lipoprotein Disorder

In Phase 2 ALPACA results, lepodisiran significantly reduced levels of genetically inherited cardiovascular risk factor, with some patients sustaining reductions for nearly 1.5 years These data were presented at the American College of Cardiology 2025 Scientific Sessions and simultaneously published in the New England Journal of Medicine (NEJM) INDIANAPOLIS, IN, USA I March 30, 2025 I Eli Lilly and Company (NYSE: LLY) today announced positive Phase 2 results for lepodisiran, an investigational small interfering RNA (siRNA) therapy designed to lower the production of lipoprotein(a) [Lp(a)], a genetically inherited risk factor for heart disease. In the Phase 2 ALPACA study, lepodisiran significantly reduced Lp(a) levels by an average of 93.9% over the 60 to 180-day period after treatment with the highest tested dose (400 mg), meeting the primary endpoint. i Participants who received the 16 mg and 96 mg lepodisiran doses experienced a 40.8% reduction and a 75.2% reduction in Lp(a) levels over the same time period, respectively. i Lepodisiran also met additional secondary endpoints, showing reductions in Lp(a) levels following one or two administrations of each of the three tested doses across all timepoints assessed throughout the nearly 18-month-long study. ii Lepodisiran was administered twice at each dose (16 mg, 96 mg, or 400 mg), once at baseline and at day 180, with a separate group receiving 400 mg at baseline and placebo at day 180. The effect of additional doses of lepodisiran remains undetermined. “Nearly a quarter of the world’s population has elevated levels of Lp(a), putting them at a significantly higher risk of cardiovascular events such as heart attacks and strokes. Unfortunately, there are no approved cholesterol-lowering therapies specifically for this genetic risk factor, and lifestyle changes like diet and exercise do not provide meaningful reductions,” said Steven Nissen, M.D., chief academic officer of the Heart, Vascular & Thoracic Institute at the Cleveland Clinic. “These significant and sustained Lp(a) reductions are encouraging and suggest that siRNA approaches like lepodisiran could potentially offer durable benefits with long-term dosing.” About 20% of Americans have high levels of Lp(a), which increases their risk of cardiovascular disease. 1,2 Elevated Lp(a) levels can double or even triple the risk of a heart attack and are associated with other cardiovascular issues such as stroke and heart valve narrowing (aortic valve stenosis). 3,4,5 Lepodisiran is an investigational siRNA therapy designed to reduce levels of Lp(a) by inhibiting the production of apolipoprotein(a) (apo[a]), a key component of Lp(a). “Reducing the inherited cardiovascular risk for patients with high Lp(a) has long been a critically unmet need. These results offer hope for a long-term, durable treatment option,” said Ruth Gimeno, group vice president, diabetes, obesity and cardiometabolic research at Lilly. “These data underscore Lilly’s commitment to advancing genetic medicine to address one of the world’s most pressing healthcare challenges. We will continue to evaluate the potential benefits of lepodisiran in the ongoing Phase 3 cardiovascular outcomes trial.” Results from additional secondary endpoints showed: Treatment-emergent adverse events (TEAEs) related to the study drug occurred in 1% (1/69) of the placebo group, 3% (1/36) of the 16 mg group, 12% (9/74) of the 96 mg group and 14% (20/141) of the pooled 400 mg group. There were no serious adverse events related to lepodisiran treatment. A single death occurred in the 16 mg dose group due to complications of chronic coronary disease. One participant in the placebo group was withdrawn from the study drug due to a TEAE; however, no participants receiving lepodisiran experienced a TEAE leading to withdrawal from treatment or the study. The ACCLAIM-Lp(a) Phase 3 clinical development program, investigating the effect of lepodisiran on the reduction of cardiovascular events in adults with elevated Lp(a), is currently enrolling. About ALPACA ALPACA was a randomized, double-blind, placebo-controlled Phase 2 study designed to investigate the efficacy and safety of lepodisiran in adults with elevated Lp(a). A total of 320 participants were randomized to receive either placebo or one of three doses of lepodisiran (16 mg, 96 mg, or 400 mg) both at baseline and day 180. An additional group received 400 mg of lepodisiran at baseline and placebo at day 180. Results from the two groups receiving 400 mg of lepodisiran were pooled for the primary analysis. The primary endpoint was placebo-adjusted, time-averaged percent change in Lp(a) serum concentration from day 60 to 180. About Lilly Lilly is a medicine company turning science into healing to make life better for people around the world. We’ve been pioneering life-changing discoveries for nearly 150 years, and today our medicines help tens