Lepodisiran and Muvalaplin in 2026: Phase 3 Status and What Clinics Should Do Now

Lepodisiran and muvalaplin can produce large reductions in lipoprotein(a), or Lp(a), in phase 2 trials. Neither trial showed fewer heart attacks, strokes, cardiovascular deaths, or aortic-valve events. Those outcomes are being tested in large phase 3 programs that extend into 2029 and 2031.¹²³⁴

As of August 28, 2026:

• lepodisiran is investigational and its ACCLAIM-Lp(a) outcomes trial is active but no longer recruiting;
• muvalaplin is investigational and its MOVE-Lp(a) outcomes trial is recruiting;
• a longevity clinic should not advertise either drug as an available anti-aging treatment;
• the useful action today is to measure and interpret inherited cardiovascular risk correctly.

Review note, August 28, 2026: WLC replaced company press releases with the phase 2 papers and current trial records, added phase 3 status and completion dates, removed clinic promotion, and retained the boundary between biomarker lowering and clinical benefit.

Quick comparison

Question	Lepodisiran	Muvalaplin
Modality	Long-acting small interfering RNA injection	Once-daily oral small molecule
Phase 2 participants	320	233
Largest reported placebo-adjusted Lp(a) reduction	93.9 percentage points over days 60 to 180 at the pooled 400 mg dose	85.8% at 12 weeks with the intact Lp(a) assay at 240 mg/day
Current outcomes trial	ACCLAIM-Lp(a), NCT06292013	MOVE-Lp(a), NCT07157774
Trial status on August 28, 2026	Active, not recruiting	Recruiting
Estimated enrollment	17,300	10,450
Estimated primary completion	March 2029	March 2031
Cardiovascular-event benefit proven?	No	No

The percentages are not directly comparable because the trials used different drugs, schedules, populations, time windows, and assays.

Why Lp(a) is different from LDL-C

Lp(a) is an LDL-like particle with an additional apolipoprotein(a) component. Concentration is largely inherited and is associated with atherosclerotic cardiovascular disease and calcific aortic-valve stenosis.⁵

A standard lipid panel does not necessarily include Lp(a). LDL-C can look acceptable while Lp(a) remains elevated. That makes a one-time measurement useful for risk classification, especially when there is premature cardiovascular disease, a strong family history, familial hypercholesterolemia, aortic stenosis, or unexplained plaque.

The European Atherosclerosis Society consensus recommends measuring Lp(a) at least once in adulthood.⁵ It also emphasizes that clinicians should manage total cardiovascular risk while dedicated Lp(a)-lowering outcome data are pending.

Do not convert mg/dL to nmol/L with a single universal factor. Particle mass varies with apolipoprotein(a) isoform size. A clinic should report the assay and unit, then interpret the result within an established guideline and the patient’s overall risk.

What the lepodisiran phase 2 trial found

The ALPACA phase 2 trial randomly assigned 320 participants to placebo or several lepodisiran doses. Median baseline Lp(a) was 253.9 nmol/L.¹

For the primary endpoint, the placebo-adjusted time-averaged change from day 60 to day 180 was:

• 40.8 percentage points lower with 16 mg;
• 75.2 percentage points lower with 96 mg;
• 93.9 percentage points lower in the pooled 400 mg groups.

The reduction remained substantial across longer follow-up in the 400 mg groups. Serious adverse events occurred in 35 participants, but investigators did not attribute them to lepodisiran or placebo. Generally mild injection-site reactions were dose-dependent and occurred in up to 12% of participants in the highest-dose group.¹

This proves a large, durable biomarker effect. It does not prove fewer events.

Current phase 3 status

ACCLAIM-Lp(a), NCT06292013, is a randomized, double-blind, placebo-controlled phase 3 trial designed around major cardiovascular events. Its primary composite includes cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, and urgent coronary revascularization.²

The registry listed the trial as active but not recruiting on August 28, 2026, with estimated enrollment of 17,300 and estimated primary completion in March 2029.²

That is the trial that must answer the clinical question.

What the muvalaplin phase 2 trial found

The KRAKEN phase 2 trial randomized 233 participants with Lp(a) of at least 175 nmol/L and cardiovascular disease, diabetes, or familial hypercholesterolemia to placebo or oral muvalaplin for 12 weeks.³

Using an intact Lp(a) assay, the placebo-adjusted reductions were:

• 47.6% at 10 mg/day;
• 81.7% at 60 mg/day;
• 85.8% at 240 mg/day.

Using an apolipoprotein(a)-based assay, the reductions were smaller at the two higher doses. That assay difference is not a footnote to ignore. It shows why a clinic should not compare Lp(a) numbers without knowing the method.

