General Information

Onpattro (patisiran) contains a transthyretin-directed small interfering RNA. Onpattro utilizes a novel approach to target and reduce production of the TTR protein in the liver via the RNAi pathway. Reducing the TTR protein leads to a reduction in the amyloid deposits that accumulate in tissues.

Onpattro is specifically indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults. 

Onpattro is supplied as a solution for intravenous infusion. Infuse over approximately 80 minutes. Pre-medicate with a corticosteroid, acetaminophen, and antihistamines to reduce the risk of infusion related reactions. Dosing is based on body weight:

• For patients weighing less than 100 kg, the recommended dosage is 0.3 mg/kg every 3 weeks by intravenous infusion.
• For patients weighing 100 kg or more, the recommended dosage is 30 mg once every 3 weeks.

If a dose is missed, administer Onpattro as soon as possible. If Onpattro is administered within 3 days of the missed dose, continue dosing according to the patient’s original schedule. If Onpattro is administered more than 3 days after the missed dose, continue dosing every 3 weeks thereafter. 

Mechanism of Action

Onpattro (patisiran) is a double-stranded siRNA that causes degradation of mutant and wild-type TTR mRNA through RNA interference, which results in a reduction of serum TTR protein and TTR protein deposits in tissues. 

Side Effects

Adverse effects associated with the use of Onpattro may include, but are not limited to, the following:

• upper respiratory tract infections
• infusion-related reactions

Clinical Trial Results

The FDA approval of Onpattro was based on the randomized, double-blind, placebo-controlled, global Phase III APOLLO study. The study enrolled 225 subjects who received intravenous Onpattro (0.3 mg per kg of body weight) or placebo once every 3 weeks for 18 months. The primary endpoint of the APOLLO study was the modified Neuropathy Impairment Score +7 (mNIS+7), which assesses motor strength, reflexes, sensation, nerve conduction and postural blood pressure. Patients treated with Onpattro had a mean 6.0-point decrease (improvement) in mNIS+7 score from baseline compared to a mean 28.0-point increase (worsening) for patients in the placebo group, resulting in a mean 34.0-point difference relative to placebo, after 18 months of treatment. Nearly all Onpattro-treated patients experienced a treatment benefit relative to placebo, and 56% of Onpattro-treated patients at 18 months of treatment experienced reversal of neuropathy impairment (as assessed by mNIS+7 score) relative to their own baseline, compared to four percent of patients who received placebo.