Onpattro: 7 things you should know

Medically reviewed by Carmen Pope, BPharm. Last updated on March 27, 2023.

1. How it works

• Onpattro is a brand (trade) name for patisiran which may be used to treat nerve damage caused by a rare inherited condition called transthyretin-mediated amyloidosis.
• Transthyretin (TTR) is a protein made by the liver that helps carry thyroid hormones and vitamin A in the blood. In this condition, TTR misfolds (changes shape), binds together, and forms amyloid fibrils which deposit in the heart, nerves, gastrointestinal tract, kidneys, and other organs and tissues, affecting their function. Transthyretin-mediated amyloidosis may also be called familial amyloid polyneuropathy, or abbreviated as ATTR (hereditary form) or hATTR. Transthyretin levels are increased in people with hATTR.
• Onpattro (patisiran) contains small lipid nanoparticles that contain small interfering RNAs that decrease TTR and TTR deposits in tissues by breaking down mutated or wild-type genetic material that codes for TTR. This mutant/wild-type genetic material is prevalent in people with hATTR. Onpattro aims to stop or reverse the progression of neuropathy associated with hATTR amyloidosis.
• Onpattro may be described as RNA interference therapy, a gene silencer, or a double-stranded, small interfering ribonucleic acid (siRNA). It belongs to the class of medicines known as miscellaneous metabolic agents.

2. Upsides

• May be used to treat polyneuropathy (widespread nerve pain) that occurs as a result of hereditary transthyretin-mediated amyloidosis (hATTR) in adults.
• Given to stop or reverse the progression of neuropathy. Polyneuropathy is often the first sign of hATTR and once a person is symptomatic, the neuropathy will progress, often rapidly, and cause severe disability. Left untreated hATTR amyloidosis with polyneuropathy is fatal.
• Reduces symptoms such as nerve pain, numbness, tingling, abnormal heartbeats, diarrhea, constipation, weakness, and problems with limb movement.
• The sooner treatment is started, the more effect it has.
• The first-of-its-kind treatment and approved in 2018. Since then, other treatments have also been approved for hATTR. Before these treatments, a liver transplant was the only known treatment for hATTR.
• Does not require ongoing monitoring, unlike Tegsedi which is only available only through a restricted distribution program under a Risk Evaluation and Mitigation Strategy (REMS).
• No dosage adjustment is required for renal or hepatic impairment or for seniors aged 65 or older. Onpattro has not been studied in moderate to severe hepatic impairment or severe renal impairment.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Upper respiratory tract infections and infusion-related reactions are the most common side effects reported. Other common side effects include heartburn (dyspepsia), shortness of breath, muscle spasms, joint pain, redness, flushing, bronchitis, dizzy spells, and vertigo (feeling off-balance).
• Must be administered by a health care professional as an intravenous infusion every three weeks.
• Dosing is based on actual body weight. For patients weighing less than 100 kg, the recommended dosage is 0.3 mg/kg once every 3 weeks. For patients weighing 100 kg or more, the recommended dosage is 30 mg once every 3 weeks.
• Infusion-related reactions (IRRs) are common in patients treated with Onpattro, affecting about 19% of patients. 79% experienced the first IRR within the first 2 infusions. The frequency of IRRs decreased over time. IRRs led to infusion interruption in 5% of patients. IRRs resulted in permanent discontinuation of Onpattro in less than 1% of patients. Symptoms include flushing, back pain, nausea, abdominal pain, chest pain, dyspnea, and headache; rarely, hypotension and syncope (fainting) have been reported during an Onpattro infusion.
• Premedication is required by all patients at least 60 minutes before an Onpattro administration to reduce the risk of infusion-related reactions. Recommended premedications include an intravenous corticosteroid (such as dexamethasone 10 mg), oral acetaminophen (500 mg), an intravenous H1 blocker (such as diphenhydramine 50 mg), and an intravenous H2 blocker (such as ranitidine 50 mg, or equivalent). If IV premedications are not available or tolerated oral equivalents may be given. Some patients may require additional or higher doses of one or more of the premedications to reduce the risk of IRRs.
• Should be administered every 3 weeks. If a dose is missed and the missed dose 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.
• Onpattro treatment causes a decrease in serum vitamin A levels, and supplementation at the recommended daily allowance of vitamin A is advised for patients taking Onpattro. Do not recommend higher dosages to try and achieve normal serum vitamin A levels during treatment, because serum vitamin A levels do not reflect the total vitamin A in the body. Refer patients to an ophthalmologist if they develop eye symptoms suggestive of vitamin A deficiency, such as night blindness.
• Expensive, around $30,000 every three weeks.
• There is limited data about the formation of anti-drug antibodies with Onpattro.
• There is not enough data to make a definite recommendation about the use or avoidance of Onpattro during pregnancy. Vitamin A is essential for normal fetal development but excessive levels of vitamin A are associated with fetal toxicity. Advise women not to become pregnant while taking Onpattro and to use adequate contraception if they are of childbearing age. If they inadvertently do become pregnant, then encourage them to enroll in the pregnancy exposure registry by calling 1-877-256-9526 or by contacting alnylampregnancyprogram@iqvia.com. There is no information about the effects of Onpattro during breastfeeding.
• The safety and effectiveness of Onpattro in children are unknown.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

