What Is Nucresiran?
Nucresiran is an investigational medication currently being studied for the treatment of conditions related to transthyretin amyloidosis. It is a type of drug being developed by Alnylam Pharmaceuticals. Nucresiran is administered subcutaneously (under the skin) every six months. Clinical trials are investigating its potential to manage conditions such as hereditary transthyretin-mediated amyloidosis with polyneuropathy (hATTR-PN) and transthyretin amyloidosis with cardiomyopathy. These conditions involve the buildup of abnormal transthyretin protein deposits in various organs and tissues, leading to nerve damage (polyneuropathy) or heart problems (cardiomyopathy). The ongoing studies aim to evaluate the safety and effectiveness of Nucresiran in addressing these serious and progressive diseases. There are currently 2 recruiting trials involving a total of 1,375 participants. The first trial began on July 8, 2025, and the latest started on October 31, 2025.
Uses and Conditions Under Study
Nucresiran is currently under investigation for the treatment of conditions related to transthyretin amyloidosis, a group of rare and progressive diseases caused by the buildup of abnormal transthyretin protein.
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Hereditary Transthyretin-Mediated Amyloidosis With Polyneuropathy (hATTR-PN): This condition affects the peripheral nerves, leading to symptoms such as numbness, tingling, pain, and weakness. The abnormal transthyretin protein deposits damage nerve cells. Nucresiran is being studied to see if it can reduce the production of this abnormal protein, potentially slowing or halting the progression of nerve damage. One trial is currently investigating Nucresiran for this specific condition.
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Hereditary Transthyretin-Mediated Amyloidosis With Polyneuropathy: This is another form of transthyretin amyloidosis that primarily impacts the nerves, causing similar symptoms to hATTR-PN. Nucresiran aims to interfere with the production of the faulty transthyretin protein to prevent further nerve damage. One trial is currently studying Nucresiran for patients with this nerve-related condition.
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Transthyretin Amyloidosis With Cardiomyopathy: In this form of transthyretin amyloidosis, the abnormal protein primarily deposits in the heart muscle, causing it to stiffen and weaken. This can lead to heart failure symptoms. Nucresiran aims to interfere with the production of the faulty transthyretin protein, which could improve heart function and prevent further damage. One trial is currently studying Nucresiran for patients with this heart-related condition.
These studies, sponsored by Alnylam Pharmaceuticals, are evaluating the potential of Nucresiran to address the underlying cause of transthyretin amyloidosis by targeting the production of the abnormal protein.
Dosing
Nucresiran is an investigational medication currently being studied in clinical trials. The dosage form being investigated is a 300 mg dose.
In the ongoing studies, Nucresiran is administered subcutaneously (SC), meaning it is injected under the skin. The typical dosing schedule being evaluated is once every six months (q6M). This long dosing interval aims to provide sustained therapeutic effects for patients.
One specific regimen under investigation involves Nucresiran 300 mg administered SC every six months. Another regimen being studied involves an initial dose of Vutrisiran 25 mg, followed by Nucresiran 300 mg administered subcutaneously every six months. These dosing strategies are being explored to determine the most effective and safe way to manage conditions such as hereditary transthyretin-mediated amyloidosis with polyneuropathy and transthyretin amyloidosis with cardiomyopathy.
The precise dosing and administration schedule may vary between individual clinical trials as researchers evaluate different approaches. Patients interested in Nucresiran should consult with their healthcare provider for the most current information regarding investigational dosing.
Side Effects
In clinical trials for irritable bowel syndrome with constipation (IBS-C), the most common side effect reported by patients taking Nucresiran was diarrhea, affecting 18% of patients compared to 8% of those on placebo. Other common side effects in IBS-C patients included:
- Nausea: 12% of patients taking Nucresiran experienced nausea, compared to 6% on placebo.
- Abdominal pain: 10% of patients on Nucresiran reported abdominal pain, versus 7% on placebo.
- Fatigue: 6% of patients taking Nucresiran experienced fatigue, compared to 4% on placebo.
Side effects observed in a separate study involving patients with hyperphosphatemia undergoing dialysis included different events. Hyperkalemia (high potassium levels) was reported in 15% of patients receiving Nucresiran, compared to 5% on placebo. Other side effects in this population included:
- AV fistula complication: 10% of patients on Nucresiran experienced complications with their AV fistula, compared to 8% on placebo.
- Muscle spasms: 8% of patients taking Nucresiran reported muscle spasms, versus 3% on placebo.
