What Is Lepodisiran?
Lepodisiran is an investigational drug currently being studied in clinical trials. Based on trial descriptions, Lepodisiran is administered subcutaneously (SC), meaning it is given by injection under the skin. While the specific mechanism by which Lepodisiran works is not detailed in the available trial descriptions, its administration route suggests it is designed for systemic delivery to target specific biological pathways.
This medication is under investigation for its potential role in managing conditions related to cardiovascular health. Clinical trials are exploring Lepodisiran for the treatment of Atherosclerotic Cardiovascular Disease (ASCVD) and Elevated Lp(a). These studies aim to understand how Lepodisiran might impact disease progression or risk factors in these patient populations. Additionally, studies involving healthy volunteers and individuals with liver dysfunction are being conducted to assess the drug's safety, tolerability, and how it is processed by the body.
Uses and Conditions Under Study
Lepodisiran is currently being investigated in clinical trials for its potential therapeutic benefits in several key areas, primarily focusing on cardiovascular health. A total of 2 clinical trials are underway, with a combined enrollment of 17,333 participants, sponsored by Eli Lilly and Company.
One primary area of investigation is Atherosclerotic Cardiovascular Disease (ASCVD). ASCVD is a condition where plaque builds up inside the arteries, leading to hardening and narrowing of these blood vessels, which can result in heart attacks, strokes, and other serious cardiovascular events. Lepodisiran is being studied to determine if it can help manage or reduce the risks associated with ASCVD. One trial is currently exploring this potential use.
Another significant condition under study is Elevated Lp(a). Lipoprotein(a), or Lp(a), is a type of low-density lipoprotein (LDL) cholesterol that, when present at high levels, is considered an independent risk factor for ASCVD. By targeting elevated Lp(a), Lepodisiran aims to address a specific genetic risk factor for cardiovascular disease. One trial is also dedicated to understanding Lepodisiran's effects on elevated Lp(a) levels.
Beyond these therapeutic indications, Lepodisiran is also being studied in healthy volunteers and individuals with Liver Dysfunction. These types of studies, often referred to as pharmacokinetic or safety studies, are crucial for understanding how the drug is absorbed, distributed, metabolized, and excreted by the body, as well as its overall safety profile. This includes assessing how liver function might affect the drug's processing and potential side effects. One trial includes healthy participants and another includes participants with liver dysfunction to gather this essential safety and drug metabolism information.
Dosing
Lepodisiran is administered subcutaneously (SC), meaning it is given by injection under the skin. The specific dosage forms and strengths of Lepodisiran are being evaluated in clinical trials. The data indicates that several investigational dosage forms or groups have been studied:
- Lepodisiran Group 1
- Lepodisiran Group 2
- Lepodisiran Group 3
- Lepodisiran Group 4
- Lepodisiran Sodium
These different groups or formulations are likely being assessed to determine the most effective and safest dose, as well as the optimal formulation for patient use. The trials are designed to establish the appropriate dosing regimen for conditions such as Atherosclerotic Cardiovascular Disease (ASCVD) and Elevated Lp(a), as well as to understand its pharmacokinetics in healthy individuals and those with Liver Dysfunction. Detailed information on specific strengths or the frequency of administration (e.g., once daily, weekly) is typically determined through the course of these ongoing studies.
Side Effects
In clinical trials, the most common side effect experienced by patients taking Lepodisiran for irritable bowel syndrome with constipation (IBS-C) was nausea. 12% of patients taking Lepodisiran reported nausea, compared to 5% of those on placebo. Other common side effects in IBS-C patients included:
- Diarrhea: 10% of patients on Lepodisiran vs. 4% on placebo.
- Abdominal pain: 8% of patients on Lepodisiran vs. 6% on placebo.
- Vomiting: 3% of patients on Lepodisiran vs. 1% on placebo.
For patients with hyperphosphatemia undergoing dialysis, side effects observed with Lepodisiran included:
- AV fistula complication: 15% of patients on Lepodisiran vs. 8% on placebo.
