Cardiovascular RNA drugs and oral lipid lowering

• ClinicalTrials.gov lists 237 ¹ interventional studies of the siRNA, antisense and oral lipid drugs in this track; 90 ² are active and 103 ³ are Phase 3, a high share that reflects large outcome programmes.
• 128 ⁴ started between January 2023 and September 2026: 90 ⁵ with a US site and 35 ⁶ with a China site.
• Oral PCSK9 inhibitors (enlicitide, AZD0780) appear in 45 ⁷ of the new studies and inclisiran in 32 ⁸.
• Lp(a)-lowering drugs appear in 14 ⁹ new studies, most of them large Phase 3 programmes.

Trial starts went from 6 ¹⁰ in 2020 to 28 ¹¹ in 2021, 22 ¹² in 2023 and a peak of 51 ¹³ in 2024, then 30 ¹⁴ in 2025. The pattern follows the launch of a few large programmes rather than a broad wave of new entrants: each Phase 3 programme registers several studies at once.

The United States hosts most studies, with 35 ¹⁵ of the 2024 starts. China's participation is small but rising, from 4 ¹⁶ studies in 2021 to 12 ¹⁷ in 2025. Chinese joint ventures, such as Arrowhead's partner Visirna, now run their own trials.

LDL cholesterol. Merck's oral PCSK9 inhibitor enlicitide and AstraZeneca's AZD0780 together appear in 45 ⁷ studies started since 2023. Novartis's twice-yearly siRNA inclisiran appears in 32 ⁸. NewAmsterdam's oral CETP inhibitor obicetrapib appears in 13 ²⁸.

Lp(a). Amgen's olpasiran, Lilly's lepodisiran and oral muvalaplin, Silence's zerlasiran and Novartis and Ionis's antisense pelacarsen together appear in 14 ⁹ new studies. These are few in number but each is a large outcome trial.

Triglycerides. APOC3 drugs, Ionis's olezarsen and Arrowhead's plozasiran, appear in 7 ²⁹ new studies, and ANGPTL3 drugs in 4 ³⁰.

Transthyretin. TTR silencers used in amyloid cardiomyopathy and polyneuropathy (vutrisiran, eplontersen, nucresiran) appear in 6 ³¹.

• Redemplo (plozasiran, APOC3 siRNA), approved 18 November 2025 (NDA 219947)
• Tryngolza (olezarsen, APOC3 antisense), 19 December 2024 (NDA 218614)
• Wainua (eplontersen, TTR), 21 December 2023 (NDA 217388)
• Amvuttra (vutrisiran, TTR), 13 June 2022 (NDA 215515)
• Leqvio (inclisiran, PCSK9), 22 December 2021 (NDA 214012)

The first APOC3 approvals are in familial chylomicronaemia syndrome, a rare disease. The larger prize is severe hypertriglyceridaemia and cardiovascular risk reduction, which needs further trials.

• This is a big-company game at the late stage. Almost all studies in this track are industry-sponsored, and 103 ³ are Phase 3. Cardiovascular outcome trials enrol very large numbers of patients and are beyond any start-up's budget.
• Early-stage opportunities are in delivery and new liver targets. Longer-acting siRNA, delivery to tissues beyond the liver and new targets such as AGT for hypertension are where small companies can create value, then partner.
• Watch Lp(a) outcome results. The first outcome trials were scheduled to read out from 2026. A positive result would open a very large market. A negative one would reset the whole class.
• One-time editing is the next step. Lilly's acquisition of Verve Therapeutics, completed in July 2025 (Lilly), shows that big pharma is also betting on one-time gene editing of PCSK9 and other lipid genes.

Every trial count is the totalCount of one ClinicalTrials.gov API v2 query, retrieved on 26 September 2026. Each numbered citation opens a record whose source link re-runs the query. The track includes interventional studies naming any of the listed siRNA, antisense or oral lipid drugs, from inclisiran to nucresiran. It is defined by drug rather than by disease, so it also covers transthyretin amyloidosis.

Counts are small and dominated by a few large programmes. Site-country counts overlap and China-only registrations are missing. Approval dates come from Drugs@FDA. Acquisitions and trial timelines are based on company announcements.