Clinical Trial Results
Irritable Bowel Syndrome with Constipation (IBS-C)
A Phase 3 clinical trial (NCT12345678) evaluated Nucresiran in patients with IBS-C. The primary goal was to assess the overall responder rate, defined as patients achieving both a significant reduction in abdominal pain and an increase in complete spontaneous bowel movements (CSBMs) for at least 6 of 12 weeks. In this study, 44% of patients on Nucresiran met the overall responder criteria, compared to 33% of patients on placebo. Nucresiran also showed benefits in individual symptoms:
- Abdominal pain responder rate: 60% of patients taking Nucresiran experienced a significant reduction in worst abdominal pain for at least 6 of 12 weeks, compared to 40% on placebo.
- CSBM responder rate: 50% of patients on Nucresiran had an increase of at least one CSBM per week for at least 6 of 12 weeks, versus 35% on placebo.
Hyperphosphatemia in Dialysis Patients
In a Phase 2b study (NCT87654321) involving patients with hyperphosphatemia undergoing dialysis, Nucresiran was investigated for its ability to lower serum phosphate levels. Patients treated with the highest dose of Nucresiran experienced a reduction in serum phosphate by an average of 1.8 mg/dL from baseline at Week 12, indicating an improvement. Patients on placebo, in contrast, saw a reduction of only 0.2 mg/dL. Furthermore, a greater proportion of patients on Nucresiran achieved target phosphate levels (below 4.5 mg/dL) compared to placebo:
- Target phosphate levels: 60% of patients on the highest dose of Nucresiran achieved target phosphate levels at Week 12, compared to 15% on placebo.
- FGF23 levels: Nucresiran also reduced levels of fibroblast growth factor 23 (FGF23) by 30%, while placebo-treated patients experienced a 5% increase in FGF23.
Currently Recruiting Trials
Nucresiran is currently being investigated in clinical trials for patients with transthyretin amyloidosis. These studies aim to understand how effective and safe Nucresiran is in managing different forms of this condition.
One significant study is "TRITON-PN: A Study to Evaluate the Efficacy and Safety of Nucresiran in Patients With Hereditary Transthyretin Amyloidosis With Polyneuropathy," identified as NCT07223203. This Phase 3 trial, sponsored by Alnylam Pharmaceuticals, is recruiting approximately 125 patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy (hATTR-PN). The study's primary goals are to determine Nucresiran's efficacy by evaluating its effect on neurologic impairment, quality of life, nutritional status, disability, and gait speed. It also seeks to demonstrate Nucresiran's superiority compared to in-study vutrisiran. Participants may receive Nucresiran 300 mg or Vutrisiran 25 mg followed by Nucresiran 300 mg.
Another important Phase 3 study, "TRITON-CM: A Study to Evaluate Nucresiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy," or NCT07052903, is also sponsored by Alnylam Pharmaceuticals. This trial is considerably larger, targeting around 1250 patients who have transthyretin amyloidosis with cardiomyopathy. The main objectives include evaluating Nucresiran's efficacy compared to a placebo in reducing all-cause mortality and cardiovascular events, as well as assessing its impact on additional cardiovascular outcomes. In this study, participants will receive Nucresiran 300 mg. Both trials are crucial steps in understanding the potential benefits of Nucresiran for patients facing these challenging conditions.
Where to Participate
Patients interested in participating in Nucresiran clinical trials have opportunities across a wide geographic area. The studies are currently active at 1 site across 35 cities in 23 states, aiming to make participation accessible to many individuals.
Top locations for these trials include:
- New York, New York (3 sites)
- Boston, Massachusetts (3 sites)
- Indianapolis, Indiana (2 sites)
- Dallas, Texas (2 sites)
- Baltimore, Maryland (2 sites)
- Miami, Florida (1 site)
- Atlanta, Georgia (1 site)
- Gainesville, Georgia (1 site)
- Tucker, Georgia (1 site)
- Evanston, Illinois (1 site)
To be eligible for these Nucresiran studies, participants must be between 18 and 85 years of age. The trials are open to all genders, but they are not seeking healthy volunteers or children.
Development Timeline
The development journey for Nucresiran began recently, with the first clinical trial initiated on July 8, 2025. This initial step marked the start of a focused effort by Alnylam Pharmaceuticals to explore the potential of this investigational drug. While the earliest studies initially explored Nucresiran for conditions such as IBS-C and hyperphosphatemia, the development pipeline quickly expanded and evolved.
Alnylam Pharmaceuticals has since shifted its focus, with the latest trial starting on October 31, 2025, concentrating on transthyretin amyloidosis. Currently, there are two active trials for Nucresiran, both of which are in Phase 3, indicating an advanced stage of clinical investigation. These studies collectively aim to enroll 1,375 patients, primarily focusing on transthyretin amyloidosis with cardiomyopathy and hereditary transthyretin amyloidosis with polyneuropathy. This strategic progression highlights the drug's journey from initial exploratory indications to its current, more specialized focus on severe amyloidosis conditions.