11/12/2023 | Press release | Distributed by Public on 11/12/2023 15:03
Research Highlights:
Embargoed until 3:45 p.m. ET, Sunday, Nov. 12, 2023
PHILADELPHIA, Nov. 12, 2023 - In the first human trial of a new therapeutic, a single injection of lepodisiran reduced levels of lipoprotein(a), or Lp(a), to undetectable levels for nearly one year, according to late-breaking science presented today at the American Heart Association's Scientific Sessions 2023. The meeting, Nov. 11-13, in Philadelphia, is a premier global exchange of the latest scientific advancements, research and evidence-based clinical practice updates in cardiovascular science. The full results and manuscript are simultaneously published today in the Journal of the American Medical Association (JAMA).
Lp(a) is a form of cholesterol that has some characteristics in common with LDL cholesterol (low-density lipoprotein cholesterol, also known as "bad cholesterol"), including causing plaque to build up in arteries and reduce blood flow to the heart, brain, kidneys, legs and other parts of the body. According to the American Heart Association, high Lp(a) levels are inherited from your family, and a high level of Lp(a) is a common independent risk factor for cardiovascular disease.
"If further trials show that this medication - lepodisiran - is safe and can reduce heart attacks and strokes, it would be good news for patients because it eliminates a risk factor we've been unable to treat," said lead study author Steve Nissen, M.D., chief academic officer at the Heart, Vascular & Thoracic Institute at the Cleveland Clinic in Ohio. "This medication could be a once-a-year injection similar to a vaccine for people with high Lp(a) levels."
Lifestyle changes, such as exercise and improved diet, have little impact on Lp(a) levels, and neither do medications that reduce "bad" cholesterol such as statins. Some people with elevated levels of Lp(a) plus other serious conditions, such as genetic disorders that raise bad cholesterol, are sometimes treated with apheresis - a dialysis-like treatment to remove harmful cholesterol from their blood. However, there is no FDA-approved medication targeted at Lp(a).
The medication, lepodisiran, is a small interfering RNA that reduces the production of Lp(a) in the liver by disabling messenger RNA that is involved in producing apolipoprotein(a), a key component in the Lp(a) particle. The medication is attached to a special sugar known as GalNAc, allowing the medication to be carried into liver cells because they have receptors for the sugar. It is also constructed to be chemically resistant to degradation so its effects last longer.
"How do you beat a risk factor that's largely genetic? One highly effective approach is to interfere with the gene, and that's what lepodisiran and other new therapies are designed to do," Nissen said.
In the current study, 48 volunteers with abnormal levels of Lp(a), averaging 110 nmol/L, were given a single subcutaneous injection. Twelve participants were randomly assigned to receive a placebo and 36 participants received lepodisiran. In the lepodisiran group, six participants randomly received different doses of lepodisiran - 4, 12, 32, 96, 304 or 608 mg. The participants were discharged three days after receiving the injection, and follow-up blood tests were done for 48 weeks, just 4 weeks shy of one year.
The study found:
"In our view, this therapeutic is very promising. These data indicate lepodisiran is safe, and its effectiveness at lowering Lp(a) was profound, with near-total elimination of Lp(a) that lasted for a long time. We'll know more after the Phase 2 study, which is underway," Nissen said.
Background:
The ongoing Phase 2 trial is testing the medication in people with both high levels of Lp(a) and a high risk of early heart attack or stroke.
"For now, if you have a strong family history of early heart disease, you should insist on having your Lp(a) measured," Nissen said. "As these therapies become available, you can seek treatment. In the meantime, you can take steps to lower your blood pressure, treat high LDL cholesterol if you have it, eat well and do other things to protect yourself."
"There are several other treatments in development. Our priority should be finding effective treatment options for people with high Lp(a), so their risk of cardiovascular disease can be reduced," Nissen said.
Disclosures are listed in the abstract, and coauthors are listed in the manuscript. The study was funded by Eli Lilly and Company.
Statements and conclusions of studies that are presented at the American Heart Association's scientific meetings are solely those of the study authors and do not necessarily reflect the Association's policy or position. The Association makes no representation or guarantee as to their accuracy or reliability. Abstracts presented at the Association's scientific meetings are not peer-reviewed, rather, they are curated by independent review panels and are considered based on the potential to add to the diversity of scientific issues and views discussed at the meeting. The findings are considered preliminary until published as a full manuscript in a peer-reviewed scientific journal.
The Association receives funding primarily from individuals; foundations and corporations (including pharmaceutical, device manufacturers and other companies) also make donations and fund specific Association programs and events. The Association has strict policies to prevent these relationships from influencing the science content. Revenues from pharmaceutical and biotech companies, device manufacturers and health insurance providers and the Association's overall financial information are available here.
Additional Resources:
About the American Heart Association
The American Heart Association is a relentless force for a world of longer, healthier lives. We are dedicated to ensuring equitable health in all communities. Through collaboration with numerous organizations, and powered by millions of volunteers, we fund innovative research, advocate for the public's health and share lifesaving resources. The Dallas-based organization has been a leading source of health information for nearly a century. Connect with us on heart.org, Facebook, X or by calling 1-800-AHA-USA1.
###
For Media Inquiries and AHA Expert Perspective:
AHA Communications & Media Relations in Dallas: 214-706-1173; [email protected]
Michelle Kirkwood: 703-457-7838; [email protected]
For Public Inquiries: 1-800-AHA-USA1 (242-8721)
heart.org and stroke.org