Onpattro

Onpattro is used to treat the polyneuropathy caused by hereditary transthyretin-mediated amyloidosis (hATTR) in adults. It is given by intravenous infusion via a healthcare provider once every 3 weeks.

The APOLLO clinical trial (NCT01960348) reported that 56% of patients assigned to Onpattro showed improvement in their nerve function after 18 months, compared to only 4% receiving a placebo.

• More than 51% had an improved quality of life.

Onpattro (patisiran) gained FDA approval on August 10, 2018.

Onpattro is given by intravenous infusion once every 3 weeks, by a healthcare professional in a doctor's office or infusion center.

Before your infusion:

• At least 60 minutes before the infusion, you will receive a combination of medications commonly used to reduce the risk of infusion-related reactions (IRRs).

Receiving Onpattro:

• Your infusion will take about 80 minutes. Consider bringing a book or some other activity you enjoy to help pass the time.

Infusion options:

• You may be eligible to have your treatment administered at home if covered by your insurance plan. Talk to your doctor to find out if home administration is right for you.

Vitamin A Supplements

Your doctor may have you take vitamin A while you are using Onpattro.

• Take only the amount of vitamin A your doctor has prescribed, especially if you are pregnant.
• An overdose of vitamin A can cause vision problems or other serious side effects.

Alnylam Assist is a patient support program offering patients and their families help with starting Onpattro treatment, understanding insurance coverage, and accessing financial assistance.

• An Alnylam Case Manager will work with you to begin treatment and maintainaccess to Onpattro
• Financial assistance programs may include: Alnylam Assist Patient Assistance Program (PAP) provides Onpattro at no costto eligible patients, primarily the uninsured, who meet specified financial criteria Alnylam Assist Commercial Copay Program covers certain out-of-pocket costs foreligible patients with commercial insurance
• An Alnylam Patient Education Liaison (PEL) can provide education to help youand your family better understand the disease and answer your questions aboutOnpattro. Note: PELs are employees of Alnylam Pharmaceuticals. They are not acting as healthcareproviders and are not part of your healthcare team.

For more information, see Onpattro Prices, Coupons, Copay Cards & Patient Assistance.

Before receiving Onpattro, tell your healthcare provider about all your medical conditions or allergies. Especially tell your doctor if you:

• Have a vitamin A deficiency
• Are pregnant or planning a pregnancy
• Are breastfeeding or planning to breastfeed.

Pregnancy

Onpattro may harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant. If you are pregnant, your name may be listed on a pregnancy registry to track the effects of Onpattro on the baby.

Breastfeeding

It may not be safe to breastfeed while using this medicine. Ask your doctor about any risks.

Common side effects

The most common side effects of Onpattro are:

• Upper respiratory tract infections, such as colds, sinus infections, and nasal congestion
• Infusion-related reactions (with symptoms such as flushing, back pain, nausea, stomach pain, difficulty breathing, and headache).

Serious side effects and warnings

Onpattro can cause the following serious side effects.

Infusion-related reactions

Onpattro is given as a drip into a vein (called an “intravenous infusion”). Reactions to this infusion may happen during treatment with Onpattro. Before each infusion, you will be given medicines that help to lower the chance of infusion-related reactions.

Tell your doctor or nurse right away if you experience any of the following signs of an infusion‑related reaction during treatment:

• Reddening of the face or body (flushing), skin warm
• Body aches or pain, including pain in the back, neck, or joints
• Feeling sick (nausea)
• Stomach pain
• Feeling short of breath, cough, or other breathing problems
• Headache
• Chest discomfort or chest pain
• Rash
• Chills
• Dizziness
• Feeling tired (fatigue)
• Rapid heart rate
• Facial swelling

If you have an infusion-related reaction, your doctor or nurse may slow down or stop your infusion, and you may need to take other medicines. When these reactions stop or get better, your doctor or nurse may decide to start the infusion again.

Low Vitamin A levels

Treatment with Onpattro (patisiran) lowers the amount of vitamin A in your blood. Your doctor will tell you to take a vitamin A supplement every day. You should not take more than the amount of vitamin A recommended by your doctor.

Low vitamin A levels can affect vision. If you have problems with your vision (e.g., night blindness) while taking Onpattro, talk to your doctor. Your doctor may refer you to an eye specialist.

Notes:

This is not a complete list of side effects, and others may occur. Talk to your doctor about side effects that you experience. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Onpattro (patisiran) works by breaking down mutant and wild-type transthyretin (TTR) proteins through RNA interference. TTR is an important protein primarily produced by the liver that carries the thyroid hormone thyroxine and retinol (vitamin A) throughout the body. Onpattro decreases serum levels of TTR protein and protein deposits in tissues, relieving the symptoms of polyneuropathy.

• The APOLLO clinical trial reported improvements in nerve function and quality of life.
• Improvements in symptoms, such as diarrhea, constipation, dizziness, difficulty urinating, and vomiting, were also noted.
• Patients receiving Onpattro maintained a healthier weight.
• An increase in walking speed and decreased levels of anxiety, depression, and pain were also reported.

Onpattro belongs to the drug class called transthyretin-directed small interfering RNA.

Adult Dose of Onpattro for Polyneuropathy of hATTR

The recommended dosage of Onpattro is based on weight.

• <100 kg: 0.3 mg/kg every 3 weeks.
• ≥100 kg: 30 mg every 3 weeks.

Call your doctor for instructions if you miss an appointment for your Onpattro.

Other drugs may interact with Onpattro, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all your current medicines and any medicine you start or stop using.

No formal clinical drug interaction studies have been performed, but Onpattro is not expected to cause drug-drug interactions or to be affected by inhibitors or inducers of cytochrome P450 enzymes.

See the Onpattro Package Insert for more information about drug interactions.

Store in the refrigerator between 2°C and 8°C (36°F and 46°F). Do not freeze. Discard the vial if it has been frozen.

If refrigeration is unavailable, Onpattro can be stored at room temperature up to 25°C (up to 77°F) for up to 14 days.

Once diluted, the solution should be administered immediately after preparation. If not used immediately, store in the infusion bag at room temperature (up to 30°C [86°F]) for up to 16 hours (including infusion time). Do not freeze.

Active: patisiran sodium

Inactive: MC-3, 1,2-dimyristoyl-SN-glycero-3-carboxaminopropylpolyethylene glycol 2000 methyl ether, 1,2-distearoyl-sn-glycero-3-phosphocholine, cholesterol, sodium phosphate, dibasic, heptahydrate, monobasic potassium phosphate, sodium chloride, water.

Available as a lipid complex injection: 10 mg/5 mL (2 mg/mL) in a single-dose vial.

Onpattro (patisiran) is manufactured for Alnylam Pharmaceuticals, Inc., 300 Third Street, Cambridge, MA 02142, by PCI San Diego, Inc., 11040 Roselle Street, San Diego, CA 92121.