Merck Licenses HRS-5346 for Cardiovascular Disease from Hengrui
Merck, known as MSD outside of the United States and Canada, and Jiangsu Hengrui Pharmaceuticals Co., Ltd. (“Hengrui Pharma”), a leading global pharmaceutical company with a strong focus on scientific and technological innovation, have announced an exclusive license agreement for HRS-5346. This investigational oral small molecule Lipoprotein(a), or Lp(a), inhibitor is currently being evaluated in a Phase 2 clinical trial in China.
The agreement represents a significant milestone in the field of cardiovascular medicine, as elevated levels of Lp(a) are associated with an increased risk of atherosclerotic cardiovascular disease, which affects a significant portion of the global population.
The Significance of Lipoprotein(a) in Cardiovascular Health
Lipoprotein(a), or Lp(a), is a type of lipoprotein produced in the liver. It functions by carrying cholesterol, fats, and proteins through the bloodstream. Unlike LDL cholesterol, which has long been established as a contributor to atherosclerosis, Lp(a) is also genetically determined. Its elevated levels can accumulate in blood vessel walls, forming plaques that may restrict blood flow and increase the risk of serious cardiovascular conditions, such as heart attacks and strokes. Given that approximately 1.4 billion people worldwide have elevated Lp(a) levels, there is a strong demand for innovative treatments targeting this specific lipoprotein.
Dr. Dean Y. Li, President of Merck Research Laboratories, emphasized the importance of targeting Lp(a) in cardiovascular treatment, stating: “Elevated blood concentrations of Lp(a) provide a well-documented risk factor for atherosclerotic cardiovascular disease, affecting as many as 1 in 5 adults globally. HRS-5346, an investigational oral small molecule inhibitor of Lp(a) formation, is an important addition that expands and complements our cardio-metabolic pipeline.”
Details of the Exclusive License Agreement
Under the terms of this agreement, Hengrui Pharma has granted Merck the exclusive rights to develop, manufacture, and commercialize HRS-5346 globally, with the exception of the Greater China region. In exchange, Hengrui Pharma will receive an upfront payment of $200 million. Additionally, the company is eligible for milestone payments that could total up to $1.77 billion, contingent upon achieving specified development, regulatory, and commercial milestones. If HRS-5346 gains regulatory approval and reaches the market, Hengrui Pharma will also receive royalties based on net sales.
Dr. Frank Jiang, Executive Vice President and Chief Strategy Officer of Hengrui Pharma, expressed confidence in the collaboration: “We are pleased to partner with Merck, a global leader in cardiovascular care. We believe Merck’s clinical expertise and global scale will help accelerate the development of HRS-5346 and potentially provide more patients with an additional option to reduce their risk of atherosclerosis.”
This agreement aligns with Merck’s broader strategy of expanding its portfolio in the cardio-metabolic therapeutic area. By adding HRS-5346 to its pipeline, Merck aims to enhance its ability to address cardiovascular diseases and improve patient outcomes globally.
Market Impact and Financial Considerations
The transaction is expected to close in the second quarter of 2025, pending regulatory approval under the Hart-Scott-Rodino Antitrust Improvements Act and other customary closing conditions. As part of the financial terms, Merck will record a pre-tax charge of $200 million, equivalent to approximately $0.06 per share, in the quarter in which the transaction closes. This charge will be reflected in both GAAP and non-GAAP financial results.
This deal represents a strategic investment for Merck as it aims to strengthen its position in the cardiovascular space. The growing prevalence of cardiovascular disease worldwide has led to an increased demand for innovative treatment options. Given that Lp(a)-lowering therapies are still in the early stages of development, this agreement positions Merck at the forefront of an emerging therapeutic area with significant potential for growth.
The Growing Importance of Lp(a)-Targeted Therapies
Despite significant advances in cardiovascular medicine, there remains a lack of effective treatments specifically targeting elevated Lp(a). Current lipid-lowering therapies, such as statins and PCSK9 inhibitors, primarily focus on reducing LDL cholesterol but do not adequately address Lp(a)-related risks. This has fueled interest in novel therapeutics like HRS-5346, which directly inhibit Lp(a) formation.
Recent research has demonstrated that Lp(a) contributes to cardiovascular disease progression independently of LDL cholesterol. Individuals with high Lp(a) levels often face an increased risk of major adverse cardiovascular events, even when their LDL cholesterol levels are well-managed. Because Lp(a) levels are largely determined by genetics, lifestyle changes alone are insufficient in managing this risk factor. This underscores the need for targeted pharmacological interventions such as HRS-5346.
Currently, no Lp(a)-specific therapies have received regulatory approval, but several investigational drugs, including antisense oligonucleotides and small molecule inhibitors, are in various stages of clinical development. The approval of such therapies could mark a paradigm shift in cardiovascular disease management, potentially reducing the burden of atherosclerosis and its associated complications.
Merck’s Commitment to Cardiovascular Innovation
Merck has a longstanding history of developing cardiovascular treatments. The company has been actively investing in cardio-metabolic research and development, aiming to provide innovative therapies for patients with unmet medical needs. By acquiring the global rights to HRS-5346 (excluding Greater China), Merck reinforces its commitment to advancing cardiovascular care.
This agreement also highlights Merck’s strategy of forging partnerships with leading global pharmaceutical companies to strengthen its pipeline. By collaborating with Hengrui Pharma, Merck gains access to a promising investigational therapy while leveraging its expertise in drug development and commercialization to bring the treatment to a broader patient population.
The Future of HRS-5346
As HRS-5346 progresses through clinical trials, Merck will likely focus on expanding its research efforts beyond China. Given the growing awareness of Lp(a) as a cardiovascular risk factor, there is substantial interest in conducting large-scale clinical studies to evaluate the drug’s efficacy and safety in diverse populations. If successful, HRS-5346 could become one of the first oral therapies specifically designed to lower Lp(a), setting a new standard in cardiovascular disease prevention and management.
With regulatory approval anticipated in the coming years, the partnership between Merck and Hengrui Pharma is poised to have a profound impact on the cardiovascular treatment landscape. Patients at risk for cardiovascular disease due to elevated Lp(a) levels may soon have access to a targeted, effective treatment option that could significantly reduce their risk of major cardiovascular events.
