ONPATTRO (patisiran) is a significant advancement in treating the polyneuropathy associated with a rare, debilitating condition. However, its high price tag is a major consideration for patients and healthcare systems. Understanding the full cost, how it's calculated, and what support is available is crucial.
What is ONPATTRO (patisiran)?
ONPATTRO is an FDA-approved prescription medication used to treat polyneuropathy (damage to multiple nerves) in adults with hereditary transthyretin-mediated amyloidosis (hATTR) [1.4.2, 1.4.5]. This is a rare, inherited disease where an abnormal protein called transthyretin (TTR) builds up in the body, forming amyloid deposits [1.4.3]. These deposits can accumulate in nerves, the heart, and other organs, causing progressive and severe symptoms [1.5.3]. Approved in 2018, ONPATTRO was the first RNA interference (RNAi) therapy to receive FDA approval [1.4.6].
How ONPATTRO Works: The Science of Gene Silencing
ONPATTRO functions through a groundbreaking mechanism called RNA interference (RNAi), often referred to as gene silencing [1.5.3, 1.5.5]. The drug contains small interfering RNA (siRNA) molecules that are delivered to the liver, the primary source of TTR protein production [1.5.2, 1.5.4].
Inside the liver cells, the siRNA specifically targets and causes the breakdown of the messenger RNA (mRNA) that carries the instructions for making both the mutated and normal TTR protein [1.5.1]. By interrupting this process, ONPATTRO significantly reduces the amount of TTR protein in the blood, which in turn helps to reduce the buildup of harmful amyloid deposits in the body's tissues [1.5.4]. Clinical studies have shown it can reduce serum TTR levels by about 80% [1.4.4, 1.4.9].
Breakdown of the Annual Cost of ONPATTRO
The cost of ONPATTRO is substantial and can vary based on several factors.
- List Price: The initial list price set by the manufacturer, Alnylam, is approximately $450,000 per patient per year [1.2.2].
- Net Price: After rebates and discounts, particularly through government programs like 340B, the average net price is estimated to be around $345,000 per year [1.2.2, 1.2.3].
- Dosing and Vial Cost: The recommended dosage is 0.3 mg per kg of body weight, administered via intravenous (IV) infusion once every three weeks [1.2.1]. For patients weighing 100 kg (220 lbs) or more, the maximum recommended dose is 30 mg per infusion [1.4.4]. The medication comes in 10 mg vials, each costing around $13,022 [1.2.1]. Depending on a patient's weight, an annual course of treatment can range from $451,430 to $677,145 based on whether two or three vials are needed per infusion [1.2.1].
Financial Assistance and Support Programs
Recognizing the high cost, the manufacturer offers support through Alnylam Assist®. This program provides several services to help patients access treatment [1.3.4, 1.3.5].
- Patient Assistance Program (PAP): This program can provide ONPATTRO at no cost to eligible patients, primarily those who are uninsured or functionally uninsured [1.3.2, 1.3.5].
- Commercial Copay Program: For eligible patients with commercial insurance, this program helps cover out-of-pocket costs [1.3.1, 1.3.7].
- Other Services: Alnylam Assist also helps with navigating insurance verification, prior authorizations, and provides access to case managers who can guide patients through the process [1.3.4, 1.3.6].
Comparison of hATTR Amyloidosis Treatments
ONPATTRO is not the only option for treating hATTR amyloidosis. Other medications work through different mechanisms and have different administration schedules and costs.
| Feature | ONPATTRO (patisiran) | Amvuttra (vutrisiran) | Tegsedi (inotersen) | Vyndamax (tafamidis) |
|---|---|---|---|---|
| Mechanism | RNA interference (siRNA) [1.5.1] | RNA interference (siRNA) [1.6.1] | Antisense Oligonucleotide [1.6.7] | TTR Stabilizer [1.6.7] |
| Administration | IV Infusion [1.4.2] | Subcutaneous Injection [1.6.2] | Subcutaneous Injection [1.6.3] | Oral Capsule [1.6.9] |
| Dosing | Once every 3 weeks [1.4.9] | Once every 3 months [1.6.2] | Once weekly [1.6.3] | Once daily [1.6.1] |
| Primary Indication | Polyneuropathy [1.4.2] | Polyneuropathy [1.6.1] | Polyneuropathy [1.6.4] | Cardiomyopathy [1.6.1] |
| Key Risks | Infusion-related reactions, low Vitamin A levels [1.4.2, 1.4.4] | Joint pain, shortness of breath [1.2.5] | Thrombocytopenia, glomerulonephritis (Requires REMS program) [1.4.2] | Diarrhea, urinary tract infection [1.6.9] |
Common Side Effects and Considerations
The most common side effects reported with ONPATTRO are upper respiratory infections and infusion-related reactions (IRRs) [1.4.2, 1.4.8]. To minimize the risk of IRRs, patients receive premedication—including a corticosteroid, acetaminophen, and two antihistamines—about an hour before the infusion [1.4.2]. Additionally, because ONPATTRO lowers TTR protein which transports Vitamin A, treatment leads to a decrease in serum Vitamin A levels. Patients are advised to take a daily Vitamin A supplement as prescribed by their doctor [1.4.4, 1.4.9].
Conclusion
ONPATTRO is a transformative therapy for adults with polyneuropathy caused by hATTR amyloidosis, offering a way to slow or halt disease progression by targeting its genetic root. While its annual cost is very high, the net price is often lower due to various discounts. Furthermore, programs like Alnylam Assist exist to provide significant financial support, potentially making the treatment accessible at little to no cost for eligible individuals. The decision to use ONPATTRO versus an alternative therapy depends on a comprehensive evaluation of the patient's specific symptoms, lifestyle, and overall health profile in consultation with a physician knowledgeable in amyloidosis.
Learn more about financial support options at Alnylam Assist.
