- An investigational drug called lerodalcibep lowered low-density lipoprotein (LDL) cholesterol, or “bad” cholesterol, by 50% or more, a new study showed.
- The year-long clinical trial included people who were unable to lower their LDL cholesterol enough using statins.
- Lerodalcibep is not yet approved by the FDA, but two other drugs in this class were approved by the agency in 2015.
An investigational drug lowered low-density lipoprotein (LDL) cholesterol, or “bad” cholesterol, in people who were unable to lower their LDL cholesterol enough using statins.
Researchers say the results support the use of lerodalcibep as a treatment for people with existing cardiovascular disease or who are at high or very high risk of cardiovascular disease.
Most people in the study who received once-monthly injections of lerodalcibep were able to reduce their LDL cholesterol level by 50% or more. They also met target levels for LDL cholesterol recommended by current guidelines.
The results of the clinical trial were published July 3 in JAMA Cardiology.
Statins and other cholesterol-lowering meds
Around 10% of American adults have high cholesterol, according to the Centers for Disease Control and Prevention.
However, only about half who could benefit from a cholesterol-lowering medicine are currently taking one, the agency said. This increases their risk of heart attack, stroke and other major cardiovascular problems.
Medications available for treating high cholesterol include statins, which have been available since the 1980s, and the newer PCSK9 inhibitors.
PCSK9 inhibitors target a protein in the liver called proprotein convertase subtilisin kexin 9, or PCSK9.
“PCSK9 inhibitors improve the ability of your liver to take up cholesterol particles from the blood and process them,” said Yu-Ming Ni, MD, cardiologist and lipidologist at MemorialCare Heart and Vascular Institute at Orange Coast Medical Center in Fountain Valley, Calif. “The result is a significant reduction in cholesterol levels.”
The FDA approved two PCSK9 inhibitors in 2015: alirocumab (Praluent) and evolocumab (Repatha). Both are given by injection under skin, every 2 to 4 weeks. Lerodalcibep is not yet approved by the FDA.
“[Approved PCSK9 inhibitors] work really well to lower cholesterol. Sometimes even better than the statins that we typically give for cholesterol lowering,” Ni told Healthline.
Also, “patients don’t get too many side effects from PCSK9 inhibitors,” he said. “The only downside is that they can be a little expensive for some patients, depending on insurance.”
PCSK9 inhibitors may be used for patients who have been unable to lower their cholesterol enough using statins. In this case, a PCSK9 inhibitor would be prescribed alongside a statin.
However, people who can’t tolerate the side effects of statins may take only a PCSK9 inhibitor, said Ni.
Reductions in cholesterol and other lipids
The new study included 922 adults who were taking the highest dose of a statin that they could tolerate, but still hadn’t lowered their LDL cholesterol to the target level recommended by guidelines.
The average age of participants was 65 years and 45% were female. Overall, 88% of people finished the clinical trial.
People were randomly assigned to receive either monthly injections of lerodalcibep or a non-acting placebo for 52 weeks.
After one year, 90% of people who received lerodalcibep reduced their LDL cholesterol by 50% or more, and met the recommended LDL cholesterol targets.
On average, people who received lerodalcibep reduced their LDL cholesterol by 56% after 52 weeks and 69.5% after 60 weeks. They also saw reductions in apolipoprotein B, apolipoprotein(a) and triglycerides.
“This is crucial, as both apolipoprotein B and high lipoprotein(a) levels are a significant risk factor for cardiovascular disease,” said Jacqueline Hollywood, MD, cardiologist with Hackensack University Medical Center, “and we currently have limited treatment options for lipoprotein(a).”
The study results also show that lerodalcibep was well tolerated, with similar adverse events as the placebo.
The main difference was that reactions at the injection site occurred more frequently in people who received lerodalcibep (6.9%) compared to those in the placebo group (0.3%). These reactions were mild or moderate in severity.
Larger, long-term studies needed
Given the benefits of FDA-approved PCSK9 inhibitors, Ni said it is good to see a new drug that works in a similar manner as those.
“In this trial, we can see that lerodalcibep lowers LDL cholesterol by a very similar amount [as those other drugs],” he said.
He pointed out that prior studies of FDA-approved PCSK9 inhibitors show that these drugs can also reduce the risk of cardiovascular events such as heart attack and stroke.
However, he cautions that additional longer-term studies would be needed to show whether lerodalcibep has a similar effect on cardiovascular risk.
“Cholesterol-lowering drugs that were very promising have surprised us before,” said Ni. “So I think it’s really important that we continue on to that next step [of additional studies].”
Hollywood highlighted that one limitation of the study is that it included a relatively small number of participants. In spite of that, people in the study had “a wide range of cardiovascular disease risk factors,” she told Healthline, “suggesting the drug could benefit a diverse population.”
One group that the drug may help are people with atherosclerosis, a condition in which plaques build up in the arteries, which can increase the risk of heart attack and stroke.
By lowering cholesterol and inflammation, the drug may prevent the formation of new plaques, said Hollywood, although additional studies are needed to confirm this potential benefit.
“Overall, the study provides promising evidence for the potential of lerodalcibep in cardiovascular disease treatment,” she said.
Takeaway
In a year-long clinical trial, participants were randomly assigned to receive either the PCSK9 inhibitor lerodalcibep or a non-acting placebo. People in the study were unable to lower their LDL cholesterol, or bad cholesterol, using statins.
The majority of people who received lerodalcibep saw reductions in their LDL cholesterol of 50% or more, and met LDL cholesterol targets set by guidelines.
People who received lerodalcibep also saw reductions in triglycerides and other lipids linked to an increased risk of heart attack and stroke. Lerodalcibep was well tolerated, with similar adverse effects as placebo. The main side effects of the drug were those that occurred at the injection site.
