Rystiggo Drug Information

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.

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.

Recommended Dosage

The recommended dosage of RYSTIGGO is based on body weight, as shown below in Table 1. Table 1: Recommended 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.

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.

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.

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. 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.

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 a placebo-controlled study (Study 1) in patients with gMG, 133 patients received RYSTIGGO. 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.

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.

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. 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.

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.

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

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.

Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to RYSTIGGO during pregnancy. Patients or their healthcare providers may contact UCBCares at 1-844-599-CARE or email [email protected], so that information about the exposure of RYSTIGGO during pregnancy and/or breastfeeding can be collected. As a healthcare professional, please ask about becoming a member of the MGBase registry (https://www.mgbase.org).

Risk Summary There are limited data on RYSTIGGO use in pregnant women to inform a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Following administration of rozanolixizumab-noli to pregnant monkeys at doses greater than those used clinically, increases in embryonic death, reduced body weight, and impaired immune function were observed in the absence of maternal toxicity ( see Data ). All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

The background rate of major birth defects and miscarriage in the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is respectively. Data Animal Data Subcutaneous administration of rozanolixizumab-noli (0, 50, or 150 mg/kg) to pregnant monkeys every 3 days throughout pregnancy (gestation day 20 to parturition) resulted in an increase in embryonic death and reduced body weight and impaired immune function in offspring at both doses.

A no-effect dose for adverse developmental effects was not identified; the doses tested in monkeys are 10 and 30 times the maximum recommended human dose of approximately 10 mg/kg, on a mg/kg/week basis.

Pediatric Use Safety and effectiveness in pediatric patients have not been established.