One morning at the AmGYM, Amgen's on-site fitness center in Thousand Oaks, a routine workout turned into a medical emergency when Justin Murray's manager suffered a heart attack. Tests revealed his manager had elevated lipoprotein(a), or Lp(a), a silent genetic driver associated with cardiovascular disease.
The event inspired Murray, now a senior director of research at Amgen, to further investigate Lp(a). “At the time, few people, even clinicians, were talking about Lp(a),” Murray recalled. “That experience made heart health and Lp(a) even more personal for me, showing how important it was to raise awareness of this hidden genetic risk factor and making it clear how much work needed to be done.”
Dr. Maria-Laura Monsalvo, an executive medical director at Amgen, recalled similar cases during her time as a cardiologist in Argentina. “Some patients tried to do everything right—control their low-density lipoprotein cholesterol (LDL-C), their blood pressure, their diabetes—and still experienced heart disease. That's when you realize there's another lipoprotein we need to understand.”
The Silent Risk Few Know About
Despite its importance, Lp(a) remains one of the least understood cardiovascular risk factors. This cholesterol-carrying particle contains an added protein, apolipoprotein(a), that affects how it behaves in the bloodstream. Elevated Lp(a) promotes development of vulnerable plaques due to its proatherosclerotic, proinflammatory and prothrombotic properties, and are associated with an increased risk of heart attack and stroke.
Monica Florio, senior director and senior project team leader, has seen firsthand how little awareness exists around Lp(a). “It's genetically determined and largely unaffected by diet or lifestyle. 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.”
Testing adds another layer of complexity. Unlike standard cholesterol checks, Lp(a) isn't part of routine lipid panels, and results can vary depending on whether labs measure mass concentration (mg/dL), which reflects the weight of Lp(a) in the blood, or molar concentration (nmol/L), which reflects the number of Lp(a) particles. Due to genetic variability of its protein component, Lp(a) comes in a variety of sizes with different mass. Molar reports the number of particles, independently of their size or mass, which may provide a clearer picture cardiovascular risk.
“As we learned more about Lp(a), many of us started checking our own levels and quickly saw how hard it was to even get tested,” she said. “It became part of our mission to make Lp(a) screening as common as cholesterol testing.”
Decades of Innovation Position Amgen to Take on Lp(a)
To tackle a genetically-driven risk factor like elevated Lp(a), which cannot be controlled by current lipid-lowering therapies, Amgen collaborated with Arrowhead Pharmaceuticals to license molecules with an innovative type of modality: small interfering RNA, or siRNA.
“We looked at siRNA, which allows us to go directly to the source,” said 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.”
Those pre-clinical insights culminated in olpasiran, Amgen's investigational siRNA designed to reduce Lp(a) production in the liver, currently in phase 3 trials. It represents a new chapter in both Amgen's cardiovascular pipeline and the potential of RNA therapeutics.
Investigating a Potential Option for Patients
From research to regulatory submissions, Amgen's approach to Lp(a) exemplifies what's possible when teams unite around a single goal.
“I'm excited to learn the results of the OCEAN(a)-Outcomes Phase 3 study—a trial designed to test whether lowering elevated Lp(a) levels can reduce major cardiovascular events,” noted Monsalvo. “It's been a huge cross-functional effort across departments working hand-in-hand to better understand the impact of Lp(a) on patients.”
The team also prioritized representation, enrolling participants from South Asian and African American communities disproportionately affected by elevated Lp(a).
Meanwhile, on the regulatory front, Minell Karimi, a senior director in global regulatory affairs, and her colleagues are helping global health authorities understand siRNA therapies and the role of Lp(a) 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.”
A Mission-Driven Promise to Patients
For Amgen, the pursuit of an Lp(a) treatment is as personal as it is scientific. What began as a collection of lab challenges and regulatory puzzles has evolved into a mission that unites discovery scientists, clinicians, and strategists across continents.
The team's motivation remains clear: to shed light on an important yet underrecognized area of cardiology and bring awareness to patients who may not know they have elevated Lp(a).
“We see the excitement at scientific congresses, but in everyday practice, the knowledge gap is real,” said Karimi. “It's up to us to close that gap and help everyone better understand the significant risks of living with elevated Lp(a).”
Murray agreed. “When I share updates with my former manager, it feels like we've come full circle,” he said. “This isn't just about innovation. It's about advancing science in a way that could truly matter for people's lives.”
The message from Amgen's Lp(a) team is simple: ask your doctor about Lp(a) and understand how your Lp(a) level can reduce the risk of heart disease. Awareness drives discovery, and every test, every conversation, brings the scientific community one step closer to closing the Lp(a) knowledge gap.
