lowering drug generated a lot of interest at the American College of Cardiology’s (ACC) recent annual meeting in Washington, D.C.
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Still in their trial phase, the PCSK9 inhibitor-type drugs show encouraging promise as a new treatment option for statin-intolerant patients.
Answer to statin intolerance
Millions of people take statin medication, successfully lowering levels of “bad” LDL cholesterol. Statins can cause side effects in some people, though, particularly muscle pain that makes the drug intolerable. PCSK9 inhibitors are a different class of cholesterol-reducing drug that raises hopes for patients who cannot tolerate statins.
PCSK9 inhibitors have been found to reduce LDL levels 50 percent or more. So far, they do not appear to cause the type of troubling side effects associated with statin use, according to preliminary trial results.
PCSK9 studies echo positive results
Reports from several ongoing trials studying the efficacy and safety of PCSK9 inhibitors as cholesterol-lowering drugs stirred great interest at the ACC meeting.
Among the competing new-generation drugs are Pfizer’s bococizumab and Regeneron’s alirocumab. Amgen’s evolocumab received heightened interest, with five trials dedicated to its testing.
- Gauss 2 trial: Of particular interest is the recent Gauss 2 trial of evolocumab. The phase 3 trial results confirmed the positive findings of previous phase 2 investigations.
Researchers enlisted 308 statin-intolerant participants. Some received evolocumab and others received ezetimibe, a drug that inhibits cholesterol absorption by the small intestines. Evolocumab lowered LDL cholesterol by 53 to 56 percent, as compared to ezetimibe which lowered LDL 17 to 19 percent.
“That is a significant finding”, says the study’s lead investigator Leslie Cho, MD, Director of the Women’s Cardiovascular Center and Section Head, Preventive Cardiology and Rehabilitation, in the Department of Cardiovascular Medicine at Cleveland Clinic. “The results confirm the positive findings from the AMGEN phase 2 trials on statin intolerant patients. In this high risk group, patients who were intolerant to 2 or more statins were able to tolerate PCSK9 without recurrence of myalgia.”
Steven Nissen, MD, Chairman of Cleveland Clinic’s Department of Cardiovascular Medicine, did not participate in the study, but says it is the latest in a series of investigations that increasingly sheds positive light on the potential of PCSK9 –inhibiting medications in LDL cholesterol control. “This is the most powerful LDL-lowering therapy yet discovered. Although we don’t yet know the long-term safety of these drugs, they appear to be safe and effective in patients who can’t tolerate statins,” he said.
- Sanofi-Regeneron trials: Another ongoing investigation sponsored by Sanofi and Regeneron pharmaceuticals, will continue in phase 3 testing of the companies’ fully-human monoclonal antibody that targets PCSK9. The expansive testing of the drug will include multiple studies, over many countries and enlist as many as 220,000 participants.
This study aims to establish the long-term safety of this PCSK9 inhibitor, both as a therapy by itself and as a drug given with other cholesterol-lowering therapies.
Dr. Nissen looks forward to the continued success of PCSK9 trials, “For clinicians like myself … statin intolerance is the bane of our existence. These patients are very hard to treat, and knowing we have a therapy that could potentially be approved in the next few years that can lower LDL by more than 50 percent and be well tolerated without muscle-related side effects is a very big deal.”
PCSK9 inhibitors need more testing to receive regulatory approval, including the successful conclusion of ongoing safety and efficacy trials.
“We are optimistic about the future of PCSK9 inhibitors, but we still need proof of their long-term safety,” says Dr. Cho. “These powerful drugs promise to help high-risk patients for whom statin medication proves intolerable or ineffective. So far, they seem safe to use on a short-term basis, and their ability to lower LDL cholesterol is striking.”