Understanding Lp(a): A Hidden Genetic Risk Factor for Heart Disease

A routine workout at Amgen’s on-site fitness center led to a startling discovery for one manager: elevated lipoprotein(a), or Lp(a). This finding sparked a deeper investigation by Amgen researchers into this often-overlooked genetic contributor to cardiovascular disease.

The Silent Risk Few Know About

Despite its significance, Lp(a) remains one of the least understood cardiovascular risk factors. This cholesterol-carrying particle includes apolipoprotein(a), influencing its behavior in the bloodstream. Elevated Lp(a) promotes the development of vulnerable plaques and is associated with an increased risk of heart attack, and stroke. Approximately one in five people worldwide may have elevated Lp(a) without knowing it, unless specifically tested.

Testing for Lp(a) can be complex. Unlike standard cholesterol checks, it’s not part of routine lipid panels. Results can vary depending on whether labs measure mass concentration (mg/dL) or molar concentration (nmol/L). Molar concentration, which reflects the number of Lp(a) particles, may provide a clearer picture of cardiovascular risk due to genetic variability in the protein component and differing particle sizes.

Decades of Innovation Position Amgen to Take on Lp(a)

To address this genetically-driven risk factor, Amgen collaborated with Arrowhead Pharmaceuticals to license molecules utilizing small interfering RNA (siRNA). This innovative approach targets the source of the problem.

“We looked at siRNA, which allows us to go directly to the source,” said Justin Murray, senior director of research at Amgen. “It silences the gene that produces apolipoprotein(a) in liver cells, preventing excess Lp(a) production.”

This research has culminated in olpasiran, Amgen’s investigational siRNA designed to reduce Lp(a) production in the liver, currently in phase 3 trials.

Investigating a Potential Option for Patients

Amgen’s approach to Lp(a) exemplifies collaboration across departments. The OCEAN(a)-Outcomes Phase 3 study is designed to test whether lowering elevated Lp(a) levels can reduce major cardiovascular events.

The study prioritizes representation, enrolling participants from South Asian and African American communities disproportionately affected by elevated Lp(a). Regulatory teams are also working to educate global health authorities about siRNA therapies and the role of Lp(a) as an independent risk factor.

A Mission-Driven Promise to Patients

For Amgen, the pursuit of an Lp(a) treatment is both scientific and personal. The team’s motivation is to increase awareness of Lp(a) and provide options for patients who may be unaware of their risk.

“We see the excitement at scientific congresses, but in everyday practice, the knowledge gap is real,” said Minell Karimi, a senior director in global regulatory affairs. “It’s up to us to close that gap and assist everyone better understand the significant risks of living with elevated Lp(a).”

As Justin Murray noted, sharing updates with his former manager, who initially inspired the research, highlights the potential impact of this work.

The message from Amgen’s Lp(a) team is clear: 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 and conversation brings the scientific community closer to closing the Lp(a) knowledge gap.