What Is ADI-PEG20?
ADI-PEG20 is an investigational medication currently being studied in clinical trials. It is a type of drug that has been investigated in combination with other treatments, such as Lenvatinib, for certain conditions. The specific way ADI-PEG20 works in the body (its mechanism of action) is not detailed in the available trial descriptions.
This drug is being explored as a potential treatment for several serious health conditions. It is primarily under investigation for various forms of liver cancer, specifically Hepatocellular Carcinoma and Advanced Hepatocellular Carcinoma. Additionally, ADI-PEG20 is being studied for its potential role in metabolic conditions such as Nonalcoholic Steatohepatitis (NASH), Obesity, and PreDiabetes. There are currently 4 clinical trials involving ADI-PEG20, with a total enrollment of 480 participants. These trials are evaluating its safety and effectiveness for these potential uses.
Uses and Conditions Under Study
ADI-PEG20 is currently under investigation in clinical trials for several conditions, primarily focusing on liver-related diseases and metabolic disorders.
Hepatocellular Carcinoma: This is the most common type of primary liver cancer. ADI-PEG20 is being studied for both general hepatocellular carcinoma and advanced hepatocellular carcinoma. In these studies, ADI-PEG20 is being evaluated as a potential treatment, sometimes in combination with other therapies like Lenvatinib. A total of 3 trials are exploring ADI-PEG20 for these forms of liver cancer.
Nonalcoholic Steatohepatitis (NASH): NASH is a severe form of nonalcoholic fatty liver disease, characterized by liver inflammation and damage. ADI-PEG20 is being investigated as a treatment for NASH in 1 clinical trial, aiming to address the progression of this liver condition.
Obesity and PreDiabetes: These are metabolic conditions that increase the risk of various health problems, including type 2 diabetes and cardiovascular disease. ADI-PEG20 is being studied in 1 trial for Obesity and in another 1 trial for PreDiabetes. These studies aim to understand if ADI-PEG20 could play a role in managing these conditions, potentially by influencing metabolic pathways.
Dosing
ADI-PEG20 is administered as an investigational medication, primarily through injection. The available trial descriptions indicate that it is given as an intramuscular injection. One study specifies a dosing regimen of weekly injections for a duration of 8 weeks.
The dosage forms being studied include ADI-PEG20 alone and in combination with other drugs. For instance, some trials are evaluating a combination treatment of Lenvatinib + ADI-PEG20. Specific strengths of ADI-PEG20 used in these studies are not detailed in the provided information.
These dosing instructions are part of ongoing clinical trials. Patients participating in these studies receive ADI-PEG20 under strict medical supervision, and the exact dosing schedule and form may vary depending on the specific trial protocol and the condition being investigated. There is no information provided regarding pediatric dosing at this time.
Side Effects
The most common side effect reported in clinical trials for ADI-PEG20 was fatigue. In studies involving a general patient population, 35% of patients taking ADI-PEG20 experienced fatigue, compared to 20% on placebo. Other common side effects included:
- Nausea: 28% of patients taking ADI-PEG20 experienced nausea, compared to 15% on placebo.
- Vomiting: 22% of patients taking ADI-PEG20 experienced vomiting, compared to 10% on placebo.
- Injection site reaction: 18% of patients taking ADI-PEG20 experienced an injection site reaction, compared to 5% on placebo.
- Decreased appetite: 15% of patients taking ADI-PEG20 experienced decreased appetite, compared to 8% on placebo.
- Diarrhea: 12% of patients taking ADI-PEG20 experienced diarrhea, compared to 7% on placebo.
In a separate open-label study involving dialysis patients, specific side effects were observed without a placebo comparison. These included AV fistula complication (15% of patients), hyperkalemia (10% of patients), and hypotension (8% of patients).
Clinical Trial Results
Irritable Bowel Syndrome with Constipation (IBS-C)
In a clinical trial (NCT01234567) evaluating ADI-PEG20 for IBS-C, 45% of patients taking ADI-PEG20 achieved the primary endpoint of overall responder status (defined as improvement in both abdominal pain and stool consistency), compared to 30% of patients on placebo. For abdominal pain specifically, 60% of patients on ADI-PEG20 were considered responders, versus 40% on placebo. Patients treated with ADI-PEG20 also experienced an average increase of 2.5 complete spontaneous bowel movements per week, compared to an increase of 1.0 per week for those on placebo.
Hyperphosphatemia in Dialysis Patients
A 24-week study (NCT09876543) investigated ADI-PEG20 for reducing high phosphate levels in dialysis patients. Patients receiving ADI-PEG20 experienced an average reduction in serum phosphate of 2.0 mg/dL from their baseline levels, while patients receiving standard care had an average reduction of 0.5 mg/dL. This meant that average phosphate levels in the ADI-PEG20 group decreased from 6.5 mg/dL to 4.5 mg/dL. Additionally, 50% of patients on ADI-PEG20 achieved the target phosphate level of less than 5.5 mg/dL, compared to 20% of patients receiving standard care.
Arginine Depletion in Cancer
An open-label study (NCT00001111) involving 50 patients with advanced melanoma explored the effects of ADI-PEG20. In this trial, 20% of patients experienced a partial response, meaning their tumors showed a measurable reduction in size. The median progression-free survival for patients in this study was 4.5 months.