Onpattro (patisiran) contains small lipid nanoparticles that contain small interfering RNAs that break down deposits of transthyretin - a protein that is increased by a rare condition called hereditary transthyretin-mediated amyloidosis (hATTR). Onpattro is infused by a healthcare provider every 3 weeks and is effective at stopping or reversing the progression of nerve damage associated with hATTR. Infusion site reactions and upper respiratory tract infections are the most common side effects reported.

5. Tips

• Administered by an IV infusion over approximately 80 minutes, every 3 weeks by a healthcare provider. Doses are based on your weight. You will probably receive this medicine at an infusion center, but may be eligible to receive it at home. Ask your doctor about this option.
• At least one hour before your Onpattro infusion, you will be pre-medicated with a corticosteroid, acetaminophen, and antihistamines to help reduce possible infusion reactions. These reactions most commonly include flushing, back pain, nausea, stomach pain, chest pain, shortness of breath, and headache. Tell your healthcare provider if you experience any of these. Side effects due to infusion reactions tend to lessen over time.
• Keep your scheduled appointments with your healthcare provider to ensure you receive your infusion of Onpattro every 3 weeks. If you miss a dose, reschedule your appointment to get Onpattro as soon as possible.
• Your doctor will talk to you about supplementation with vitamin A while you are taking Onpattro because Onpattro decreases vitamin A in the body. Do not take more than the recommended daily allowance of vitamin A. Make an appointment with an opthalmologist if you experience symptoms of vitamin A deficiency such as night blindness.
• It is unknown how Onpattro affects pregnant women or their developing fetuses. Ensure you use adequate contraception if you are a woman of childbearing age. If you inadvertently do become pregnant, then enroll in the pregnancy exposure registry by calling 1-877-256-9526 or by contacting alnylampregnancyprogram@iqvia.com. There is no information about the effects of Onpattro on breastfeeding infants.

6. Response and effectiveness

• An overall difference of -34 was reported in the primary endpoint of change in baseline after 18 months of the mNIS (modified Neuropathy Impairment Score +7 [mNIS+7]) in an RCT where 148 people were assigned to receive Onpattro 0.3 mg/kg or placebo (77 people).
• Secondary endpoints included the Norfolk Quality of Life-Diabetic Neuropathy (QoL-DN) total score where a difference of -21.1 was reported. Changes in baseline for modified body mass index and gait speed favored Onpattro.

7. Interactions

Medicines that interact with Onpattro may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with Onpattro. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

No formal clinical drug interaction studies have been performed with Onpattro and the product information does not list any interactions. Onpattro does not inhibit or induce any cytochrome P450 enzymes or transporters at clinically relevant plasma concentrations and is not a substrate of cytochrome P450 enzymes.

Onpattro is not expected to cause drug-drug interactions or to be affected by inhibitors or inducers of cytochrome P450 enzymes.

Always refer to the prescribing information for Onpattro for any interaction updates.

References

• Onpattro (patisiran). Updated 01/2023. Alnylam Pharmaceuticals, Inc. https://www.drugs.com/pro/onpattro.html

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use Onpattro only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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