A routine workout at the AmGYM, Amgen’s on-site fitness center in Thousand Oaks, California, took a frightening turn when a manager suffered a heart attack. The incident, as recounted by Justin Murray, now a senior director of research at Amgen, wasn’t just a personal scare; it sparked a deeper investigation into a relatively unknown genetic contributor to heart disease: lipoprotein(a), or Lp(a). This experience underscored a critical gap in cardiovascular health awareness and ignited a mission within Amgen to address it.
For Dr. Maria-Laura Monsalvo, an executive medical director at Amgen, the case resonated with observations from her earlier career as a cardiologist in Argentina. She frequently encountered patients who diligently managed known risk factors – cholesterol, blood pressure, diabetes – yet still experienced cardiac events. “That’s when you realize there’s another lipoprotein we need to understand,” she explained. The story of Murray’s manager, and Monsalvo’s past experiences, highlight the limitations of focusing solely on traditional risk factors and the need to explore the role of genetics in cardiovascular health.
Lp(a) is increasingly recognized as a significant, yet often overlooked, piece of the heart disease puzzle. Unlike LDL cholesterol, which is heavily influenced by lifestyle, Lp(a) levels are largely determined by genetics. Approximately one in five people worldwide may have elevated Lp(a) levels without knowing it, according to estimates, because it isn’t routinely tested for. This silent risk factor is now the focus of intense research and, potentially, a new generation of therapies.
Unraveling the Complexity of Lp(a)
Lp(a) isn’t simply another type of cholesterol. It’s a cholesterol-carrying particle distinguished by the presence of apolipoprotein(a), a protein that significantly impacts how the particle behaves within the bloodstream. Elevated levels of Lp(a) are linked to an increased risk of heart attack and stroke due to its proatherosclerotic, proinflammatory, and prothrombotic properties – meaning it promotes plaque buildup, inflammation, and blood clot formation. The American Heart Association recognizes Lp(a) as a genetically determined risk factor for cardiovascular disease, but acknowledges that more research is needed to fully understand its role and optimal management. Learn more about Lp(a) from the American Heart Association.
Monica Florio, a senior director and senior project team leader at Amgen, emphasizes the lack of widespread awareness surrounding Lp(a). “It’s genetically determined and largely unaffected by diet or lifestyle,” she says. “One in five people worldwide could have elevated Lp(a) and never know it, unless they obtain a specific test. Even cardiologists were unfamiliar with it when we started researching.” This lack of awareness extends to testing protocols. Lp(a) isn’t included in standard lipid panels, and interpreting results can be complicated. Labs can measure Lp(a) concentration in milligrams per deciliter (mg/dL) – reflecting the weight of the particle – or nanomoles per liter (nmol/L) – reflecting the number of particles. The molar concentration (nmol/L) is increasingly favored by researchers as it provides a more accurate assessment of cardiovascular risk, independent of particle size.
Amgen’s Pioneering Approach with siRNA
Recognizing the limitations of existing treatments, which primarily target LDL cholesterol, Amgen turned to a novel therapeutic approach: compact interfering RNA, or siRNA. This technology, licensed from Arrowhead Pharmaceuticals, allows scientists to directly target the source of the problem – the gene that produces apolipoprotein(a) in the liver. “We looked at siRNA, which allows us to go directly to the source,” explained Murray. “It silences the gene that produces apolipoprotein(a) in liver cells, preventing excess Lp(a) production. For a scientist, it’s extraordinary to see how fast we can move from discovery to proof of concept.”
This research has led to the development of olpasiran, Amgen’s investigational siRNA, currently undergoing phase 3 clinical trials. Olpasiran is designed to reduce the production of Lp(a) in the liver, offering a potentially groundbreaking treatment for individuals with genetically elevated levels. The development of olpasiran represents a significant advancement in both Amgen’s cardiovascular pipeline and the broader field of RNA therapeutics, which harnesses the power of RNA to treat disease.
The OCEAN(a)-Outcomes Trial and a Focus on Diversity
Amgen’s commitment extends beyond scientific innovation to encompass a dedication to inclusive research. The ongoing OCEAN(a)-Outcomes Phase 3 study, designed to evaluate whether lowering Lp(a) levels can reduce major cardiovascular events, is specifically enrolling participants from South Asian and African American communities, populations known to be disproportionately affected by elevated Lp(a). “It’s been a huge cross-functional effort across departments working hand-in-hand to better understand the impact of Lp(a) on patients,” noted Monsalvo. This focus on diversity aims to ensure that the benefits of potential new treatments are accessible to all who need them.
Simultaneously, Amgen’s regulatory affairs team, led by Minell Karimi, a senior director in global regulatory affairs, is working to educate global health authorities about the science of Lp(a) and the rationale for targeting it as an independent risk factor. “We’re engaging with regulatory authorities to discuss the science around Lp(a) as a genetically-driven risk factor for cardiovascular events, and the rationale for lowering it in the context of the olpasiran development program.” This proactive engagement is crucial for securing regulatory approval and ensuring that olpasiran, if proven effective, can reach patients quickly.
The pursuit of an Lp(a) treatment at Amgen is driven by a deeply personal mission. As Murray reflects, sharing updates with his former manager – the individual whose heart attack sparked this journey – brings the work full circle. “This isn’t just about innovation. It’s about advancing science in a way that could truly matter for people’s lives.”
Amgen encourages individuals to discuss Lp(a) testing with their healthcare providers and to understand their individual risk factors for heart disease. Increased awareness and early detection are key to preventing cardiovascular events. The team’s message is clear: understanding your Lp(a) level is a proactive step towards protecting your heart health.
Disclaimer: This article provides information for general knowledge and informational purposes only, and does not constitute medical advice. It is essential to consult with a qualified healthcare professional for any health concerns or before making any decisions related to your health or treatment.
The next major milestone in this research is the anticipated release of data from the OCEAN(a)-Outcomes Phase 3 study. These results will be critical in determining the efficacy and safety of olpasiran and its potential to transform the treatment of cardiovascular disease. Share your thoughts and questions in the comments below.
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