What Is Cemdisiran?
Cemdisiran is an investigational drug currently being studied in clinical trials. It is administered as an injection, either subcutaneously (under the skin) or intravenously (into a vein), depending on the specific study protocol. Cemdisiran is being developed to treat a range of conditions, often in combination with another investigational drug, Pozelimab.
Research into Cemdisiran began with the first clinical trial on October 6, 2017. To date, a total of 15 clinical trials have been conducted or are ongoing, involving 1,825 participants. Of these, 4 trials are currently recruiting new participants, while 4 trials have been completed. The latest trial is projected to conclude on September 4, 2025. Major sponsors of these trials include Regeneron Pharmaceuticals and Alnylam Pharmaceuticals.
Uses and Conditions Under Study
Cemdisiran is being investigated for several conditions, primarily focusing on disorders related to the complement system and inflammatory processes. The conditions under study include:
- Blood Disorders: Cemdisiran is most extensively studied for Paroxysmal Nocturnal Hemoglobinuria (PNH), a rare, life-threatening blood disorder characterized by the destruction of red blood cells. Seven trials are investigating Cemdisiran for PNH. It is also being studied for Atypical Hemolytic Uremic Syndrome (aHUS), another rare blood disorder that causes abnormal blood clots in small blood vessels, with 2 trials exploring its potential.
- Kidney Disorders: The drug is being investigated for various kidney conditions, including IgA Nephropathy (IgAN), Glomerulonephritis, IgA, and Berger Disease. These conditions involve inflammation and damage to the kidney's filtering units. Three trials collectively focus on these related kidney disorders.
- Eye Conditions: Cemdisiran is being explored for its potential in treating Age-related Macular Degeneration (AMD) and Geographic Atrophy (GA), which are progressive eye diseases that can lead to severe vision loss. Two trials are dedicated to these ocular conditions.
- Muscle and Inflammatory Conditions: Research is also underway for Idiopathic Inflammatory Myopathies and Sporadic Inclusion Body Myositis (sIBM), which are chronic inflammatory diseases affecting the muscles. Two trials are investigating Cemdisiran for these conditions.
- Healthy Volunteers: In addition to specific conditions, Cemdisiran has been studied in 2 trials involving healthy volunteers. These studies typically assess the drug's safety, how it moves through the body (pharmacokinetics), and how it affects the body (pharmacodynamics) in individuals without the target disease.
Dosing
Cemdisiran is administered as an injection. Clinical trials have investigated both subcutaneous (SC) and intravenous (IV) routes of administration. The specific dosage and frequency vary depending on the study and the condition being investigated.
In some studies, Cemdisiran has been administered as a monotherapy. However, it is also frequently studied in combination with Pozelimab. One specific regimen studied involves patients receiving Pozelimab 200 mg/Cemdisiran 200 mg via subcutaneous injections. This combination is typically administered every 4 weeks for an extended period, such as 104 weeks. Other combination regimens include Pozelimab given every 2 weeks or every 4 weeks alongside Cemdisiran. The dosage forms studied include various combinations of Pozelimab and Cemdisiran, as well as Cemdisiran monotherapy treatment groups. Specific patient populations, such as PNH Transition Patients and C5 Polymorphism Patients, have also been included in dosing studies.
Side Effects
In a clinical trial involving 74 patients taking Cemdisiran, the most common side effect was injection site reaction. Overall, side effects were reported by patients taking Cemdisiran at the following rates compared to patients taking a placebo:
- Injection site reaction: 43.2% of patients taking Cemdisiran experienced this, compared to 41.2% on placebo.
- Peripheral edema (swelling): 13.5% of patients taking Cemdisiran experienced this, compared to 11.8% on placebo.
- Rash: 12.2% of patients taking Cemdisiran experienced this, compared to 5.9% on placebo.
- Upper respiratory tract infection: 10.8% of patients taking Cemdisiran experienced this, compared to 0.0% on placebo.
- Urticaria (hives): 9.5% of patients taking Cemdisiran experienced this, compared to 0.0% on placebo.
- Increased alanine aminotransferase (a liver enzyme): 9.5% of patients taking Cemdisiran experienced this, compared to 5.9% on placebo.
- Increased aspartate aminotransferase (a liver enzyme): 9.5% of patients taking Cemdisiran experienced this, compared to 5.9% on placebo.
- Oropharyngeal pain (sore throat): 8.1% of patients taking Cemdisiran experienced this, compared to 0.0% on placebo.
Clinical Trial Results
Cemdisiran has been studied in clinical trials for conditions such as IgA Nephropathy and Paroxysmal Nocturnal Hemoglobinuria (PNH).
IgA Nephropathy (IgAN)
A study (NCT03841448) evaluated Cemdisiran in adults with IgAN. After 32 weeks, patients treated with Cemdisiran showed a geometric mean urine protein-to-creatinine ratio (UPCR) of 0.729 gram per gram (g/g), which indicates less protein in the urine, compared to 1.344 g/g for those on placebo. This suggests an improvement in kidney function markers. The study also found that 22.7% of patients receiving Cemdisiran achieved a greater than 50% reduction in 24-hour proteinuria, a key measure of kidney disease, while no patients on placebo achieved this. Additionally, 22.7% of patients on Cemdisiran achieved partial clinical remission, compared to 0% on placebo.
