By Counterforce Health Team —

Onpattro (Patisiran): An RNA Therapy for Hereditary Transthyretin Amyloidosis

Hereditary transthyretin-mediated (hATTR) amyloidosis is a rare and progressive disease that affects multiple organs and nerves throughout the body. For years, treatment options were limited to managing symptoms rather than addressing the root cause.

That changed with the approval of Onpattro® (patisiran) — the first therapy to use RNA interference (RNAi)technology to target and reduce the production of the disease-causing protein at its source.

What Is Onpattro?

Onpattro (patisiran) is a prescription medication approved for the treatment of polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) in adults.

It was the first-ever RNA interference drug approved by the U.S. Food and Drug Administration (FDA) in 2018, marking a revolutionary step in genetic medicine.

Onpattro is administered as an intravenous (IV) infusion, usually once every three weeks in a medical setting.

Understanding hATTR Amyloidosis

What Causes It

Hereditary transthyretin amyloidosis (hATTR) is caused by a mutation in the TTR gene, which makes an abnormal version of a protein called transthyretin (TTR).

Normally, TTR helps transport vitamin A and thyroid hormone in the blood. However, in people with hATTR, the abnormal TTR proteins misfold and form amyloid deposits in tissues and organs — including nerves, the heart, and the gastrointestinal tract.

How It Affects the Body

Over time, these deposits damage nerves and other organs, leading to:

  • Peripheral neuropathy: numbness, tingling, or pain in the hands and feet
  • Autonomic symptoms: dizziness, digestive issues, or urinary problems
  • Cardiac complications: thickened heart muscle, irregular heartbeat, or heart failure

Without treatment, the disease tends to worsen over time and can severely impact quality of life.

How Onpattro Works

Onpattro uses a novel approach known as RNA interference (RNAi) — a natural cellular process that “silences” or “turns off” specific genes responsible for making harmful proteins.

Here’s how it works:

  1. The active ingredient, patisiran, is a small interfering RNA (siRNA) molecule.
  2. It is delivered to liver cells (where TTR is made) via lipid nanoparticles — tiny fat-based particles that protect the RNA and help it enter cells.
  3. Once inside, patisiran binds to the messenger RNA (mRNA) that carries the blueprint for making TTR.
  4. This binding causes the mRNA to be destroyed, reducing the production of both normal and abnormal TTR protein.
  5. With less TTR circulating, amyloid buildup slows or decreases, which can relieve symptoms and improve nerve function.

Essentially, Onpattro helps treat hATTR by reducing the source of the problem — the faulty protein — rather than only managing the damage it causes.

Clinical Evidence

Onpattro’s approval was based on results from the APOLLO Phase 3 clinical trial, which included adults with hATTR amyloidosis with polyneuropathy.

Key findings included:

  • Improved nerve function: Patients treated with Onpattro showed a significant reduction in neuropathy progression compared to placebo.
  • Better quality of life: Improvements were seen in walking ability, daily functioning, and autonomic symptoms.
  • Reduced TTR levels: Onpattro reduced serum TTR concentrations by about 80%.

Many patients also reported improvements in energy, sensory function, and independence in daily activities.

How Onpattro Is Given

  • Form: Intravenous (IV) infusion
  • Frequency: Every three weeks
  • Duration: Each infusion typically lasts about 80 minutes
  • Premedication: Patients receive medications before infusion — such as corticosteroids, acetaminophen, and antihistamines — to reduce the risk of infusion-related reactions.

Treatment is usually administered at a healthcare facility under medical supervision.

Benefits of Onpattro

Patients receiving Onpattro may experience:

  • Slowed or halted progression of nerve damage
  • Improved sensation and mobility
  • Reduced pain and neuropathic symptoms
  • Better autonomic function (e.g., digestion and blood pressure regulation)
  • Enhanced overall quality of life

Importantly, Onpattro addresses the root cause of hATTR by reducing TTR production, rather than only treating symptoms.

Possible Side Effects

Like all medications, Onpattro can cause side effects. The most common include:

  • Infusion-related reactions (flushing, chest discomfort, shortness of breath, back pain, or nausea)
  • Fatigue
  • Headache
  • Upper respiratory infections (such as colds)

These reactions are generally mild to moderate and can be managed by adjusting infusion rates or using premedications.

Less common but potentially serious side effects include:

  • Low vitamin A levels: Because TTR helps carry vitamin A, patients on Onpattro must take a daily vitamin A supplement as directed by their healthcare provider.
  • Liver enzyme changes: Liver function tests are performed periodically during treatment.

Monitoring and Safety

Patients receiving Onpattro will undergo regular monitoring to:

  • Check nerve and heart function
  • Track liver enzyme levels
  • Assess vitamin A status
  • Evaluate treatment response and side effects

Your care team will determine how often these assessments are needed based on your health and treatment response.

Who Can Receive Onpattro

Onpattro is approved for adults with hereditary ATTR amyloidosis who have polyneuropathy (nerve damage).

It is not approved for patients with wild-type (non-hereditary) ATTR amyloidosis or for those whose symptoms are primarily cardiac.

However, ongoing research is exploring its potential use in ATTR amyloidosis with cardiomyopathy, and early studies have shown promising results.

Practical Considerations

  • Treatment commitment: Regular infusions every three weeks are required for ongoing benefit.
  • Lifestyle: Many patients continue working or engaging in daily activities while receiving therapy.
  • Cost and access: Onpattro is a specialty medication. Insurance coverage and patient-assistance programs are often available through the manufacturer and rare-disease support organizations.

The Bottom Line

Onpattro (patisiran) represents a major advancement in the treatment of hereditary transthyretin amyloidosis. By harnessing RNA interference technology, it directly targets the genetic cause of the disease, reducing the buildup of harmful amyloid proteins and improving patients’ quality of life.

For those living with hATTR amyloidosis, Onpattro offers not only relief from symptoms but also hope for slowing disease progression — an achievement once thought impossible.