RYSTIGGO

Rozanolixizumab-noli, a neonatal Fc receptor blocker, is a recombinant, humanized IgG4P monoclonal antibody, expressed in a genetically engineered Chinese hamster ovary DG44 cell line. Rozanolixizumab-noli has an approximate molecular weight of 148 kDa. RYSTIGGO 140 mg/mL (2 mL, 3 mL, 4 mL, and 6 mL vials) RYSTIGGO (rozanolixizumab-noli) injection is a sterile, preservative-free, clear to slightly opalescent, colorless to pale brownish yellow solution for subcutaneous infusion. Each single-dose vial contains 280 mg, 420 mg, 560 mg, or 840 mg of rozanolixizumab-noli at a concentration of 140 mg/mL with a pH of 5.6. Each mL also contains histidine (1.05 mg), L-histidine hydrochloride monohydrate (4.87 mg), polysorbate 80 (0.30 mg), proline (28.78 mg), and water for injection, USP.

RYSTIGGO is indicated for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody positive. RYSTIGGO (rozanolixizumab-noli) is a neonatal Fc receptor blocker indicated for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody positive. ( 1 )

Evaluate the need to administer age-appropriate vaccines according to immunization guidelines before initiation of a new treatment cycle with RYSTIGGO. ( 2.1 ) For subcutaneous infusion only. ( 2.2 ) The recommended dosage is administered as a subcutaneous infusion once weekly for 6 weeks. ( 2.2 ) Body Weight of Patient Dose Volume to be Infused Less than 50 kg 420 mg 3 mL 50 kg to less than 100 kg 560 mg 4 mL 100 kg and above 840 mg 6 mL Administer subsequent treatment cycles based on clinical evaluation; the safety of initiating subsequent cycles sooner than 63 days from the start of the previous treatment cycle has not been established. ( 2.2 ) 2.1 Recommended Vaccination Because RYSTIGGO causes transient reduction in IgG levels, immunization with live-attenuated or live vaccines is not recommended during treatment with RYSTIGGO. Evaluate the need to administer age-appropriate immunizations according to immunization guidelines before initiation of a new treatment cycle with RYSTIGGO [see Dosage and Administration (2.2) and Warnings and Precautions (5.1) ] . 2.2 Recommended Dosage The recommended dosage of RYSTIGGO is based on body weight, as shown below in Table 1. Table 1: Recommended Dose Based on Body Weight Body Weight of Patient Dose Volume to be Infused Less than 50 kg 420 mg 3 mL 50 kg to less than 100 kg 560 mg 4 mL 100 kg and above 840 mg 6 mL Administer the recommended dosage as a subcutaneous infusion using an infusion pump at a rate of up to 20 mL/hour once weekly for 6 weeks. For detailed preparation and administration instructions, see Preparation and Administration Instructions (2.3) . Administer subsequent treatment cycles based on clinical evaluation. The safety of initiating subsequent cycles sooner than 63 days from the start of the previous treatment cycle has not been established. If a scheduled dose is missed, RYSTIGGO may be administered up to 4 days after the scheduled time point. Thereafter, resume the original dosing schedule until the treatment cycle is completed. 2.3 Preparation and Administration Instructions RYSTIGGO should only be prepared and infused by a healthcare provider. RYSTIGGO is for subcutaneous administration only using an infusion pump. Refer to the infusion pump manufacturer's instructions for full preparation and administration information. It is recommended to use pumps where the administered volume can be pre-set as each vial contains excess volume for priming of the infusion line. The following criteria are recommended for administration of RYSTIGGO: Syringe pump occlusion alarm limits should be at the maximum setting Administration tubing length should be 61 cm or shorter Infusion set with a needle of 26 gauge or larger should be used. Read the instructions below before preparing and administering RYSTIGGO solution. Use aseptic technique when preparing and administering RYSTIGGO. Prior to use, allow vials to reach room temperature for approximately 30 minutes. Do not use heating devices. Keep the vial in the original carton to protect from light until ready to use. Do not shake. Vials may be stored at room temperature up to 77°F (25°C) for a single period of up to 20 days in the original carton [see How Supplied/Storage and Handling (16.2) ]. Infuse RYSTIGGO within 4 hours of puncturing the vial. RYSTIGGO should be administered immediately after priming the infusion set. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The solution should be colorless to pale brownish-yellow, clear to slightly opalescent. Do not use the vial if the liquid looks cloudy, contains foreign particles, or has changed color. Use transfer needles to fill the syringe. Remove the needle from the syringe and attach the infusion set to the syringe. Follow the device manufacturer's instructions to prepare the pump and prime the tubing. Choose an infusion site in the lower right or lower left part of the abdomen below the navel and clean with an alcohol wipe. Do not infuse where the skin is tender, bruised, red, or hard. Avoid infusing into tattoos, scars, or stretch marks. Rotate infusion sites for subsequent administrations. Insert the infusion set needle into the infusion site and secure the needle to the skin with sterile gauze and tape or a transparent dressing. Infuse RYSTIGGO at a constant flow rate up to 20 mL/hour. Monitor patients during administration and for 15 minutes after completion for clinical signs and symptoms of hypersensitivity reactions. If a hypersensitivity reaction occurs during administration, discontinue administration of RYSTIGGO and institute appropriate supportive measures [see Warnings and Precautions (5.3) ]. When the infusion is complete, do not flush the infusion line as the volume of infusion has been adjusted taking into account the losses in the line. Each RYSTIGGO vial is for one-time use only. RYSTIGGO does not contain preservatives. Discard any remaining solution.