of millions of people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world’s most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer’s disease; providing solutions to some of the most debilitating immune system disorders; and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we’re motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visit Lilly.com and Lilly.com/news , or follow us on Facebook , Instagram , and LinkedIn . P-LLY Trademarks and Trade Names All trademarks or trade names referred to in this press release are the property of the company, or, to the extent trademarks or trade names belonging to other companies are references in this press release, the property of their respective owners. Solely for convenience, the trademarks and trade names in this press release are referred to without the ® and ™ symbols, but such references should not be construed as any indicator that the company or, to the extent applicable, their respective owners will not assert, to the fullest extent under applicable law, the company’s or their rights thereto. We do not intend the use or display of other companies’ trademarks and trade names to imply a relationship with, or endorsement or sponsorship of us by, any other companies. i Placebo-adjusted values based on the treatment-regimen estimand. ii Placebo-adjusted values based on the efficacy estimand, which represents efficacy prior to discontinuation of study drug or initiation of medications known to affect lipoprotein(a). References SOURCE: Ell Lilly

THE WOODLANDS, Texas and REGENSBURG, Germany, July 25, 2023 /PRNewswire/ -- The US Food and Drug Administration has cleared a Numares Health test, the AXINON® LDL-p Test System, as a new tool physicians can use to measure lipoproteins for patients at risk for cardiovascular disease. Currently, Numares is the only company in the US selling an FDA-cleared NMR test. Continue Reading The US Food and Drug Administration has cleared a Numares Health test, the AXINON® LDL-p Test System Tweet this Numares Health AXINON® System — Now FDA-Cleared The FDA clearance also includes the company's core technology platform, the proprietary AXINON® System, that incorporates diagnostic testing algorithms into nuclear magnetic resonance (NMR) spectroscopy. Numares uses this technology to develop diagnostic tests for chronic heart, kidney and liver diseases. This FDA clearance of the AXINON® technology provides a pathway for more rapid FDA clearance of other tests currently in development. A second Numares assay is expected to gain FDA 510(k) clearance later this year, the AXINON® GFR(NMR) kidney function assay. Numares is a health care diagnostics company that develops improved diagnostic testing for conditions related to metabolic dysfunction, such as chronic kidney, liver and cardiac diseases. From a single blood sample, Numares quantifies multiple biomarkers — known and newly discovered. Machine learning then identifies the few, specific metabolites relevant to diagnosis. The newly cleared AXINON® LDL-p Test System provides more detailed information about cardiac function than the standard LDL-C (low-density lipoprotein or "bad cholesterol") measurement. In a joint statement by the American College of Cardiologists and the American Diabetes Association, LDL-p measurements, like those measured by the Numares AXINON® LDL-p Test System, can help physicians in managing patients with elevated risk of cardiovascular disease, because these measurements may better reflect the true cardiac risk associated with cardiometabolic risk. El Harchaoui, et al* reported stronger association of LDL-p and future event of coronary artery disease compared to LDL-C. The consensus report stated that standard cholesterol measurement may not accurately reflect actual cardiac risk, especially in patients with cardiometabolic risk. Patients with cardiometabolic risk include those with prediabetes, abdominal obesity, abnormally high lipid levels and elevated triglycerides. FDA-cleared AXINON® System More than 3 million tests run using AXINON® Innovative testing modality: Uses distinct, transparent algorithms to combine and quantify multiple biomarkers Specific biomarker measurement: Key tool physicians can use to in managing lipoprotein disorders associated with cardiovascular diseases, including atherosclerosis Automated: Runs hundreds of samples a day with just one hour of lab employee time Heart disease in the US (source, US Centers for Disease Control and Prevention) Incidence: Heart disease is the leading cause of death in the US Mortality: One person dies every 33 seconds from cardiovascular disease. About 695,000 people in the US died from heart disease in 2021 — one in every five deaths Health care costs: Heart disease cost about $239.9 billion per year (2018 to 2019). This includes the cost of health care services, medicines and lost productivity due to death. *El Harchaoui, K., et al. Value of low-density lipoprotein particle number and size as predictors of coronary artery disease in apparently healthy men and women: The EPIC-Norfolk Prospective Population Study. J Am Coll Cardiol, 2007. 