Rystiggo

Rystiggo is a prescription medicine used to treat generalized myasthenia gravis (gMG) in adults who are anti-acetylcholine receptor (AChR) antibody positive or anti-muscle-specific tyrosine kinase (MuSK) antibody positive. It is given as a subcutaneous infusion (an infusion under the skin) once a week for 6 weeks, in a treatment cycle supervised by a healthcare provider.

Generalized myasthenia gravis is an autoimmune condition, which means the immune system mistakenly attacks the body's own tissue. In gMG, the immune system makes antibodies that attack the connection between nerves and muscles. This disrupts the signals that tell muscles to move, leading to muscle weakness and tiredness that can affect the eyes, face, throat, arms, and legs.

Rystiggo works by blocking a protein called the neonatal Fc receptor (FcRn). Normally, FcRn protects a type of antibody called immunoglobulin G (IgG) from being broken down, which keeps it circulating in the blood. Some of these IgG antibodies are the harmful autoantibodies that drive gMG. By blocking FcRn, Rystiggo lowers the overall level of IgG, including these harmful antibodies, which eases the attack on the nerve-muscle connection and can improve symptoms.

Rystiggo (rozanolixizumab-noli) was approved by the FDA on June 26, 2023. It was the first FDA-approved treatment for gMG that includes adults who are anti-MuSK antibody positive, not only those who are anti-AChR antibody positive. It is manufactured by UCB, Inc. There is currently no generic or biosimilar version of Rystiggo.

Rystiggo was studied in a clinical trial called MycarinG (Study 1), which included 200 adults with gMG who were anti-AChR or anti-MuSK antibody positive. Participants received either Rystiggo or a placebo as a once-weekly subcutaneous infusion for 6 weeks.

Effectiveness was measured using the Myasthenia Gravis Activities of Daily Living (MG-ADL) score, which rates how much gMG affects everyday tasks such as talking, chewing, swallowing, and breathing. By week 6, people treated with Rystiggo improved by an average of 3.4 points, compared with 0.8 points with placebo. They also had greater improvements in muscle strength, measured by the Quantitative Myasthenia Gravis (QMG) score.

Improvements were seen in people who were anti-AChR antibody positive (about 90% of the trial) and anti-MuSK antibody positive (about 10%), though the anti-MuSK group was small.

Rystiggo is given as a subcutaneous infusion (an infusion under the skin) by a healthcare provider using an infusion pump. It is not given by mouth or as an injection you give yourself.

• One treatment cycle is one infusion once a week for 6 weeks in a row.
• The dose is based on your body weight (see Dosage below).
• The infusion is given into the lower right or lower left part of the abdomen, below the navel. The infusion site is changed with each dose.
• The infusion is delivered at a rate of up to 20 mL per hour, so the time it takes depends on your dose and volume.
• Your healthcare provider will monitor you during the infusion and for 15 minutes after it is finished to check for an allergic reaction.
• Rystiggo may be given in an infusion center or a clinic. In some areas, infusions by a nurse at home may be possible.

Your healthcare provider will decide whether you need further treatment cycles based on how you are doing. The safety of starting a new cycle sooner than 63 days after the start of the previous cycle has not been established.

• Avoid receiving live or live-attenuated vaccines during treatment with Rystiggo, because your response to them may be reduced and their safety during treatment is not known.

Before you receive Rystiggo, tell your healthcare provider about all your medical conditions, including if you:

• Have a history of infection or think you have an active infection now
• Have received or are scheduled to receive a vaccine (immunization)
• Are pregnant or plan to become pregnant. Based on animal studies, Rystiggo may harm an unborn baby. Tell your healthcare provider right away if you become pregnant while receiving Rystiggo.
• Are breastfeeding or plan to breastfeed. It is not known whether Rystiggo passes into breast milk. Talk to your healthcare provider about the best way to feed your baby during treatment.
• Are taking any medicines, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

There are no contraindications listed for Rystiggo, which means there is no group of people for whom it must never be used. Your healthcare provider will decide if Rystiggo is right for you based on your health.

There is a pregnancy exposure registry that monitors outcomes in women with myasthenia gravis who are exposed to Rystiggo during pregnancy or breastfeeding. You or your healthcare provider can join by contacting UCBCares at 1-844-599-2273 or emailing [email protected].

Rystiggo (rozanolixizumab-noli) is a type of medicine called a neonatal Fc receptor (FcRn) blocker. FcRn is a protein that protects IgG antibodies from being broken down and keeps them circulating in the blood. In generalized myasthenia gravis, some of these IgG antibodies are harmful autoantibodies (such as anti-AChR and anti-MuSK antibodies) that attack the nerve-muscle connection.

By blocking FcRn, Rystiggo stops IgG antibodies from being protected, so more of them are broken down. This lowers the level of IgG, including the harmful autoantibodies, which reduces the immune system's attack on the nerve-muscle connection and can improve muscle strength and function.

