What Is Enpatoran?
Enpatoran is an investigational drug that is currently being studied in clinical trials. It is taken orally, typically in tablet form. Researchers are evaluating how Enpatoran works within the body and its potential to treat certain autoimmune conditions, particularly different forms of lupus. The development of Enpatoran is supported by sponsors such as EMD Serono Research & Development Institute, Inc. and Merck Healthcare KGaA, Darmstadt, Germany.
To date, clinical trials for Enpatoran have involved a total of 941 participants across 6 studies. These trials began in late 2021, with the most recent study projected to conclude in early 2026. The primary focus of these investigations is to assess the safety, tolerability, and effectiveness of Enpatoran in individuals with conditions such as Cutaneous Lupus Erythematosus and Systemic Lupus Erythematosus. Additionally, studies are being conducted in healthy volunteers and individuals with renal impairment to thoroughly understand how the drug is absorbed, distributed, metabolized, and excreted by the body.
Uses and Conditions Under Study
Enpatoran is currently under investigation for several medical conditions, with a significant focus on autoimmune diseases and the drug's interaction with the human body.
- Lupus Conditions: A substantial portion of the research on Enpatoran is dedicated to Cutaneous Lupus Erythematosus (CLE) and Systemic Lupus Erythematosus (SLE). Lupus is a chronic autoimmune disease where the immune system mistakenly targets and attacks healthy tissues, leading to widespread inflammation and potential damage to organs. CLE primarily manifests with skin-related symptoms, while SLE can affect various organ systems throughout the body. A total of 4 trials are exploring Enpatoran's potential to manage the symptoms and progression of these challenging lupus conditions.
- Healthy Volunteers: Two trials are being conducted in healthy participants. These studies are fundamental for establishing the foundational understanding of Enpatoran's pharmacokinetics (how the body absorbs, distributes, metabolizes, and excretes the drug) and pharmacodynamics (the drug's effects on the body). They also help to assess the drug's overall safety and tolerability in individuals who do not have the specific disease being targeted for treatment.
- Renal Impairment: One trial specifically investigates Enpatoran in individuals with renal impairment, or reduced kidney function. This type of study is critical for determining if dosage adjustments are necessary for patients whose kidneys may not process medications as efficiently, thereby ensuring the drug can be administered safely and effectively across different patient populations.
Dosing
Enpatoran is administered orally, primarily as tablets, including film-coated tablets. The dosing regimens observed in clinical trials vary depending on the study's purpose and the specific condition being investigated.
In several studies, participants received Enpatoran orally twice daily (BID). This regimen was often maintained for an extended period, such as from Day 1 to Day 168, which is approximately 24 weeks. Other trials involved a single oral dose of Enpatoran tablets, typically for pharmacokinetic studies to understand how the drug is processed by the body over a short period.
Researchers have explored different strengths of Enpatoran. Studies have included various dose levels, referred to as low dose, medium dose, and high dose. These different strengths are evaluated to determine the most effective and safest concentration for treating conditions like lupus. Additionally, specific cohorts have been established to study Enpatoran in individuals with normal renal function versus those with impaired renal function, which helps in understanding potential dosage adjustments needed for patients with kidney issues.
Side Effects
In a clinical trial involving 335 patients who received Enpatoran, certain side effects were reported more frequently compared to those who received a placebo. The most common side effect was upper respiratory tract infection, which occurred in 10.4% of patients taking Enpatoran, compared to 6.6% of patients on placebo.
Other common side effects that were more frequent with Enpatoran included:
- Nasopharyngitis (common cold): 4.8% on Enpatoran vs 1.7% on placebo
- Headache: 3.3% on Enpatoran vs 1.7% on placebo
- Asymptomatic bacteriuria (bacteria in urine without symptoms): 1.2% on Enpatoran vs 0.0% on placebo
Less common side effects reported in 0.6% of patients on Enpatoran (and 0.0% on placebo) included increased weight, increased alanine aminotransferase (a liver enzyme), increased aspartate aminotransferase (another liver enzyme), increased blood creatinine (a kidney function marker), and cough.
Some side effects were reported less frequently in patients taking Enpatoran compared to placebo:
- Urinary tract infection: 5.4% on Enpatoran vs 9.9% on placebo
- Diarrhea: 2.4% on Enpatoran vs 5.8% on placebo
- Influenza (flu): 1.5% on Enpatoran vs 5.0% on placebo
Clinical Trial Results
Results from the WILLOW study (NCT05162586) evaluated the effectiveness of Enpatoran in patients with Systemic Lupus Erythematosus (SLE) and Cutaneous Lupus Erythematosus (CLE).
Impact on Fatigue and Skin Symptoms
Patients treated with Enpatoran showed improvements in fatigue and skin-related symptoms. In Cohort A (Part 1, N=30 per arm), patients receiving Enpatoran 50 mg experienced an average improvement of 6.9 points in FACIT-Fatigue scores, compared to 3.0 points for those on placebo. For skin symptoms, patients on Enpatoran 50 mg saw an average reduction of 28.6 points in Skindex 29+3 Symptom Domain scores, while placebo patients had a reduction of 13.7 points. Lower scores indicate improvement.
