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Patisiran

Patisiran is an investigational drug being studied in clinical trials for the treatment of transthyretin-mediated (ATTR) amyloidosis, a rare and serious condition caused by the buildup of abnormal proteins in various organs and tissues. This article summarizes key findings from clinical trials evaluating patisiran’s safety and effectiveness in patients with different forms of ATTR amyloidosis, including those with polyneuropathy and cardiomyopathy.

Table of Contents

What is Patisiran?

Patisiran is a medication used to treat certain types of amyloidosis, a rare and serious condition. It is also known by its brand name ONPATTRO or its research code ALN-TTR02[1][2]. Patisiran is part of a new class of drugs that work by interfering with the production of specific proteins in the body.

What Conditions Does Patisiran Treat?

Patisiran is primarily used to treat the following conditions:

  • Hereditary Transthyretin-mediated (ATTRv) Amyloidosis: This is an inherited condition where abnormal proteins build up in various organs, causing damage[1].
  • Polyneuropathy: This is nerve damage that occurs as part of ATTRv amyloidosis[1].
  • Transthyretin Amyloidosis with Cardiomyopathy (ATTR Amyloidosis with Cardiomyopathy): This is a form of amyloidosis that affects the heart[7].

How Does Patisiran Work?

Patisiran works by reducing the production of a protein called transthyretin (TTR) in the liver. In patients with ATTRv amyloidosis, this protein is abnormal and builds up in various parts of the body, causing damage. By decreasing the amount of TTR produced, patisiran helps to reduce the accumulation of these harmful protein deposits[2].

How is Patisiran Administered?

Patisiran is given as an intravenous (IV) infusion, which means it’s delivered directly into your bloodstream through a vein. The typical dosing schedule is:

  • Once every 3 weeks (q3w)[3]
  • The dose is usually 0.3 milligrams per kilogram (mg/kg) of body weight[2]
  • For patients weighing 100 kg or more, the maximum dose is 30 mg[2]

Before receiving patisiran, patients are typically given premedications to reduce the risk of infusion-related reactions[3].

Efficacy of Patisiran

Clinical trials have shown that patisiran can be effective in treating the symptoms of ATTRv amyloidosis. Some of the benefits observed include:

  • Improved neurological function: Measured by the Neuropathy Impairment Score (NIS), which assesses muscle weakness, sensation, and reflexes[2].
  • Better quality of life: As measured by the Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) questionnaire[2].
  • Improved disability scores: Using the Rasch-Built Overall Disability Scale (R-ODS)[2].
  • Reduced autonomic symptoms: Measured by the Composite Autonomic Symptom Score (COMPASS-31)[2].
  • Improved nutritional status: As indicated by the modified Body Mass Index (mBMI)[2].

Safety and Side Effects

Like all medications, patisiran can cause side effects. The most common side effects reported in clinical trials include:

  • Infusion-related reactions
  • Upper respiratory tract infections
  • Headache
  • Diarrhea

It’s important to note that not everyone experiences side effects, and your doctor will monitor you closely during treatment[2].

Ongoing Research

Patisiran continues to be studied in various clinical trials to further understand its benefits and potential uses. Some areas of ongoing research include:

  • Long-term safety and efficacy in patients with ATTRv amyloidosis[3]
  • Use in patients who have had liver transplants[2]
  • Effectiveness in treating ATTR amyloidosis with cardiomyopathy[7]
  • Comparison with other treatments for ATTRv amyloidosis[8]

These ongoing studies will help researchers and doctors better understand how to use patisiran most effectively and safely in different patient populations.

