What Is Efinopegdutide?
Efinopegdutide is an investigational medication currently being studied in clinical trials. It is administered as a subcutaneous injection, meaning it is injected under the skin. The specific mechanism by which Efinopegdutide works is not detailed in the provided trial descriptions.
Clinical research is exploring Efinopegdutide as a potential treatment for various liver conditions, including different forms of fatty liver disease and liver impairment. To date, seven clinical trials have been conducted or are underway, involving a total of 856 participants. These trials aim to evaluate the drug's safety and effectiveness for its intended uses.
Uses and Conditions Under Study
Efinopegdutide is primarily being investigated for its potential to treat conditions related to fatty liver disease. This includes Nonalcoholic Fatty Liver Disease (NAFLD), Nonalcoholic Steatohepatitis (NASH), and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). These conditions involve the accumulation of excess fat in the liver, which can lead to inflammation and liver damage. Efinopegdutide is being studied to see if it can help manage or improve these liver conditions. These related conditions are collectively being explored in 14 mentions across the clinical trials.
Additionally, Efinopegdutide is being studied in healthy volunteers and participants with hepatic impairment (impaired liver function). These studies, mentioned in four trials, typically assess how the drug is processed by the body (pharmacokinetics) and its safety profile in different populations. This helps researchers understand how the drug might behave in individuals with varying degrees of liver health.
Dosing
Efinopegdutide is administered as a subcutaneous injection, typically using a single-use prefilled syringe. The drug has been studied in various dose-escalation regimens and frequencies.
Investigational strengths include 2 mg, 4 mg, 7 mg, 10 mg, and 15 mg. The frequency of administration has varied, with some studies exploring doses given once per week (Q1W) and others every two weeks (Q2W). For example, specific regimens under investigation include Efinopegdutide Q1W 10 mg, Efinopegdutide Q2W 10 mg, and Efinopegdutide Q2W 15 mg. The drug has also been studied in participants with moderate and severe hepatic impairment, as well as in healthy control groups, to understand its effects across different patient populations.
Side Effects
In a study (NCT04944992) involving participants with Nonalcoholic Fatty Liver Disease (NAFLD), 88.9% of those taking Efinopegdutide experienced an adverse event, compared to 72.6% of participants taking semaglutide. Discontinuation from the study due to an adverse event occurred in 5.6% of participants receiving Efinopegdutide, while no participants (0%) discontinued due to an adverse event in the semaglutide group.
A separate study (NCT06052566) evaluating Efinopegdutide in participants with hepatic impairment found that adverse events were reported by 4 participants in the healthy-matched control group, 3 participants with moderate hepatic impairment, and 4 participants with severe hepatic impairment. No participants in this study discontinued the intervention due to an adverse event across any of the groups.
Clinical Trial Results
Nonalcoholic Fatty Liver Disease (NAFLD)
A study (NCT04944992) investigated Efinopegdutide in participants with Nonalcoholic Fatty Liver Disease over 24 weeks, comparing it to semaglutide. Key findings included:
- Participants treated with Efinopegdutide experienced an average absolute reduction of 14.9 percentage points in liver fat content, as measured by MRI-PDFF. In comparison, participants receiving semaglutide had an average absolute reduction of 8.8 percentage points.
- The relative reduction in liver fat content was 72.7% for those on Efinopegdutide, versus 42.3% for those on semaglutide.
- Body weight decreased by an average of 8.5% in the Efinopegdutide group, compared to a 7.1% decrease in the semaglutide group.
- Efinopegdutide led to significant improvements in several cholesterol and triglyceride levels:
- Apolipoprotein B (apoB) decreased by 14.7%, compared to a 9.2% decrease with semaglutide.
- Low-density lipoprotein cholesterol (LDL-C) decreased by 13.0%, compared to a 6.9% decrease with semaglutide.
- Non-high-density lipoprotein cholesterol (Non-HDL-C) decreased by 16.8%, compared to an 11.0% decrease with semaglutide.
- Total cholesterol decreased by 15.2%, compared to an 8.0% decrease with semaglutide.
- Triglycerides (TG) decreased by 30.9%, compared to a 23.3% decrease with semaglutide.
- High-density lipoprotein cholesterol (HDL-C) decreased by 8.1% with Efinopegdutide, while it increased by 3.6% with semaglutide.
