Lilly Advances Muvalaplin into Phase III in China: First Oral Lp(a)-Lowering Therapy Targeting MACE Risk
Lilly initiates Phase III trial of Muvalaplin in China and globally to reduce MACE in adults with elevated Lp(a), marking the first oral therapy in this class.
Eli Lilly and Company, along with Lilly Suzhou Pharmaceutical Co., Ltd. and Lilly del Caribe, Inc., has initiated a Phase III randomized, double-blind, placebo-controlled global study of Muvalaplin (LY3473329) in patients with elevated lipoprotein(a) [Lp(a)] and increased risk of atherosclerotic cardiovascular disease (ASCVD).
The trial, titled MOVE-Lp(a), will evaluate whether once-daily oral Muvalaplin can reduce the incidence of major adverse cardiovascular events (MACE). In China, the study will recruit approximately 650 participants, while globally the target enrollment is 10,450 patients.
Trial Design and Objectives
- Study type: Phase III, randomized, double-blind, placebo-controlled, parallel-group, international multicenter trial.
- Population: Adults ≥18 years with Lp(a) ≥175 nmol/L and either:
- a history of ASCVD (coronary artery disease, ischemic stroke, peripheral artery disease), or
- increased risk for a first ASCVD event.
- Exclusion criteria: Recent major cardiovascular event (<90 days), uncontrolled hypertension, advanced heart failure, severe renal impairment, or active malignancy.
- Intervention: Muvalaplin 120 mg tablet, orally, once daily.
- Control: Placebo tablet, orally, once daily.
Primary Endpoint:
- Time to first occurrence of MACE-4 (cardiovascular death, myocardial infarction, ischemic stroke, or urgent coronary revascularization).
Secondary Endpoints:
- Percent change in Lp(a) from baseline at Week 4.
- Time to MACE-3, modified MACE-3, coronary MACE-3, and MACE-3 + major adverse limb events (MALE).
Scientific Rationale: Targeting Lp(a)
Lp(a) elevation is an established independent risk factor for ASCVD, yet no approved therapies specifically lower Lp(a). Muvalaplin, an oral small-molecule Lp(a)-lowering agent, disrupts Apo(a)–ApoB interactions to prevent the formation of Lp(a) particles, without affecting Apo(a) expression.
Phase II data (NCT05563246) demonstrated:
- 47–86% reductions in Lp(a) depending on dose.
- Significant improvements in ApoB levels.
- Up to 96% of patients achieving Lp(a) <125 nmol/L at higher doses.
This trial represents the first late-stage global study of an oral Lp(a)-lowering therapy, offering a convenient alternative to injectables.
Global Competitive Landscape and HRS-5346/Merck Deal
While Muvalaplin is the first oral small-molecule Lp(a)-lowering therapy in Phase III, the competitive landscape is advancing:
- HRS-5346 (Jiangsu Hengrui / Merck outside China) is currently in Phase II.
- AZD4954 (AstraZeneca) and JX2201 (Jingxin Pharma) are in Phase I.
- YSJ202018 (Shenyang Sunshine Pharma) remains in preclinical development.
Notably, in March 2025, Hengrui licensed HRS-5346 to Merck for global development and commercialization outside Greater China. Terms included a $200M upfront payment and potential milestone payments up to $1.77B, plus royalties on net sales. This deal highlights the high commercial and scientific interest in Lp(a)-targeted therapies and underscores the fast-moving nature of this market.
Pipeline Comparison: Lp(a)-Lowering Small Molecules
| Drug Ingredient | Developer | Global Dev. Status | China Dev. Status | MOA / Target | Drug Type | Global Indication Status |
|---|---|---|---|---|---|---|
| Muvalaplin (LY3473329) | Eli Lilly | Phase III (2025-09-01) | Phase III (2025-09-01) | Lp(a)-lowering small molecule (blocks Apo(a)-ApoB assembly) | Oral small molecule | ASCVD, hyperlipidemia |
| HRS-5346 | Jiangsu Hengrui / Merck | Phase II (2025-02-06) | Phase II (2025-02-06) | Lp(a)-lowering small molecule | Oral chemical drug | Hyperlipoproteinemia(a) |
| AZD4954 | AstraZeneca | Phase I (2025-05-20) | Phase I (2025-05-20) | Lp(a)-lowering small molecule | Oral chemical drug | Hyperlipoproteinemia(a) |
| JX2201 | Jingxin Pharma | Phase I (2025-03-18) | Phase I (2025-03-18) | Lp(a)-lowering small molecule | Oral chemical drug | Hyperlipoproteinemia(a) |
| YSJ202018 | Shenyang Sunshine Pharma | Preclinical | Preclinical | Lp(a)-lowering small molecule (AI-designed) | Chemical drug / AI tech | Cardiovascular diseases |
Outlook
If successful, Muvalaplin could become the first approved oral therapy for Lp(a)-driven ASCVD, offering a convenient alternative to injections and potentially reshaping cardiovascular prevention.
The global Lp(a) pipeline remains limited, but licensing deals such as Hengrui–Merck for HRS-5346 demonstrate significant multinational investment and validation of this target. Lilly’s Phase III leadership in this space positions it strongly for a first-mover advantage.
Major academic centers participating in China include Fudan University Zhongshan Hospital and Peking University First Hospital, underscoring the country’s growing integration into global cardiovascular drug development.
References
- ClinicalTrials.gov NCT05563246 – Muvalaplin Phase II study.
- Clinical Trial Registry of China (CTR20253466).
- Hengrui–Merck HRS-5346 licensing deal, March 2025 press releases.