Aspect Details
Drug Name Patisiran (ALN-TTR02, ONPATTRO)
Mechanism of Action RNA interference (RNAi) therapeutic targeting TTR gene
Administration Intravenous infusion, typically every 3 weeks
Target Conditions Hereditary ATTR amyloidosis with polyneuropathy, ATTR amyloidosis with cardiomyopathy, wild-type ATTR amyloidosis
Key Efficacy Measures mNIS+7, Norfolk QoL-DN, 6MWT, KCCQ-OS, NT-proBNP, echocardiogram parameters
Safety Monitoring Adverse events, serious adverse events, study discontinuations
Notable Findings Improvements in neurological impairment, quality of life, and walking ability; reduction in serum TTR levels
Ongoing Research Long-term safety and efficacy, alternative dosing regimens, expanded patient populations

FAQ

  • What is patisiran and how does it work? Patisiran is an RNA interference (RNAi) therapeutic that targets and silences the TTR gene, reducing the production of abnormal TTR protein that causes ATTR amyloidosis. It is administered as an intravenous infusion.
  • What types of ATTR amyloidosis is patisiran being studied for? Patisiran is being investigated for hereditary ATTR amyloidosis with polyneuropathy, ATTR amyloidosis with cardiomyopathy, and wild-type ATTR amyloidosis.
  • How often is patisiran administered in clinical trials? In most trials, patisiran is administered as an intravenous infusion once every 3 weeks. Some studies are also evaluating less frequent dosing schedules.
  • What are some of the key outcomes being measured in patisiran clinical trials? Key outcomes include changes in neurological impairment scores, quality of life measures, walking ability, cardiac function, and serum TTR levels. Safety and tolerability are also closely monitored.
  • Are there any expanded access programs available for patisiran? Yes, there are expanded access protocols to provide patisiran to eligible patients with hereditary ATTR amyloidosis with polyneuropathy and ATTR amyloidosis with cardiomyopathy who do not qualify for ongoing clinical trials.

Ongoing Clinical Trials on Patisiran

  • Study of Patisiran for Patients with Transthyretin Amyloidosis and Heart Disease

    Not recruiting

    1 1 1
    Investigated diseases:
    Investigated drugs:
    Belgium Czechia Denmark France Italy The Netherlands +2

  • Study on the Effectiveness and Safety of Vutrisiran and Patisiran for Patients with Hereditary Transthyretin Amyloidosis

    Not recruiting

    1 1 1 1
    Investigated diseases:
    Investigated drugs:
    Belgium Bulgaria Cyprus Italy The Netherlands Portugal +1

Glossary

  • ATTR amyloidosis: A rare disease caused by the buildup of abnormal transthyretin (TTR) protein in various organs and tissues, leading to organ dysfunction.
  • Polyneuropathy: Damage to multiple nerves throughout the body, causing symptoms like numbness, tingling, and weakness in the limbs.
  • Cardiomyopathy: A group of diseases affecting the heart muscle, leading to decreased heart function and potential heart failure.
  • Transthyretin (TTR): A protein produced primarily by the liver that transports thyroid hormone and vitamin A in the blood.
  • mNIS+7: Modified Neurologic Impairment Score +7, a composite measure of neurologic impairment used to assess disease progression in ATTR amyloidosis.
  • Norfolk QoL-DN: Norfolk Quality of Life-Diabetic Neuropathy questionnaire, a tool used to measure quality of life in patients with neuropathy.
  • 6-Minute Walk Test (6MWT): A test that measures the distance an individual can walk in 6 minutes, used to assess functional capacity.
  • KCCQ-OS: Kansas City Cardiomyopathy Questionnaire Overall Summary, a measure of health status in patients with heart failure.
  • NT-proBNP: N-terminal prohormone of brain natriuretic peptide, a biomarker used to assess heart failure severity.
  • Echocardiogram: An ultrasound of the heart used to evaluate cardiac structure and function.

References

  1. https://clinicaltrials.gov/study/NCT04201418
  2. https://clinicaltrials.gov/study/NCT03862807
  3. https://clinicaltrials.gov/study/NCT02510261
  4. https://clinicaltrials.gov/study/NCT01617967
  5. https://clinicaltrials.gov/study/NCT05505838
  6. https://clinicaltrials.gov/study/NCT05023889
  7. https://clinicaltrials.gov/study/NCT03997383
  8. https://clinicaltrials.eu/trial/study-on-the-effectiveness-and-safety-of-vutrisiran-and-patisiran-for-patients-with-hereditary-transthyretin-amyloidosis/
  9. https://clinicaltrials.gov/study/NCT02939820
  10. https://clinicaltrials.gov/study/NCT01961921