None. None. ( 4 )

The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling: Infections [see Warnings and Precautions (5.1) ] Aseptic Meningitis [see Warnings and Precautions (5.2) ] Hypersensitivity Reactions [see Warnings and Precautions (5.3) ] The most common adverse reactions (≥10%) in patients with gMG are headache, infections, diarrhea, pyrexia, hypersensitivity reactions, and nausea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact UCB, Inc. at 1-844-599-2273 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In clinical studies, the safety of RYSTIGGO has been evaluated in 196 patients who received at least one dose of RYSTIGGO, including 88 patients exposed to at least 5 treatment cycles and 9 patients exposed to at least 10 treatment cycles. In a placebo-controlled study (Study 1) in patients with gMG, 133 patients received RYSTIGGO [see Clinical Studies (14) ] . Of these 133 patients, approximately 56% were female, 68% were White, 12% were Asian, and 6% were of Hispanic or Latino ethnicity. The mean age at study entry was 52.5 years (range 19 to 89 years). Patients treated with RYSTIGGO received 1 treatment cycle in Study 1. In an extension study, the minimum time for initiating subsequent treatment cycles, specified by study protocol, was 63 days from the start of the previous treatment cycle. Patients treated with RYSTIGGO on average initiated 4 cycles in one year (range 1 to 7 cycles). The median time between start of treatment cycles was 98 days for patients treated with RYSTIGGO who initiated 4 cycles. Adverse reactions reported in at least 5% of patients treated with RYSTIGGO and more frequently than placebo are summarized in Table 2. The most common adverse reactions (reported in at least 10% of patients treated with RYSTIGGO) were headache, infections, diarrhea, pyrexia, hypersensitivity reactions, and nausea. Table 2: Adverse Reactions in at least 5% of Patients Treated with RYSTIGGO and More Frequently than in Patients who Received Placebo in Study 1 (Safety Population) Adverse Reaction RYSTIGGO (N = 133) % Placebo (N = 67) % Headache 44 19 Any infection 23 19 Upper respiratory tract infection 8 6 Diarrhea 20 13 Pyrexia 17 2 Hypersensitivity reactions 11 5 Nausea 10 8 Administration site reactions 8 3 Abdominal pain 8 6 Arthralgia 7 3 Infections In Study 1 and the extension studies, out of 196 patients treated with RYSTIGGO, 94 (48%) patients reported infections. Common infections (at least 5% frequency) were upper respiratory tract infections (17%), COVID-19 (14%), urinary tract infections (9%), and herpes simplex (6%). Serious infections were reported in 4% of patients treated with RYSTIGGO. Three fatal cases of pneumonia were identified caused by COVID-19 infection in two patients and an unknown pathogen in one patient. Six cases of infections led to discontinuation of RYSTIGGO [see Warnings and Precautions (5.1) ]. Aseptic Meningitis In clinical trials, one patient with gMG and two patients with another neurological disease experienced a serious adverse reaction of drug-induced aseptic meningitis, which led to hospitalization and discontinuation of RYSTIGGO [see Warnings and Precautions (5.2) ]. Hypersensitivity Reactions and Administration Site Reactions In clinical trials, hypersensitivity reactions occurred within 1 day to 2 weeks of administration. One patient discontinued RYSTIGGO due to a hypersensitivity reaction [see Warnings and Precautions (5.3) ]. Local reactions at the administration site occurred within 1 to 3 days after the most recent RYSTIGGO infusion. Headache In Study 1, seven (5.3%) cases of severe headache were reported in patients treated with RYSTIGGO. None of the patients who received placebo reported severe headache. One patient was hospitalized due to severe headache and one patient discontinued treatment due to severe headache associated with fever, photophobia, phonophobia, nausea, and vertigo. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of RYSTIGGO. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Infections: herpes zoster

Closely monitor for reduced effectiveness of medications that bind to the human neonatal Fc receptor. When concomitant long-term use of such medications is essential for patient care, consider discontinuing RYSTIGGO and using alternate therapies. ( 7.1 ) 7.1 Effect of RYSTIGGO on Other Drugs Concomitant use of RYSTIGGO with medications that bind to the human neonatal Fc receptor (FcRn) (e.g., immunoglobulin products, monoclonal antibodies, or antibody derivatives containing the human Fc domain of the IgG subclass) may lower systemic exposures and reduce effectiveness of such medications. Closely monitor for reduced effectiveness of medications that bind to the human neonatal Fc receptor. When concomitant long-term use of such medications is essential for patient care, consider discontinuing RYSTIGGO and using alternative therapies.

16.2 Storage and Handling Store vials refrigerated at 36°F to 46°F (2°C to 8°C) in the original carton to protect from light until the time of use. Do not freeze. Do not shake. If needed, vials may be stored at room temperature up to 77°F (25°C) for a single period of up to 20 days in the original carton to protect the vial from light. Once a vial has been stored at room temperature, it should not be returned to the refrigerator. The discard date is 20 days after removal of the vial from the refrigerator. Write the discard date in the space provided on the carton. Discard the vial if not used within 20 days or if the expiration date has passed, whichever occurs first.