Sub-Q = subcutaneous; ASO = antisense oligonucleotide; CVRR = cardiovascular risk reduction; ASCVD = atherosclerotic cardiovascular disease; siRNA = small interfering RNA; LNP = lipid nanoparticle; IV = intravenous; P1/P2/P2b/P3 = Phase 1/2/2b/3.

Pipeline Deep Dive

Below is a deep dive of global Lp(a) targeting assets furthest along in clinical and preclinical development:

1. Pelacarsen (Novartis)

Trial Progress / Other Milestones

• Novartis has initiated an open-label extension study (NCT07517263) for continued data collection.^[7]
• The trial has not had any interim or final readouts, as Novartis projects the first readout to appear in H2 2026.^[8] Since the readout is event-driven (likely cardiac events / failures), the readout timing may shift.
• Novartis is targeting an FDA submission in 2026.^[8]
• The most recent clinical data for pelacarsen comes from its phase 2 trial readout in 2020, where all doses of the therapy induced Lp(a) lowering, with an 80% reduction in Lp(a) in the highest dose cohort compared to 6% in the placebo control.^[9][10]

2. Olpasiran (Amgen)

Trial Progress / Other Milestones

• Amgen has additional phase 3 trials pursuing a subsequent, broader indication in primary prevention of ASCVD (NCT07136012) as well as a coronary artery plaque focused ASCVD study (NCT07293260).^[12][13][14]
• The most recent clinical trial results come from olpasiran's phase 2 trial, where the therapy had a dose-dependent range of 70.5% to 101.1% placebo-adjusted mean change in Lp(a) levels from baseline.^[15]

3. Lepodisiran (Eli Lilly)

Trial Progress / Other Milestones

• In addition to ACCLAIM-Lp(a), Lilly has more recently kicked off another phase 3 trial, ACCLAIM-CTA, focused on patients with coronary artery disease (NCT07613294).^[19]
• A recently completed phase 1 trial (NCT06916078) in patients with hepatic impairment (i.e., reduced liver function) indicates future plans for indication expansion beyond heart disease.^[20]
• Lepodisiran's most recent clinical data was generated from its phase 2 ALPACA trial in 2025, where a 94% reduction in Lp(a) levels was achieved at the highest tested dose.^[21]

4. Muvalaplin (Eli Lilly)

Trial Progress / Other Milestones

• Phase 3 trial results have not yet read out, as completion is estimated for 2031.
• The most recent clinical data is from the phase 2 KRAKEN trial (NCT05563246), where muvalaplin achieved up to 86% placebo-adjusted reductions in Lp(a) levels.^[23][24]

5. Zerlasiran (Silence Therapeutics)

Trial Progress / Other Milestones

• Phase 2 trial results showed a mean time-averaged percent reduction in Lp(a) against placebo ranging from 81% to 86% based on dosage cohort.^[27]
• Silence Therapeutics indicates that zerlasiran is ready for a phase 3 trial, but the company is seeking a partner to help fund the study.^[28]
• Silence Therapeutics further claims that additional data is anticipated in 2026, although it is unclear what trial that data would be generated from.^[28]

6. CTX320 and CTX321 (CRISPR Therapeutics)

Trial Progress / Other Milestones

• CTX320 single dose administration demonstrated a 95% reduction in plasma Lp(a), which was sustained for the year-long trial duration.^[29]
• Note: CRISPR Therapeutics' pipeline does not list CTX320 but does list CTX321, which is the next-generation version of its gene therapy targeting the Lp(a) gene, with twice as high editing efficiency compared to CTX320.^[31][32] It is likely the case that CTX320 will not have any further investments made or trials conducted, as the company focuses on pushing CTX321 into the clinic. CTX321 is currently in IND-enabling studies and further updates are expected in 2026.

7. KYLO-11 (Hygieia Pharma)

Trial Progress / Other Milestones

• The phase 2 trial has only recently started, and includes sites in both China and the US in pursuit of global market entry.
• Secondary endpoint results from the China-based phase 1 trial demonstrated a median reduction of serum Lp(a) ranging from 53% to 97%, with a sustained response for 48 weeks.^[35]
• KYLO-11 is one of Hygieia Pharma's furthest-developed clinical stage assets and likely a big focus area for resources and investment in the coming few years.^[36]

8. DII235 (Novartis)

Trial Progress / Other Milestones

• Argo announced first patient dosing in the phase 2b trial at the start of 2026.^[40] Data readouts are still pending, as the study's primary completion is estimated for Q2 of 2027.^[39]

9. VERVE-301 (Verve Therapeutics / Eli Lilly)

Trial Progress / Other Milestones

• No recent updates have been provided on the development of VERVE-301. The most recent announcement came in May 2025, when the asset was in active preclinical studies.^[44]

10. MK-7262 (Merck)

Trial Progress / Other Milestones

• No readout results have been published from the ongoing phase 2 trial, as it kicked off in September 2026.^[45] The trial is set exclusively in China, meaning additional phase 2/3 trials will be needed for US and global market entry.

Additional Therapies in the Pipeline

There are additional assets in the preclinical / IND phase of development also pursuing Lp(a) targeted CVD indications:

1. YS2302018 (AstraZeneca)

Originally developed by CSPC, global rights to this small molecule Lp(a) disruptor were sold to AstraZeneca (AZ) in 2024.^[48] The therapy was in preclinical stages, and there have not been any updates from AZ since then. AZ's 2025 annual report mentioned the acquisition with no further updates on trial progress.^[49] The therapy is also not listed on AZ's pipeline and does not yet have a publicly disclosed AZ drug development code.^[50]

2. STX-1200 (Scribe Therapeutics)

Scribe's CRISPR-based gene editing therapy is in the IND-enabling stage, with Scribe actively pushing the therapy towards the clinic. In H2 2025, Scribe outlined preclinical data demonstrating greater than 95% Lp(a) lowering at low doses, highlighting its differentiating low-dose potency versus other Lp(a) targeting gene therapies.^[51] Just recently, in September 2026, Scribe announced additional funding for the therapy and hopes of getting it into a phase 1 trial by 2027.^[52]

Concluding Remarks

Lp(a) is an exciting target for drug developers for two key reasons:

• Approximately 20% of the global adult population has elevated Lp(a) levels, making for an expansive total addressable market.^[53]
• Lp(a) levels appear to be genetically determined and cannot be modulated with lifestyle factors, resulting in a much greater need for pharmacotherapeutic treatment options to address elevated Lp(a).

With the current landscape, Eli Lilly has the strongest portfolio of Lp(a) targeting drugs, with lepodisiran and muvalaplin both in phase 3 trials, as well as an additional preclinical stage bet through its acquisition of Verve Therapeutics. Most importantly, all three assets have different mechanisms of action, providing diversity and combinatory potential for the therapies both amongst each other and with other CVD focused assets in Lilly's pipeline.

Over the last few decades, statins / LDL-lowering drugs became a permanent pillar of modern heart disease management and treatment. One of these therapies may kick off a new class of Lp(a) lowering drugs that serves as the next pillar in heart disease for decades to come.