Rystiggo belongs to the drug class called neonatal Fc receptor blockers.

Common side effects

The most common side effects of Rystiggo (reported in at least 10% of people in clinical trials) are:

• Headache
• Infections, including upper respiratory tract infections (such as colds)
• Diarrhea
• Fever
• Hypersensitivity (allergic) reactions
• Nausea

Headache was one of the most frequently reported side effects. In a small number of people, headache was severe, and in rare cases, it led to hospitalization or stopping treatment.

Serious side effects and warnings

Infections. Rystiggo may increase your risk of infection. In clinical trials and postmarketing reports, common infections included upper respiratory tract infections, COVID-19, urinary tract infections, herpes simplex infections, and shingles (herpes zoster). Serious infections, including rare fatal cases of pneumonia, have occurred. Your healthcare provider should check you for infection before you start and during treatment. If you have an active infection, your provider may delay your treatment until it clears up. Tell your healthcare provider if you have any history of infection or if you develop signs or symptoms of an infection, such as:

• Fever
• Chills
• Frequent or painful urination
• Cough
• Runny nose or nasal discharge
• Wheezing
• Shortness of breath
• Tiredness
• Sore throat
• Excess phlegm
• Back pain
• Chest pain

Aseptic meningitis. Rystiggo can cause aseptic meningitis, which is inflammation of the lining around the brain and spinal cord that is not caused by a bacterial infection. Tell your healthcare provider right away if you develop signs or symptoms such as severe headache, stiff neck, drowsiness, fever, sensitivity to light, painful eye movements, nausea, or vomiting.

Hypersensitivity (allergic) reactions. Rystiggo can cause allergic reactions, including angioedema (swelling under the skin) and rash. These can be serious and may lead to hospitalization. Your healthcare provider will monitor you during your infusion and for 15 minutes after it finishes. Tell your healthcare provider right away if you develop:

• A skin rash
• Hives
• Itching
• Swelling around your face, neck, or tongue
• Nausea or vomiting
• Abdominal (stomach area) pain

Vaccinations. Because Rystiggo lowers IgG antibody levels, live and live-attenuated vaccines are not recommended during treatment. Complete any age-appropriate vaccinations according to immunization guidelines before you start a new treatment cycle. Talk to your healthcare provider about which vaccines you may need and when.

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

The dose of Rystiggo for generalized myasthenia gravis (gMG) is based on body weight:

• Less than 50 kg (about 110 lb): 420 mg by subcutaneous infusion once a week for 6 weeks
• 50 kg to less than 100 kg (about 110 to 220 lb): 560 mg by subcutaneous infusion once a week for 6 weeks
• 100 kg and above (about 220 lb or more): 840 mg by subcutaneous infusion once a week for 6 weeks

Further treatment cycles may be given based on your healthcare provider's evaluation. The safety of starting a new cycle sooner than 63 days from the start of the previous cycle has not been established.

What happens if I miss a dose?

If you miss a scheduled Rystiggo infusion, contact your healthcare provider. The dose may be given up to 4 days after the originally scheduled time. After that, the original weekly schedule is resumed until the cycle is complete.

Tell your healthcare provider about all the medicines you take, including prescription medicines, over-the-counter medicines, vitamins, and herbal supplements.

In particular, tell your provider if you take any medicine that binds to the neonatal Fc receptor (FcRn), such as:

• Immunoglobulin products
• Monoclonal antibodies
• Certain antibody derivatives that contain the human Fc part of an IgG antibody

Rystiggo may lower the levels of these medicines in your body and make them less effective. If you need to use one of these medicines long term, your provider may consider stopping Rystiggo and using an alternative therapy.

Rystiggo is not broken down by the liver's cytochrome P450 enzymes, so interactions with medicines handled by those enzymes are unlikely.

This is not a complete list of interactions. See the Rystiggo Prescribing Information for more information.

Your healthcare provider will store Rystiggo vials in the refrigerator at 36°F to 46°F (2°C to 8°C) in the original carton to protect them from light. Do not freeze. Do not shake.

If needed, vials may be kept at room temperature up to 77°F (25°C), in the original carton to protect from light, for a single period of up to 20 days. Once a vial has been kept at room temperature, it should not be returned to the refrigerator. Discard the vial if it is not used within 20 days or if the expiration date has passed, whichever comes first.

Active ingredient: rozanolixizumab-noli (140 mg/mL)

Inactive ingredients: histidine, L-histidine hydrochloride monohydrate, polysorbate 80, proline, and water for injection, USP.

Available vial strengths (each at a concentration of 140 mg/mL):

• 280 mg/2 mL (single-dose vial)
• 420 mg/3 mL (single-dose vial)
• 560 mg/4 mL (single-dose vial)
• 840 mg/6 mL (single-dose vial).