- A new study shows that an experimental drug called Lerodarcibe lowers low-density lipoprotein (LDL) cholesterol, the so-called “bad” cholesterol, by more than 50 percent.
- The year-long clinical trial included people whose LDL cholesterol had not been sufficiently lowered by statins.
- Lerodarcibep has not yet been approved by the FDA, but the other two drugs in this class were approved by the FDA in 2015.
The investigational drug lowered low-density lipoprotein (LDL) cholesterol, or “bad” cholesterol, in people whose LDL cholesterol had not been sufficiently lowered by using statins.
The researchers say the results support the use of lelodarcibe as a treatment for people who already have cardiovascular disease or who are at high or very high risk of cardiovascular disease.
Most study participants who received monthly Lelodarcibe injections were able to lower their LDL cholesterol levels by 50% or more and also achieved the LDL cholesterol goals recommended by current guidelines.
The results of the clinical trial were announced on July 3rd.
About 10% of American adults have high cholesterol.
But only about half of people who could benefit from cholesterol-lowering drugs are currently taking them, the agency said — increasing their risk of heart attack, stroke and other serious cardiovascular events.
Medications available to treat high cholesterol include statins, which have been around since the 1980s, and the relatively new PCSK9 inhibitors.
PCSK9 inhibitors target a protein in the liver called proprotein convertase subtilisin kexin 9 (PCSK9).
“PCSK9 inhibitors improve the liver’s ability to absorb and process cholesterol particles from the blood,” Ni Yuming, M.D.“The result was a significant reduction in cholesterol levels,” says Jonathan Myers, a cardiologist and lipidologist at MemorialCare Heart and Vascular Institute, Orange Coast Medical Center in Fountain Valley, California.
The FDA
“[Approved PCSK9 inhibitors] “It works really well to lower cholesterol, and in some cases it works better than the statins that are typically given to lower cholesterol,” Ni told Healthline.
Also, “patients don’t experience as many side effects from PCSK9 inhibitors,” he says. “The only drawback is that the cost can be a little bit higher for some patients depending on their insurance.”
PCSK9 inhibitors may be used in patients whose cholesterol has not been adequately lowered with statins. In these cases, PCSK9 inhibitors are prescribed in conjunction with a statin.
But people who cannot tolerate the side effects of statins may choose to take PCSK9 inhibitors alone, Ni said.
The new study included 922 adults who were taking the maximum dose of statins they could tolerate but who were unable to lower their LDL cholesterol to the guideline-recommended targets.
The average age of participants was 65 years old, and 45% were women. Overall, 88% completed the study.
Subjects were randomly assigned to receive monthly Lelodarcibep injections or a non-active placebo for 52 weeks.
After one year, 90% of people receiving Lerodarcibep had reduced their LDL cholesterol by 50% or more and met the recommended LDL cholesterol goal.
On average, people who received Lerodarcibep saw a 56% reduction in LDL cholesterol after 52 weeks and a 69.5% reduction after 60 weeks. They also saw reductions in apolipoprotein B, apolipoprotein(a), and triglycerides.
“This is very important because both apolipoprotein B and high lipoprotein(a) levels are significant risk factors for cardiovascular disease,” he said. Jacqueline Hollywood, MD“Currently, there are limited treatment options for lipoprotein(a),” says the cardiologist at Hackensack University Medical Center.
Study results showed that lelodarcibe was well tolerated, with adverse events similar to placebo.
The main difference was that injection site reactions occurred more frequently in the lelodarcibe group (6.9%) compared with the placebo group (0.3%). These reactions were mild or moderate in severity.
Given the benefits of FDA-approved PCSK9 inhibitors, it’s good to see new drugs with similar effects coming out, Ni said.
“This study found that lelodalcibep lowered LDL cholesterol by about the same amount. [as those other drugs],” He said.
He noted that previous studies of FDA-approved PCSK9 inhibitors have shown that these drugs can also reduce the risk of cardiovascular events such as heart attack and stroke.
However, they caution that further, longer studies are needed to show whether lerodarcibe has a similar effect on cardiovascular disease risk.
“Cholesterol-lowering drugs have surprised us before because they seemed very promising,” Ni says, “so I think it’s really important to take the next step.” [of additional studies].”
Hollywood highlighted the study’s relatively small number of participants as a limitation. Nonetheless, study participants “had a range of risk factors for cardiovascular disease,” she told Healthline, “suggesting that this drug may benefit a diverse population.”
One group that the drug may benefit are people with atherosclerosis, a condition in which plaque builds up in the arteries and can increase the risk of heart attack or stroke.
Hollywood said the drug may prevent new plaque from forming by lowering cholesterol and inflammation, but more research is needed to confirm this potential benefit.
“Overall, this study provides encouraging evidence that lerodarcibe may be effective in treating cardiovascular disease,” she said.
In a year-long clinical trial, participants were randomly assigned to receive either the PCSK9 inhibitor lelodarcibe or a non-active placebo. People taking the study had been unable to lower their LDL cholesterol, or “bad” cholesterol, even with statins.
The majority of people receiving Lerodarcibe experienced a 50% or greater reduction in LDL cholesterol and achieved guideline-established LDL cholesterol goals.
People who received Lerodarcibep also had lower triglycerides and other lipids that are associated with an increased risk of heart attack and stroke. Lerodarcibep was well tolerated, and side effects were similar to those of placebo. The drug’s main side effects occurred at the injection site.
