What Is ponsegromab?
ponsegromab is an investigational drug currently being studied in clinical trials. It is administered as a subcutaneous injection. While the specific mechanism of action is still under investigation, studies are exploring its potential effects in various conditions. The drug is being developed by Pfizer.
As an investigational medication, ponsegromab is not yet approved for any specific use by regulatory authorities. Clinical trials are evaluating its safety and effectiveness across a range of health issues, including conditions associated with weight loss, appetite changes, and certain types of cancer.
Uses and Conditions Under Study
ponsegromab is currently being investigated in clinical trials for several conditions, with a total of four trials having enrolled 1,642 participants. These studies aim to understand how the drug might help patients with different health challenges.
- Cancer-Related Conditions: ponsegromab is being studied in patients with various cancers, including Colorectal Cancer (1 trial), Metastatic Pancreatic Ductal Adenocarcinoma (1 trial), Non-small Cell Lung Cancer (1 trial), and Pancreatic Cancer (1 trial). These trials are exploring the drug's potential role in managing cancer or its associated symptoms.
- Cachexia and Loss of Appetite: Two trials are investigating ponsegromab for Cachexia, a severe wasting syndrome often seen in chronic illness, and one trial for Loss of Appetite. These studies aim to determine if the drug can help improve body weight and appetite in affected individuals.
- Fatigue: One trial is exploring ponsegromab's effect on Fatigue, a common and often debilitating symptom that can occur with many chronic conditions, including cancer and heart failure.
- Heart Failure: One trial is also evaluating ponsegromab in patients with Heart Failure. This research seeks to understand if the drug can offer benefits for individuals living with this chronic heart condition.
- Healthy Participants: One trial included Healthy participants. Studies involving healthy individuals are typically conducted to assess the drug's safety, how it is absorbed, distributed, metabolized, and excreted by the body (pharmacokinetics), and to establish a baseline for comparison with patient populations.
Dosing
ponsegromab is administered as a subcutaneous injection. Clinical trials have explored various dosing strategies to determine the most effective and safest amounts for different patient populations and conditions.
Studies have investigated a range of doses, including:
- Low, Medium, and High Doses: Trials have evaluated ponsegromab at low, medium, and high dose levels. These different strengths were studied in various cohorts, including main cohorts (Cohort A), open-label pharmacokinetic (PK) cohorts (Cohort B), and optional cohorts (Cohort C and Cohort D).
- Double-Blind Treatment: Many studies utilized a double-blind design, where neither the participants nor the researchers knew whether the participant was receiving ponsegromab or a placebo. This design helps ensure unbiased results.
- Open-Label Treatment: Some studies included an open-label phase, where all participants and researchers were aware that ponsegromab was being administered, often following an initial double-blind period.
The specific dosing regimen, including the frequency and duration of treatment, is still under investigation in ongoing and completed clinical trials.
Side Effects
The most common side effect reported in clinical trials for ponsegromab was cardiac failure, which occurred in 15.6% of patients taking ponsegromab, compared to 14.6% of patients taking a placebo. Other common side effects included:
- Anemia: 8.5% of patients taking ponsegromab experienced anemia, compared to 8.9% on placebo.
- Diarrhea: 6.8% of patients on ponsegromab experienced diarrhea, compared to 7.8% on placebo.
- Hypokalemia (low potassium levels): 6.0% on ponsegromab compared to 3.7% on placebo.
- Hyperkalemia (high potassium levels): 5.8% on ponsegromab compared to 2.5% on placebo.
- Upper respiratory tract infection: 4.8% on ponsegromab compared to 4.5% on placebo.
- Urinary tract infection: 3.8% on ponsegromab compared to 2.9% on placebo.
- Oedema peripheral (swelling in the limbs): 2.8% on ponsegromab compared to 1.2% on placebo.
- Asthenia (lack of energy or physical weakness): 2.5% on ponsegromab compared to 0.8% on placebo.