Paroxysmal Nocturnal Hemoglobinuria (PNH)
Cemdisiran was studied in combination with Pozelimab for the treatment of PNH. In a study (NCT04811716) of adults with PNH who had not previously received Pozelimab monotherapy, patients received a combination of Pozelimab and Cemdisiran. After 28 weeks, 100% of patients receiving Pozelimab every four weeks plus Cemdisiran achieved transfusion avoidance, meaning they did not require red blood cell transfusions, compared to 83.3% of those receiving Pozelimab every two weeks plus Cemdisiran. Hemoglobin stabilization was achieved by 91.7% of patients on the every four-week regimen and 75.0% on the every two-week regimen. Furthermore, 0.0% of patients on the every four-week regimen experienced breakthrough hemolysis, compared to 8.3% on the every two-week regimen.
Another study (NCT04888507) investigated the combination therapy in adult PNH patients who switched from Eculizumab. In this open-label extension period (OLEP) lasting 52 weeks, 100% of participants maintained adequate control of hemolysis. Also, 80.0% of participants were transfusion-free and 80.0% achieved hemoglobin stabilization. No participants experienced breakthrough hemolysis during this period.
A third study (NCT05131204) comparing Pozelimab and Cemdisiran combination therapy to continued standard-of-care (Eculizumab or Ravulizumab) for PNH reported no treatment discontinuations due to adverse events in either group. One event of special interest occurred in the Pozelimab and Cemdisiran group, and no serious adverse events were reported in either group.
Currently Recruiting Trials
Cemdisiran is currently being investigated in several clinical trials, often in combination with another experimental drug, pozelimab. These studies aim to explore new treatment options for a range of conditions.
One ongoing Phase 3 study, NCT07154745, is evaluating the combination of pozelimab and cemdisiran in adult patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) whose current treatment is not working efficiently. Researchers are seeking a more effective approach for this blood disorder, with an enrollment target of 35 participants. Another Phase 3 study, NCT05744921, also focuses on PNH, assessing the long-term safety and effectiveness of the pozelimab and cemdisiran combination. This study aims to enroll 202 adult patients, including those transitioning from other PNH treatments and those with specific genetic markers.
For eye conditions, a large Phase 3 trial, NCT06541704, is investigating cemdisiran for Geographic Atrophy (GA) caused by Age-related Macular Degeneration (AMD). This study explores both pozelimab in combination with cemdisiran, and cemdisiran as a standalone treatment. It plans to enroll up to 975 adult participants.
Additionally, an early-phase study, NCT06479863, is evaluating the efficacy and safety of pozelimab and cemdisiran combination therapy for Sporadic Inclusion Body Myositis (sIBM). This Early Phase 1 trial, targeting 10 patients, seeks to understand how the combination therapy works for this rare muscle disease.
Where to Participate
Clinical trials for Cemdisiran are being conducted across a wide geographic area, with studies active at 149 sites in 120 cities across 33 states. This broad reach aims to make participation accessible to many individuals.
Top participating locations include:
- Austin, Texas (5 sites)
- San Antonio, Texas (4 sites)
- New York, New York (4 sites)
- Los Angeles, California (3 sites)
- Sacramento, California (3 sites)
- Portland, Oregon (3 sites)
- Phoenix, Arizona (3 sites)
- Chicago, Illinois (3 sites)
- Dallas, Texas (3 sites)
- Beverly Hills, California (2 sites)
Eligibility criteria for these studies generally require participants to be between 18 and 85 years of age. All genders are welcome to participate. These trials are specifically designed for patients with the conditions being studied, and therefore do not enroll healthy volunteers or children.
Development Timeline
The development journey for Cemdisiran began with its first clinical trial on October 6, 2017. Since then, the drug has been investigated in a total of 15 trials, enrolling 1,825 participants as researchers explore its potential across various conditions.
Regeneron Pharmaceuticals has been a primary driver of Cemdisiran's development, sponsoring 11 of these trials. Other organizations, including Alnylam Pharmaceuticals, Austin Neuromuscular Center, and the Mario Negri Institute for Pharmacological Research, have also contributed to its study.
Cemdisiran's pipeline has shown significant expansion over time. Initial investigations focused on conditions such as Irritable Bowel Syndrome with Constipation (IBS-C) and hyperphosphatemia. The research has since broadened considerably to include a range of rare and complex diseases. These newer indications include Atypical Hemolytic Uremic Syndrome, Geographic Atrophy (GA), Glomerulonephritis, IgA Nephropathy (IgAN), Age-related Macular Degeneration (AMD), Sporadic Inclusion Body Myositis (sIBM), Berger Disease, and Generalized Myasthenia Gravis. The latest trial for Cemdisiran is projected to start on September 4, 2025, indicating ongoing commitment to its research. The trials span various stages of development, with 6 studies reaching Phase 3, 5 in Phase 2, and 2 in Phase 1, reflecting a comprehensive and progressive research program.