In Cohort B (Part 1 + Part 2, N=90 per arm), patients taking Enpatoran 100 mg showed an average improvement of 5.1 points in FACIT-Fatigue scores, compared to 2.4 points for placebo. They also experienced an average reduction of 17.0 points in Skindex 29+3 Symptom Domain scores, compared to 9.2 points for placebo.
Corticosteroid Reduction
Enpatoran also helped some patients reduce their corticosteroid use. In Cohort A, 40% of patients (12 out of 30) on Enpatoran 50 mg achieved a clinically meaningful reduction in corticosteroids, compared to 20% (6 out of 30) on placebo. In the larger Cohort B (Part 1 + Part 2), 45.6% of patients (41 out of 90) on Enpatoran 100 mg achieved this reduction, compared to 40% (36 out of 90) on placebo.
Lupus Disease Activity
Measures of lupus disease activity also showed improvement. For cutaneous lupus, in Cohort A, 46.7% of patients (14 out of 30) on Enpatoran 100 mg achieved a Cutaneous Lupus Activity Investigator's Global Assessment (CLA-IGA) score of 0 or 1 (indicating clear or almost clear skin) at Week 24, compared to 23.3% (7 out of 30) on placebo.
For systemic lupus activity, in Cohort B (Part 1 + Part 2), 62.2% of patients (56 out of 90) on Enpatoran 100 mg achieved a British Isles Lupus Assessment Group (BILAG)-Based Composite Lupus Assessment (BICLA) response at Week 24, compared to 41.1% (37 out of 90) on placebo. Additionally, 85.6% of patients (77 out of 90) on Enpatoran 100 mg achieved a Systemic Lupus Erythematosus Responder Index-4 (SRI-4) response, compared to 55.6% (50 out of 90) on placebo.
Currently Recruiting Trials
Enpatoran is currently being investigated in clinical trials for individuals living with lupus, specifically focusing on its impact on cutaneous (skin-related) manifestations. These studies aim to understand how effective and safe Enpatoran is for patients.
One such study, titled "A Study of Enpatoran in Participants With Cutaneous Manifestations of Lupus With or Without Systemic Disease (ELOWEN-2)," is a global, multicenter, Phase 3 trial. This study (NCT07355218) is evaluating Enpatoran in participants with active cutaneous lupus erythematosus, whether or not they also have systemic disease. The trial is sponsored by EMD Serono Research & Development Institute, Inc. and plans to enroll approximately 202 participants. Treatment with Enpatoran will occur over 24 weeks, as part of a total study duration of up to 35 weeks.
Another ongoing Phase 3 study, "A Study of Enpatoran in Participants With Cutaneous Manifestations of Lupus With or Without Systemic Disease" (NCT07332481), shares a similar purpose. Also sponsored by EMD Serono Research & Development Institute, Inc., this trial is also designed to assess the efficacy and safety of Enpatoran over 24 weeks in individuals with active cutaneous manifestations of lupus erythematosus, with or without systemic involvement. This study also aims to enroll 202 participants, with a total study duration of up to 35 weeks.
Where to Participate
If you are interested in participating in a clinical trial for Enpatoran, there are currently 9 study sites across 8 cities in 6 states in the United States. These sites are actively seeking participants for the ongoing Phase 3 trials.
Current top locations include:
- Allen, Texas (2 sites)
- Upland, California
- DeBary, Florida
- Pembroke Pines, Florida
- Los Angeles, California
- Indianapolis, Indiana
- Troy, Michigan
- Atlanta, Georgia
To be eligible for these studies, participants must be between 18 and 75 years of age. The trials are open to all genders, but healthy volunteers and children are not eligible to participate.
Development Timeline
The journey of Enpatoran in clinical development began on November 5, 2021, with its first clinical trial. Since then, the development program has expanded significantly, with the latest trial projected to conclude on January 21, 2026. A total of 6 clinical trials have been conducted or are currently underway for Enpatoran, involving a combined enrollment of 941 participants.
Initial investigations into Enpatoran explored its potential for conditions such as Irritable Bowel Syndrome with Constipation (IBS-C) and hyperphosphatemia. As development progressed, the focus broadened, and Enpatoran entered studies for various forms of lupus, including Cutaneous Lupus Erythematosus and Systemic Lupus Erythematosus (SLE), as well as for renal impairment.
The development has progressed through different phases, including 3 Phase 1 studies, 1 Phase 2 study, and the current 2 Phase 3 studies. This progression reflects a growing understanding of Enpatoran's potential. The development of Enpatoran has been driven by EMD Serono Research & Development Institute, Inc. and Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany, with each sponsoring 3 trials.