What Is Leronlimab?
Leronlimab is an investigational drug, also known as PRO 140. It is a humanized IgG4κ monoclonal antibody that targets Chemokine Receptor type 5 (CCR5). This means leronlimab is a type of protein that is designed to specifically attach to and block the CCR5 receptor on certain cells. By blocking CCR5, leronlimab may interfere with various disease processes, including inflammation and the spread of cancer cells.
Leronlimab is currently under development to potentially treat a range of different diseases. These include various types of cancer such as metastatic colorectal cancer (mCRC) and triple-negative breast cancer (TNBC), as well as conditions like Coronavirus Disease 2019 (COVID-19), Nonalcoholic Steatohepatitis (NASH), and Mild Cognitive Impairment (MCI) due to Alzheimer's Disease.
Uses and Conditions Under Study
Leronlimab is being studied in a total of 13 clinical trials for its potential to treat several conditions. These trials are investigating how leronlimab might help patients by targeting the CCR5 receptor, which plays a role in immune responses and disease progression.
- Coronavirus Disease 2019 (COVID-19) and COVID-19 Pneumonia: Leronlimab is being investigated in 5 trials for patients with COVID-19. The CCR5 receptor is involved in the movement of immune cells and inflammation, which are key aspects of severe COVID-19. Researchers are exploring if leronlimab can help reduce inflammation and improve outcomes in these patients.
- Various Cancers: Leronlimab is under investigation for several types of cancer, including Colorectal Cancer, Metastatic Colorectal Cancer (mCRC), Metastatic Triple-Negative Breast Carcinoma, and other Solid Tumors. In 6 trials, researchers are studying leronlimab's potential to inhibit tumor growth and metastasis, as CCR5 can be involved in cancer cell migration and survival. One trial specifically focuses on Microsatellite Stable tumors.
- Mild Cognitive Impairment (MCI) Due to Alzheimer's Disease: In 1 trial, leronlimab is being studied in participants over 50 years old with Alzheimer's disease or MCI due to Alzheimer's. While leronlimab is considered safe in other diseases like HIV and certain cancers, this study aims to evaluate its safety and potential benefits in cognitive impairment.
- Nonalcoholic Steatohepatitis (NASH): Leronlimab is also being investigated in 1 trial for NASH, a liver condition characterized by inflammation and liver cell damage. The role of CCR5 in liver inflammation and fibrosis makes leronlimab a potential therapeutic target for this condition.
Dosing
Leronlimab has been studied in various doses and administration methods. It is administered as a subcutaneous (SC) injection, meaning it is injected under the skin. The most commonly studied doses for leronlimab include 350 mg, 525 mg, and 700 mg.
In some studies, leronlimab has been given as a weekly subcutaneous injection. For example, one regimen involved a 700 mg first dose followed by weekly 350 mg doses. Other trials have explored weekly doses of 350 mg, 525 mg, or 700 mg.
Leronlimab has also been investigated in combination with other medications. These combinations include leronlimab with Trifluridine + Tipiracil (TAS-102) + Bevacizumab, and leronlimab in combination with Regorafenib. The specific dosing and combination regimens vary depending on the condition being studied and the phase of the clinical trial.
Side Effects
In a clinical trial involving 348 patients receiving Leronlimab or a placebo, most side effects were reported less frequently in patients treated with Leronlimab. The most common side effects reported in this trial included:
- Respiratory disorders, such as breathing difficulties, affected 25.6% of patients on Leronlimab compared to 26.4% on placebo.
- Infections and infestations occurred in 20.7% of patients taking Leronlimab, versus 27.2% on placebo.
- Metabolic and nutrition disorders were reported by 16.7% of Leronlimab patients, compared to 16.8% on placebo.
- Cardiac (heart) disorders affected 13.2% of patients on Leronlimab, while 16.8% on placebo experienced them.
- Renal and urinary disorders were seen in 10.1% of Leronlimab patients, versus 12.0% on placebo.
