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What's Next for Lipoprotein(a) Lowering Agent SLN360

Steve Nissen, MD, reviews the promising phase 1 APOLLO findings, and details what needs to be investigated next for the siRNA.

New phase 1 APOLLO trial data presented at the American College of Cardiology (ACC) 2022 Scientific Sessions this weekend showed short interfering RNA (siRNA) agent SLN360 provided significant and sustained reduction of lipoprotein(a) (Lp[a]) in patients with inherently greater levels.

The findings, presented by Steve E. Nissen, MD, of the Cleveland Clinic Center for Clinical Research, prelude later-stage assessment of SLN360, which is among a trio of investigative drugs seeking novel use for lowering Lp(a)—a chief biomarker for cardiovascular risk.

In an interview with HCPLive at ACC 2022, Nissen discussed the untreated rate of elevated Lp(a) among a global population: about 1 in every 5 people.

“That’s 64 million people in the US and it’s 1.4 billion people on the planet,” Nissen said. “It’s a common disorder, it’s not been treatable, it’s now becoming treatable, and if it’s true that lowering levels can reduce risk, then this will be a major advance in the treatment of patients.”

Nissen discussed the observed benefit of niacin and regulated PCSK9 inhibitors for Lp(a) lowering; however, no agent is currently available that directly targets the biomarker.

“Historically, we had nothing,” Nissen said. “There’s 3 drugs in development: this is one of them, another one that’s in phase 3 used a different strategy, and there’s another one that’s a short-interfering RNA. So that’s 3 shots on goal. We hope that 1 of them ends up in the back of the net—maybe more than 1 of them.”

Regarding the phase 1 findings for SLN360, Nissen praised the durable benefit observed with the 2 highest doses of the siRNA. But further and greater assessment is necessary.

“We need more work on safety, we need to give multiple doses and see how they affect plasma levels,” he said. “Finally, we have to show that lowering Lp(a) will prevent cardiovascular events or progression of aortic stenosis. That remains to be determined.”