The trial reported no safety or tolerability concern at the studied doses and concluded that cardiovascular-event effects require further investigation.³

Current phase 3 status

MOVE-Lp(a), NCT07157774, is the phase 3 cardiovascular-outcomes trial for muvalaplin. The registry listed it as recruiting, with estimated enrollment of 10,450 and primary completion in March 2031.⁴

An oral route may be operationally attractive if the drug eventually proves benefit and receives approval. That remains a future scenario, not a current clinic service.

Biomarker lowering is not the endpoint patients need

Lp(a) has stronger causal and epidemiologic support than many commercial biological-age markers. Even so, the decision threshold remains clinical outcomes.

The evidence ladder is:

1. Association: higher Lp(a) is associated with cardiovascular and valvular risk.
2. Genetics: inherited variation supports a causal role.
3. Drug effect: lepodisiran and muvalaplin lower the biomarker.
4. Clinical outcome: the drugs reduce cardiovascular events with acceptable harms.
5. Implementation: approved use identifies who benefits, at what dose, and with what monitoring.

The programs are between steps three and four. A clinic that markets step five today is skipping the evidence.

What a serious clinic should do now

A credible preventive workflow should include:

1. Measure Lp(a) at least once. Record the assay and unit.
2. Measure the rest of atherogenic burden. ApoB, LDL-C, non-HDL-C, triglycerides, blood pressure, smoking, glycemic status, and kidney function still matter.
3. Document family history. Include premature myocardial infarction, stroke, sudden death, familial hypercholesterolemia, and aortic stenosis.
4. Assess existing disease and symptoms. High Lp(a) in someone with established cardiovascular disease is not the same scenario as an isolated result in a healthy adult.
5. Use imaging selectively. Coronary calcium or other imaging should answer a risk question, not serve as an automatic upsell.
6. Refer when appropriate. Complex lipid patterns, early plaque, symptoms, or very high inherited risk warrant preventive-cardiology or lipid-specialist input.
7. Optimize proven risk factors. The absence of a dedicated approved Lp(a) drug does not justify neglecting LDL/ApoB lowering, blood pressure, smoking cessation, diabetes prevention, exercise, or sleep-apnea treatment.
8. Discuss trials accurately. Trial enrollment is not commercial access, and a registry listing is not approval.

For a wider test context, use the longevity-clinic blood-panel guide.

Claims patients should reject

Reject these statements unless the clinic can provide current regulatory and trial evidence:

• “The new Lp(a) shot is available as a longevity treatment.”
• “Lowering Lp(a) has already been proven to prevent heart attacks.”
• “A supplement stack can normalize genetically elevated Lp(a).”
• “Normal LDL-C means high Lp(a) can be ignored.”
• “A single conversion factor makes mg/dL and nmol/L interchangeable.”
• “Everyone with a high result needs advanced imaging or an experimental drug.”

The appropriate next step depends on overall risk, not on the biomarker alone.

Questions to ask a clinic

1. Is Lp(a) included in the baseline assessment?
2. Which assay and unit do you use?
3. How do you interpret Lp(a) alongside ApoB and LDL-C?
4. What family-history fields do you collect?
5. Which finding triggers a preventive-cardiology referral?
6. When would imaging change management?
7. What evidence-based risk factors will you treat now?
8. How do you distinguish approved treatment, off-label care, and a research trial?
9. Will you coordinate the plan with my existing physician?
10. How will you update the plan when phase 3 outcomes become available?

Bottom line

Lepodisiran and muvalaplin are credible Lp(a)-lowering research programs, not proven longevity treatments. Their phase 2 trials show large biomarker effects. Their phase 3 trials must establish whether those effects reduce cardiovascular events.

The best clinic response in 2026 is not to sell access. It is to stop missing inherited cardiovascular risk, interpret it with the rest of the patient’s risk profile, and use established prevention while outcomes trials continue.

Footnotes

1. Nissen SE, et al. Lepodisiran, A Long-Duration Small Interfering RNA Targeting Lipoprotein(a). New England Journal of Medicine. 2025. ↩ ↩² ↩³

2. ACCLAIM-Lp(a), NCT06292013, ClinicalTrials.gov, status reviewed August 28, 2026. ↩ ↩² ↩³

3. Nicholls SJ, et al. Oral Muvalaplin for Lowering of Lipoprotein(a): A Randomized Clinical Trial. JAMA. 2025. ↩ ↩² ↩³

4. MOVE-Lp(a), NCT07157774, ClinicalTrials.gov, status reviewed August 28, 2026. ↩ ↩²

5. Kronenberg F, et al. Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement. European Heart Journal. 2022. ↩ ↩²