Efruxifermin Clinical Trials

What Is Efruxifermin?

Efruxifermin is an investigational medication currently being studied in clinical trials. It is administered by subcutaneous injection, meaning it is injected under the skin. This drug is being investigated for the treatment of various chronic liver conditions, including Nonalcoholic Steatohepatitis (NASH) and Metabolic Dysfunction-Associated Steatohepatitis (MASH). These conditions are characterized by fat accumulation in the liver, which can lead to inflammation and liver damage.

As of the latest data, Efruxifermin is being evaluated across 4 clinical trials with a total enrollment of 4,628 participants. The first trial began on February 23, 2021, and the latest trial started on July 30, 2024. These studies are sponsored by Akero Therapeutics, Inc., an industry sponsor, to assess the drug's safety and effectiveness.

Uses and Conditions Under Study

Efruxifermin is being investigated for a range of chronic liver diseases primarily related to fat accumulation and inflammation. These conditions collectively affect millions of people worldwide and can progress to more severe liver damage, including fibrosis and cirrhosis.

The main conditions under study include:

• Nonalcoholic Steatohepatitis (NASH) and Metabolic Dysfunction-Associated Steatohepatitis (MASH): These are chronic liver diseases characterized by fat in the liver, inflammation, and liver cell damage. Efruxifermin is being studied to see if it can improve these markers of liver health. These conditions are mentioned across 2 trials specifically for NASH, 1 trial for MASH, and 1 trial for NASH/MASH.
• MASH With Fibrosis and NASH With Fibrosis: These conditions represent a more advanced stage of liver disease where, in addition to fat and inflammation, there is also scarring (fibrosis) in the liver. Efruxifermin is being investigated for its potential to reduce or prevent the progression of this fibrosis. Each of these specific conditions is being studied in 1 trial.
• Nonalcoholic Fatty Liver Disease (NAFLD) / Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): These terms refer to the presence of excess fat in the liver not caused by heavy alcohol use. While often less severe than NASH or MASH, they can progress. Efruxifermin is being studied in 1 trial that includes NAFLD/MASLD.

In total, Efruxifermin is being investigated across 4 clinical trials for these various forms of liver disease, aiming to address the underlying causes and progression of metabolic liver dysfunction.

Dosing

Efruxifermin is administered as a solution by subcutaneous (SC) injection. This means the medication is injected under the skin, typically by a healthcare professional or, if instructed, by the patient themselves.

In clinical trials, different strengths of Efruxifermin have been studied to determine the most effective and safe dose for patients with liver conditions. The dosage forms studied include:

• Efruxifermin 28 mg: This strength has been investigated in clinical trials.
• Efruxifermin 50 mg: This strength has also been studied, including in an open-label rollover study, which typically involves participants from previous trials continuing treatment.

These specific strengths, 28 mg and 50 mg, are being evaluated for their efficacy and safety in treating conditions such as NASH, MASH, and related liver diseases. The frequency and duration of these injections are determined by the specific study protocol for each clinical trial.

Side Effects

In a clinical trial involving patients taking Efruxifermin, the most commonly reported side effect was diarrhea. 50.6% of patients on Efruxifermin experienced diarrhea, compared to 30.2% of those on placebo. Nausea was also common, affecting 42.2% of patients taking Efruxifermin, versus 30.2% on placebo.

Other common side effects reported in the trial included:

• Increased appetite: 21.7% of patients on Efruxifermin experienced this, compared to 7.0% on placebo.
• Injection-site erythema (redness): 21.7% of patients on Efruxifermin experienced this, compared to 18.6% on placebo.
• Vomiting: 19.3% of patients on Efruxifermin experienced this, compared to 16.3% on placebo.
• Hypertension (high blood pressure): 15.7% of patients on Efruxifermin experienced this, compared to 2.3% on placebo.
• Abdominal pain: 15.7% of patients on Efruxifermin experienced this, compared to 11.6% on placebo.

These side effects were observed in a trial with 83 patients receiving Efruxifermin.

Clinical Trial Results

Clinical trials have evaluated Efruxifermin in non-cirrhotic patients with nonalcoholic steatohepatitis (NASH), also known as metabolic dysfunction-associated steatohepatitis (MASH). The study, NCT04767529, investigated the effects of Efruxifermin 28 mg and 50 mg doses compared to placebo.

Resolution of Steatohepatitis and Fibrosis Improvement

At Week 96, 26 participants receiving Efruxifermin 50 mg achieved resolution of steatohepatitis without worsening of liver fibrosis, compared to 16 participants on Efruxifermin 28 mg, and 6 participants on placebo. At Week 24, 18 participants on Efruxifermin 28 mg and 16 participants on Efruxifermin 50 mg achieved this outcome, versus 8 participants on placebo.

Liver Fibrosis Improvement

Improvement in liver fibrosis by at least one stage was observed in 21 participants on Efruxifermin 50 mg at Week 24, and 14 participants at Week 96. For Efruxifermin 28 mg, 15 participants showed improvement at Week 24, and 12 participants at Week 96. In comparison, 9 participants on placebo showed improvement at both Week 24 and Week 96.

Reduction in Liver Fat and Stiffness

Patients treated with Efruxifermin experienced reductions in hepatic fat fraction. At Week 24, the average hepatic fat reduction was -11.2 percentage points for Efruxifermin 50 mg and -8.8 percentage points for Efruxifermin 28 mg, compared to -1.9 percentage points for placebo. At Week 96, these reductions were -8.3 percentage points (50 mg) and -6.3 percentage points (28 mg), versus -2.5 percentage points for placebo.

Liver stiffness, measured in kPa, also improved. At Week 24, liver stiffness decreased by -7.2 kPa with Efruxifermin 50 mg and -4.0 kPa with Efruxifermin 28 mg, compared to -0.6 kPa with placebo. At Week 96, the decreases were -4.2 kPa (50 mg) and -2.9 kPa (28 mg), versus -0.8 kPa with placebo.

Metabolic Improvements

Efruxifermin treatment led to improvements in markers of insulin resistance. The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) score decreased by -5.6 units for Efruxifermin 50 mg and -4.1 units for Efruxifermin 28 mg at Week 24, while placebo showed an increase of 0.7 units. At Week 96, HOMA-IR decreased by -5.5 units (50 mg) and -4.7 units (28 mg), compared to a decrease of -1.3 units for placebo.

Additionally, patients on Efruxifermin 50 mg experienced an average body weight reduction of -3.5 kg at Week 24 and -3.0 kg at Week 96. Patients on Efruxifermin 28 mg had a reduction of -0.2 kg at Week 24 and -0.3 kg at Week 96. Placebo patients had reductions of -0.6 kg at Week 24 and -1.5 kg at Week 96.

Currently Recruiting Trials

Where to Participate

• San Antonio, Texas
• Houston, Texas
• Dallas, Texas
• Tucson, Arizona
• Richmond, Virginia
• New York, New York
• Austin, Texas
• San Francisco, California
• Waco, Texas
• Philadelphia, Pennsylvania

Development Timeline