The Ocean(a)-DOSE trial made a splash at AHA this year, providing new insight into olpasiran’s potential to reduce Lp(a) levels in patients with ASCVD. In the phase 2 trial, 75 mg or more of the Amgen siRNA therapy delivered at least every three months basically obliterated Lp(a) levels.
There is currently no FDA-approved therapy for reducing Lp(a), despite a large body of evidence linking high levels of the cholesterol-carrying lipoprotein to ASCVD. And because Lp(a) levels are almost entirely genetic (as opposed to being dictated by lifestyle choices), pharmaceutical companies are eager to develop a remedy. Olpasiran is now one of only a handful of drugs in development that fit the bill.
In the study, researchers randomized 281 people with ASCVD and high Lp(a) serum levels to receive one of four doses of olpasiran:
- 10 mg every 12 weeks
- 75 mg every 12 weeks
- 225 mg every 12 weeks
- 225 mg every 24 weeks
At 36 weeks, the Lp(a) concentration had increased by 3.6% in the placebo group, while Lp(a) levels were almost eliminated in the olpasiran group:
- 10 mg every 12 weeks – Lp(a) decreased by 70.5%
- 75 mg every 12 weeks – Lp(a) decreased by 97.4%
- 225 mg every 12 weeks – Lp(a) decreased by 101.1%
- 225 mg every 24 weeks – Lp(a) decreased by 100.5%
The drug is safe, too. The incidence of adverse events was similar across trial groups and to placebo, with the most common olpasiran-related adverse event being mild injection site reaction.
This is a key milestone following Amgen’s acquisition of olpasiran in 2020 from Arrowhead Pharmaceuticals. Armed with these encouraging phase 2 results, Amgen plans to launch a 6k person phase 3 pivotal trial this December.
Phase 2 trial results suggest Amgen’s experimental siRNA therapeutic olpasiran is safe and leads to “profound and sustained” Lp(a) reductions in people with ASCVD. The findings provide a strong foundation for Amgen’s phase 3 testing, scheduled to begin later this year.