Amgen Presents Data from Phase 2 OCEAN(a)-DOSE study of olpasiran

Amgen (NASDAQ: AMGN ) today announced data from the final analysis of the Phase 2 OCEAN(a)-DOSE study of olpasiran, a small interfering RNA (siRNA) during the Late-Breaking Science Session at the European Society of Cardiology (ESC) Annual Meeting being held in Amsterdam. In the off-treatment extension period, olpasiran showed a lasting effect on Lp(a) reduction nearly a year after the last dose.

Results from the OCEAN(a)-DOSE Phase 2 study announced in November of 2022 showed that doses of olpasiran ≥75 mg Q12W reduced patients' Lp(a) by >95% at week 36. The results from the off-treatment extension period show that patients previously dosed with ≥75 mg of olpasiran sustained a ~40-50% placebo-adjusted percent reduction in Lp(a) nearly a year after the last dose. No new safety concerns were identified during the off-treatment extension period.

"We are dedicated to reducing LDL cholesterol levels in people globally and continuing to pioneer ways to address the greatest risk factors in cardiovascular disease, including Lp(a). Worldwide, millions of people are at an increased risk of cardiovascular events due to elevated Lp(a) levels. Unfortunately, there are no approved medicines," said Paul Burton, senior vice president and chief medical officer at Amgen. "Data from the off-treatment extension period provide additional evidence of olpasiran's lasting effect in reducing Lp(a) levels. We are quickly advancing the Phase 3 cardiovascular outcome trial."

Additionally, this study was the first to explore the effects of olpasiran on a key biomarker strongly associated with atherosclerosis, pro-atherogenic OxPL-apoB [Oxidized Phospholipids (Ox-PL) on apoB-100 (apoB)]. During the treatment period, olpasiran showed a dose-dependent reduction in pro-atherogenic OxPL-apoB.

"Additional results from the OCEAN(a)-DOSE study continue to be encouraging, as they tell us olpasiran not only robustly reduces Lp(a) levels, but that it has a long-lasting effect on this important risk factor for ASCVD," said Michelle L. O'Donoghue, MD, MPH, associate professor, Harvard Medical School, Cardiovascular Medicine and lead investigator of the OCEAN(a)-DOSE study. "Additionally, we were able to show that olpasiran reduced OxPL-apoB, further adding to the potential of RNA interference with olpasiran as a promising treatment approach to reducing elevated Lp(a)."

LDL Awareness to Action Implementation Consortium

Amgen is committed to working with stakeholders to achieve the goal of reducing cardiovascular disease globally and, this year at ESC, convened a new LDL Awareness to Action Implementation Consortium (LATAIC). LATAIC is focused on improving LDL-C testing and evidence-based treatment through identification of opportunities to accelerate efficiency and impact of the translation of evidence-based research into clinical practice. The consortium is comprised of leading CV institutions, including Duke, Harvard's BAIM Institute, Johns Hopkins, Geisinger, University of Colorado, St. Luke's, Brigham and Women's Hospital, Providence, Yale and UT Southwestern.

"I am proud to be working alongside Amgen and other cross disciplinary leaders in the cardiovascular space to increase LDL-C testing and implementation of evidence-based treatment, in order to tackle the urgent public health crisis of cardiovascular disease," said C. Michael Gibson, M.D., chief executive officer at the non-profit BAIM Institute of Clinical Research, and professor of medicine, Harvard. "We hope to enable scalable action to address unmet LDL needs, drive efficiency, and improve quality of care for patients by expanding LATAIC to include other CVD industry stakeholders."

For more information about the ESC abstracts, see below.

Amgen Abstracts

• RNA inhibition of Lp(a) with Olpasiran: Effects on Oxidized Phospholipids and Primary Results of the OCEAN(a)-DOSE Extension Program on Long-Term Efficacy and Safety
  Late-breaker, Saturday, Aug. 26, 4:45-5:00 pm CEST
• Cardiovascular Outcomes in Patients with Coronary Artery Disease and Elevated Lipoprotein(a): Implications for the OCEAN(a)-Outcomes Trial Population.
  Oral Presentation, Sunday, Aug. 27, 10:55-11:05 am CEST
• Characteristics of patients initiating PCSK9i mAb following myocardial infarction and comparability of treatment groups in the Netherlands.
  Moderated poster, Monday, Aug. 28, 2:15-3:00 pm CEST
• Improving risk stratification of recurrent myocardial infarction in a large real-world dataset using machine learning.
  Moderated poster, Saturday, Aug. 26, 11:15-12:00 pm CEST

Investigator-Sponsored Studies (ISS)

• Randomised trial of cholesterol lowering with EVOLocumab to prevent cardiac allograft Vasculopathy in De-novo heart transplant recipients.
  Late-breaker, Monday, Aug. 28, 11:30-11:45 am CEST
• Effect of evolocumab on platelet function in patients with acute coronary syndromes: An analysis of the randomized, double-blind, placebo-controlled EVOPACS Trial.
  Moderated poster, Monday, Aug. 28, 5:15-6:00 pm CEST
• PCSK9 inhibition with evolocumab decreases myocardial inflammation in individuals with acute coronary syndrome [EVACS data].
  Oral presentation, Saturday, Aug. 26, 2:00-2:10 pm CEST
• Lipoprotein(a) and the risk of Major Adverse Limb Events in Patients with Stable Atherosclerotic Vascular Disease [FOURIER/no evo data].
  Moderated poster, Saturday, Aug. 26, 11:15-12:00 pm CEST