- Gastrointestinal disorders, such as stomach or bowel issues, occurred in 6.0% of patients on Leronlimab, compared to 14.4% on placebo.
One notable exception was an increase in C-reactive protein (a marker of inflammation), which was observed in 12.8% of patients taking Leronlimab across three trials (n=141), compared to 7.0% of patients on placebo.
Clinical Trial Results
Metastatic Triple-Negative Breast Cancer (mTNBC)
A Phase 1 study (NCT03838367) investigated Leronlimab combined with carboplatin in patients with CCR5+ mTNBC. This trial primarily focused on determining the maximum tolerated dose (MTD) and evaluating the safety of the combination. The maximum tolerated dose of Leronlimab was found to be 700 mg when combined with carboplatin.
Mild to Moderate COVID-19
In a study (NCT04343651) evaluating Leronlimab for mild to moderate COVID-19, patients receiving 700 mg Leronlimab showed a mean reduction in their National Early Warning Score 2 (NEWS2) of -0.3 to -0.4, indicating an improvement in clinical status. Patients on placebo showed a mean change of -0.2 to 0.0. The average duration of mechanical ventilation supply was slightly shorter in the Leronlimab group at 0.2 days, compared to 0.4 days for placebo. No deaths were reported in either the Leronlimab or placebo groups by Day 14.
Severe or Critical COVID-19
A separate study (NCT04
Currently Recruiting Trials
Leronlimab is currently being investigated in clinical trials to understand its potential benefits across various conditions. These trials are essential for gathering more information about the drug's safety and effectiveness.
One notable trial, NCT07553338, is a Phase 2 study titled "Safety Assessment of Leronlimab and Its Effect on Brain Inflammation in Alzheimer's Disease." Sponsored by Weill Medical College of Cornell University, this study aims to evaluate leronlimab in individuals diagnosed with Mild Cognitive Impairment (MCI) due to Alzheimer's Disease or Alzheimer's Disease itself. The trial is designed to administer leronlimab to 20 participants who are over 50 years old. While leronlimab has shown a safety profile in other conditions like Human Immunodeficiency Virus (HIV) and certain cancers, this study specifically focuses on its impact on brain inflammation in the context of Alzheimer's disease.
Where to Participate
Participation in clinical trials for leronlimab is currently available at a single location for the recruiting study. This site is located in New York, New York.
For individuals interested in participating in the Alzheimer's disease trial, specific eligibility criteria apply. Participants must be between the ages of 50 and 50 years, and all genders are welcome. The study is not open to healthy volunteers or children, focusing specifically on individuals with Mild Cognitive Impairment due to Alzheimer's Disease or Alzheimer's Disease.
Development Timeline
The journey of leronlimab in clinical development began on February 12, 2019, with the initiation of its first clinical trial. Since then, a total of 13 trials have been conducted or are ongoing, involving approximately 1,753 participants. The primary sponsor driving much of this research has been CytoDyn, Inc., which has sponsored 10 trials, alongside contributions from Hospital Israelita Albert Einstein and Weill Medical College of Cornell University.
Leronlimab's development initially explored conditions such as Irritable Bowel Syndrome with Constipation (IBS-C) and hyperphosphatemia. Over time, the research pipeline significantly expanded to investigate its potential in various forms of cancer, including Colorectal Cancer, Metastatic Colorectal Cancer (mCRC), Metastatic Triple-Negative Breast Carcinoma, and several other Triple-Negative Breast Cancer (TNBC) indications. Beyond oncology, leronlimab has also been studied for Nonalcoholic Steatohepatitis (NASH) and, more recently, for Mild Cognitive Impairment (MCI) due to Alzheimer's Disease and Alzheimer's Disease. The majority of trials, 8 studies, have progressed to Phase 2, with 2 trials reaching Phase 3, indicating significant advancement in its clinical evaluation. The latest projected completion date for an ongoing trial extends to April 28, 2026, highlighting continued research into this compound.