OCEAN (a)-DOSE extended study of olpasiran
In a separate presentation, Michelle L. O’Donoghue, MD, MPH, reported findings from an extension of the phase 2 trial of olpasiran in patients with atherosclerotic CVD and elevated Lp(a).
courtesy Brigham and Women's Hospital
Dr. Michelle L. O’Donoghue
Olpasiran is a small interfering RNA (siRNA) molecule directed to the liver that prevents the assembly of Lp(a).
Dr. O’Donoghue, from Brigham and Women’s Hospital and Harvard Medical School in Boston, presented the main results from the OCEAN(a) DOSE (TIMI 67) study of olpasiran, at the 2022 annual scientific sessions of the American Heart Association, and the trial was simultaneously published online in the New England Journal of Medicine.
The trial included 281 patients with established atherosclerotic CVD and Lp(a) greater than 150 nmol/L (60 mg/dL). Participants were randomly assigned to one of four doses of olpasiran (10 mg, 75 mg, or 225 mg every 12 weeks, or 225 mg every 24 weeks) or matching placebo, administered subcutaneously.
At 36 weeks, doses of 75 mg or more of olpasiran every 12 weeks led to reductions of more than 95% in levels of Lp(a).
The extension study aimed to examine the effects of olpasiran on levels of the oxidized phospholipids on apolipoprotein B100 (OxPL-apoB) and on levels of Lp(a), as well as safety, after the last administered dose.
The minimum extended off-treatment period was 72 weeks from randomization (in 276 patients). Complete follow-up was a median of 86 weeks (50 weeks after the last administered dose).
The study showed that “olpasiran is an siRNA that robustly lowers Lp(a) levels” and “leads to a marked and durable reduction” in proatherogenic OxPL-apoB, Dr. O’Donoghue reported.
Patients on doses of at least 75 mg every 12 weeks “sustained around a 40%-50% placebo-adjusted reduction in Lp(a) levels close to 1 year after the last dose.”
The long-term clinical efficacy and safety of olpasiran are being further evaluated in the ongoing phase 3 OCEAN(a)-Outcomes trial which has as an estimated enrollment of 6000 and projected completion in December 2026.
These are “exciting” results, and “we’re all waiting with bated breath for more news,” said session cochairperson Louise Bowman, MD, University of Oxford (England).
In reply to questions from the audience, Dr. O’Donoghue said that the only adverse events that were imbalanced during the on-treatment phase were injection-site reactions and localized hypersensitivity reactions, which were not reported during the off-treatment period. There was also no evidence of a proinflammatory increase in phospholipids, or of a rebound effect on Lp(a) levels after stopping olpasiran.
The muvalaplin study was funded by Eli Lilly. Dr. Nicholls reported numerous conflicts of interest with various pharmaceutical companies. Dr. O’Donoghue reported receiving research grants from Amgen, AstraZeneca, Merck, and Novartis; consulting with Amgen and Novartis; and serving as a data and safety monitor for AstraZeneca and Janssen.
A version of this article first appeared on Medscape.com.