49(5): p. 547-53. numares.com #precisiondiagnostics #diagnostictesting #biomarkers #NMRmetabolomics #innovation #cardiovascular #CAD #heartdisease #FDAclearance #FDA #CKD #kidneyfunction #HCC #liverdisease About Numares Health Numares Health is a health care company using AI-enabled technology to develop novel diagnostics for conditions stemming from metabolic dysfunction, including chronic kidney, cardiovascular and liver diseases. Numares develops advanced tests for diagnosis and measurement of disease progression by applying machine learning to metabolomics, evaluating multiple biomarkers alone and in combination. The company developed the FDA-cleared AXINON® System that makes next-generation use of nuclear magnetic resonance spectroscopy for this biomarker evaluation. Contact: Alison Ruffin, Numares Health, [email protected] or 770.310.6313 SOURCE Numares Health

Jonathan Weiss/Shutterstock This is the second IND to come out of the two companies’ collaboration. They will initiate a Phase I trial of the drug in cardiometabolic diseases. Jonathan Weiss/Shutterstock Dicerna , based in Lexington, Massachusetts, is having a massive week, with two major announcements. Today, the U.S. Food and Drug Administration (FDA) accepted Dicerna Pharmaceuticals and Eli Lilly and Company ’s Investigational New Drug (IND) application for LY3819469. They will initiate a Phase I trial of the drug in cardiometabolic diseases. This is the second IND to come out of the two companies’ collaboration. In November 2020, the FDA granted their IND for LY3561774 for an undisclosed cardiometabolic disease. The global licensing and research collaboration was entered in 2018 and focused on discovering, developing, and commercializing potential drugs for cardiometabolic disease, neurodegeneration, and pain. They are leveraging Dicerna’s proprietary RNA interference (RNAi) technology platforms. Under the deal, Dicerna is eligible for up to $350 million in development and commercialization milestones for each GalXC hepatocyte target and $355 million for each non-hepatocyte target. Dicerna is also eligible for mid-single-digit to low double-digit tiered royalties on any commercialized products. Today’s announcement triggered a $10 million payment to Dicerna. LY3819469 targets the LPA gene. The protein encoded by this gene is a serine proteinase that inhibits the activity of tissue-type plasminogen activator I. Although the companies have not specified the indications they are investigating, the LPA gene is implicated in various lipoprotein disorders, including familial hyperlipidemia, hyperlipoproteinemia, type III, peripheral vascular disease, and aortic atherosclerosis. Instead of targeting proteins after they have been produced by the body, which is how most drugs work, RNAi silences the genes by destroying specific messenger RNA (mRNA) made from the gene. The protein targeted is never created. “This milestone marks the second IND generated through our productive collaboration with Lilly,” said Bob D. Brown, chief scientific officer and executive vice president of R&D at Dicerna. “In addition to the two candidates now at clinical stage, there are so far, nine discovery research programs connected to this alliance, emphasizing Dicerna’s and Lilly’s shared commitment to bringing forward new RNAi-based therapies to treat a broad range of diseases.” On May 24, Dicerna announced that Boehringer Ingelheim had accepted a GalXC RNAi candidate for advancement under the two companies’ agreements for chronic liver diseases. The candidate is dubbed DCR-LIV2 and will be studied for nonalcoholic steatohepatitis (NASH). NASH is a fatty liver disease in people who drink little or no alcohol and can lead to cirrhosis. It is an area of high unmet need and is associated with the obesity and type 2 diabetes epidemic. The Boehringer-Ingelheim deal also has milestones attached, up to $170 million in additional biobucks related to DCR-LIV2, as well as mid-single-digit royalties. The announcement on the May 24 triggered a single-digit multimillion-dollar preclinical milestone to Dicerna. “Advancing this selected target to development demonstrates the commitment of our team and our collaborative partners at Boehringer Ingelheim to discovering new and innovative ways to treat NASH using RNAi,” said Brown. “Dicerna’s GalXC technology is the ideal platform for this vital work. What’s more, the announcement marks an important milestone for Dicerna and highlights the productivity of our RNAi discovery research engine, as all of Dicerna’s discovery-oriented collaborations have now produced GalXC-based development candidates that are advancing toward the clinic or have already entered clinical development.”