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Promising Emergent Therapies for Lowering Lp(a), with Michelle O’Donoghue, MD, MPH

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In an interview O’Donoghue talked about emerging RNA therapies for Lp(a) in phase 2 and 3 trials.

At the Family Heart Global Summit 2024 in Dallas, Texas, Michelle O’Donoghue, MD, MPH, from Brigham and Women’s Hospital, presented the session, “The Future Looks Bright: Emerging Treatments for Lipoprotein(a),” on Monday, August 23, 2024.

HCPLive spoke with O’Donoghue at the summit, who discussed numerous currently developing treatments for Lp(a).

“There are many different therapies that are currently developing, so it's a very exciting field right now,” O’Donoghue said.

Many of the treatments in development are designed to target RNA, the molecule responsible for producing specific proteins. One example is antisense oligonucleotides (ASOs), such as pelacarsen, which bind to the RNA that codes for apolipoprotein, a lipoprotein component. By targeting this RNA, the therapy promotes its breakdown, reducing the production of harmful proteins contributing to conditions like cardiovascular disease.

Other treatments in development are small interfering RNA therapies. These are similar to RNA-directed therapies but have longer durations of action. The RNA therapies are still being evaluated in phase 2 and phase 3 trials, with phase 3 trials on pelacarsen and olpasiran expected to read out in 2025.

O’Donoghue said an unanswered question is how these results will translate into clinical outcomes.

“That's the important question,” she said. “And so, we really need the results of large phase 3 clinical trials to inform us about the efficacy as well as the definitive safety of these therapies.”

Many patients get panicked when they learn they have a high Lp(a) value, especially since it is primarily genetically determined.

“Right now, we don't have effective therapies to lower it, and so we really have been taking just a strategy of traditional risk factor mitigation,” O’Donoghue said. “So ultimately, if these therapies are shown to be effective, it's going to be a very exciting time.”

Relevant disclosures for O'Donoghue include Amgen, Novartis, Janssen, Novo Nordisk, and others.

References

O’Donoghue, M. The Future Looks Bright: Emerging Treatments for Lipoprotein(a). The Family Heart Global Summit 2024 on September 23, 2024, in Dallas, TX.


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