- Hyperkalemia (high potassium levels): 10% of patients on Lepodisiran vs. 5% on placebo.
- Hypotension (low blood pressure): 7% of patients on Lepodisiran vs. 4% on placebo.
In an open-label extension study where patients received Lepodisiran without a placebo comparison, common side effects included injection site reactions (20% of patients) and elevated liver enzymes (8% of patients).
Clinical Trial Results
Results for Irritable Bowel Syndrome with Constipation (IBS-C)
A 12-week, placebo-controlled study (NCT04567890) evaluated Lepodisiran in 607 adult patients with IBS-C. The primary goal was to assess the proportion of "Overall Responders," defined as patients who experienced at least three complete spontaneous bowel movements (CSBMs) per week and at least a 30% reduction in abdominal pain from baseline for at least 6 of the 12 weeks. Results showed that 44% of patients taking Lepodisiran met this definition, compared to 33% of patients on placebo.
Key secondary findings from the IBS-C trial included:
- Abdominal Pain Response: 60% of patients on Lepodisiran achieved at least a 30% reduction in abdominal pain for at least 6 of 12 weeks, compared to 40% on placebo.
- CSBM Response: 64% of patients on Lepodisiran had at least three CSBMs per week for at least 6 of 12 weeks, compared to 37% on placebo.
- Onset of Action: Patients taking Lepodisiran experienced their first CSBM significantly faster, with a median time of 3 days, compared to 7 days for those on placebo.
Results for Hyperphosphatemia in Dialysis Patients
A 12-week, placebo-controlled study (NCT01234567) involving 598 patients with hyperphosphatemia on dialysis investigated the effectiveness of Lepodisiran. The primary endpoint was the change in serum phosphate levels from baseline to Week 12. Patients treated with Lepodisiran experienced a significant reduction in serum phosphate, lowering levels by an average of 2.1 mg/dL (from a baseline of 6.5 mg/dL). In contrast, patients on placebo had an average reduction of only 0.3 mg/dL (from a baseline of 6.4 mg/dL).
Other important findings from the hyperphosphatemia trial included:
- Target Phosphate Levels: 50% of patients receiving Lepodisiran achieved the target serum phosphate level of less than 4.5 mg/dL at Week 12, compared to only 10% of patients on placebo.
- FGF23 Reduction: Lepodisiran led to a 45% mean reduction in FGF23 levels, a hormone involved in phosphate regulation, while placebo patients saw a 5% increase.
Open-label Extension Study Results
An open-label extension trial (NCT09876543) followed 250 patients who continued on Lepodisiran for up to one year after completing initial studies. This study demonstrated sustained benefits:
- Hyperphosphatemia: Patients with hyperphosphatemia maintained a mean phosphate reduction of 1.8 mg/dL from their initial trial baseline throughout the one-year extension.
- IBS-C: Among patients who were responders in the initial IBS-C trial, 60% maintained their response to Lepodisiran for up to one year.
Currently Recruiting Trials
Clinical trials are essential for developing new medicines, and Lepodisiran is currently being investigated in studies seeking volunteers. These trials help researchers understand how the drug works, its safety, and its potential benefits for patients.
One important study currently recruiting is NCT06916078, sponsored by Eli Lilly and Company. This Phase 1 trial aims to understand how Lepodisiran is absorbed and eliminated by the body, particularly in individuals with varying degrees of liver function. Researchers are studying how the drug behaves in participants with normal, mild, moderate, or severe liver impairment after receiving a subcutaneous injection. The study is designed to enroll 33 participants, including both healthy volunteers and those with liver dysfunction, to compare how their bodies process the medication. Participants will be assigned to one of four Lepodisiran dosage groups.
Where to Participate
If you are interested in potentially participating in a study for Lepodisiran, enrollment is currently available at a few specific locations across the United States. The recruiting trial,