Clinical Trial Results
Ponsegromab in Heart Failure (NCT05492500)
In a study of people with heart failure, patients receiving ponsegromab 300 mg showed an improvement in exercise capacity. At Week 22, these patients walked an average of 15.40 meters further in a 6-minute walk test from their baseline, compared to 11.92 meters further for those on placebo. Regarding overall heart failure symptoms and quality of life (measured by the Kansas City Cardiomyopathy Questionnaire-23 Total Symptom Score), 56.7% of patients on ponsegromab 300 mg experienced a clinically
Currently Recruiting Trials
Ponsegromab is currently being investigated in clinical trials to understand its potential benefits for patients. These studies are crucial steps in determining if ponsegromab can be a safe and effective treatment option for various conditions.
One significant study, NCT06989437, is actively recruiting participants. This trial, sponsored by Pfizer, is designed to learn about ponsegromab in adults who have pancreatic cancer that has spread (metastatic pancreatic ductal adenocarcinoma) and are experiencing significant body weight loss and fatigue, a condition known as cachexia. Researchers aim to compare the efficacy, safety, and tolerability of ponsegromab when given alongside standard systemic chemotherapy, versus chemotherapy combined with a placebo. Participants will receive either a lower or higher dose of ponsegromab treatment, or a placebo, in a double-blind manner, meaning neither the patient nor the doctor will know which treatment is being administered.
This study is a combined Phase 2/Phase 3 trial, indicating it is evaluating both the effectiveness and safety of the drug on a larger scale. The trial plans to enroll approximately 982 adult participants, all aged 18 years or older, who meet specific criteria related to their cancer and overall health. Healthy volunteers and children are not eligible for this particular study, as it focuses specifically on patients living with metastatic pancreatic cancer and cachexia.
Where to Participate
The clinical trial for ponsegromab, NCT06989437, has a broad reach across the United States, with study sites in 16 states, covering 28 cities and a total of 42 locations. This wide network aims to make participation accessible to eligible individuals.
Top participating locations include:
- Lexington, Kentucky (4 sites)
- Baltimore, Maryland (4 sites)
- Omaha, Nebraska (3 sites)
- Portland, Oregon (3 sites)
- Reno, Nevada (3 sites)
- Birmingham, Alabama (2 sites)
- Decatur, Illinois (2 sites)
- Los Angeles, California (2 sites)
- Washington D.C., District of Columbia (2 sites)
- Honolulu, Hawaii (2 sites)
Eligibility for this study is limited to adults aged 18 years and older. All genders are welcome to participate. It is important to note that healthy volunteers and children are not eligible for this trial, as it is specifically designed for patients with metastatic pancreatic cancer and cachexia.
Development Timeline
The journey of ponsegromab began on August 8, 2022, when the first clinical trial was initiated. Since then, the development program for ponsegromab, driven entirely by Pfizer, has expanded significantly. A total of 4 clinical trials have been conducted or are ongoing, with an overall enrollment target of 1,642 participants across all studies.
Initially, ponsegromab was explored for conditions such as Irritable Bowel Syndrome with Constipation (IBS-C) and hyperphosphatemia. Over time, the research pipeline broadened, reflecting a deeper understanding of the drug's potential mechanisms. Subsequent studies have investigated ponsegromab for a wider range of conditions, including Fatigue, Heart Failure, and Loss of Appetite, as well as in healthy volunteers to understand its basic effects.
The development has progressed through various phases, starting with a Phase 1 trial to assess initial safety and dosage. This was followed by two Phase 2 trials, which further evaluated effectiveness and safety in specific patient groups. Currently, the program includes a combined Phase 2/Phase 3 trial, marking a significant step towards potential regulatory approval. The latest trial is projected to conclude by May 25, 2025, focusing on serious conditions like Metastatic Pancreatic Ductal Adenocarcinoma, Non-small Cell Lung Cancer, and Pancreatic Cancer, particularly addressing cachexia associated with these advanced cancers.