Hepatic Impairment
A study (NCT06052566) examined how Efinopegdutide is processed in the body of individuals with varying degrees of liver function. This pharmacokinetic study included healthy participants and those with moderate or severe hepatic impairment.
- The overall exposure to Efinopegdutide, measured by the area under the curve (AUC0-inf), was similar across groups: 146 hr*µg/mL in healthy controls, 143 hr*µg/mL in moderate impairment, and 152 hr*µg/mL in severe impairment.
- The apparent terminal half-life of Efinopegdutide was approximately 115 hours in healthy individuals, extending to 146 hours in those with moderate hepatic impairment and 149 hours in those with severe hepatic impairment.
- Maximum plasma concentration (Cmax) was 0.474 µg/mL in healthy controls, 0.348 µg/mL in moderate impairment, and 0.404 µg/mL in severe impairment.
These results suggest that while the drug may stay in the body slightly longer in individuals with liver impairment, the overall amount of drug exposure remains largely consistent, indicating that liver impairment may not significantly alter how Efinopegdutide is processed.
Currently Recruiting Trials
Clinical trials are a vital step in bringing new medicines like Efinopegdutide to patients. These studies carefully evaluate a drug's safety and how well it works for specific conditions. As of now, there are no clinical trials for Efinopegdutide actively recruiting new participants. This means that at this time, no studies are accepting new volunteers to test this investigational treatment.
When Efinopegdutide trials do open for recruitment, they will seek participants who meet very specific health criteria. Typically, these studies are designed for individuals with particular medical conditions, rather than healthy volunteers. Children are generally not included in Efinopegdutide research. The eligibility criteria for any future trial would specify the exact age range, gender (which has historically been open to all), and health status required. For example, a trial might focus on adults living with a specific liver condition or metabolic disorder, aiming to understand how Efinopegdutide impacts their health outcomes. Each trial would clearly outline what is being studied, such as the drug's dosage, its effects on disease progression, or its safety profile. Participants would also be informed about the trial's phase, which indicates how far along the drug is in its development journey, and the target number of volunteers needed to gather sufficient data. While no opportunities are available right now, those interested in future research for Efinopegdutide should monitor official clinical trial registries for updates on new studies.
Where to Participate
Currently, there are no active clinical trial sites for Efinopegdutide accepting new participants. This means that no specific locations, cities, or states are presently conducting recruiting studies for this investigational drug.
When Efinopegdutide trials are recruiting, they typically seek a broad range of adult participants. While the specific age range is not always specified, trials generally include adults of all genders. It is important to note that these studies are not designed for healthy volunteers; instead, they focus on individuals with particular medical conditions relevant to Efinopegdutide's potential therapeutic uses. Children are also not eligible to participate in Efinopegdutide clinical trials. Future trial locations, when available, would be listed on official registries, providing details on where interested and eligible individuals could potentially enroll.
Development Timeline
The journey of Efinopegdutide began on June 30, 2021, when the first clinical trial was initiated. Since then, the development program has steadily advanced, with the latest trial projected to conclude by February 20, 2025. This research has been driven entirely by Merck Sharp & Dohme LLC, which has sponsored all seven clinical trials for Efinopegdutide.
Initially, Efinopegdutide's potential was explored for conditions such as Irritable Bowel Syndrome with Constipation (IBS-C) and hyperphosphatemia. As research progressed, the scope of investigation significantly expanded, reflecting a growing understanding of the drug's potential applications. The development pipeline broadened to include a range of liver and metabolic conditions, such as Nonalcoholic Steatohepatitis (NASH), Nonalcoholic Fatty Liver Disease (NAFLD), Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), also known as Fatty Liver, Nonalcoholic, Hepatic Impairment, Liver Disease, and Metabolic Dysfunction-associated Steatohepatitis (MASH).
Across these investigations, Efinopegdutide has progressed through early and mid-stage clinical development. The program includes three Phase 1 trials, which primarily assess safety and dosage, and four Phase 2 trials, designed to evaluate effectiveness and further safety in a larger group of patients. To date, these seven trials have collectively enrolled approximately 856 participants, contributing valuable data to understand Efinopegdutide's profile and its potential role in treating various complex conditions.