Rystiggo (rozanolixizumab-noli) for myasthenia gravis

Last updated Jan. 25, 2024, by Marta Figueiredo, PhD
Fact-checked by Joana Carvalho, PhD

What is Rystiggo for myasthenia gravis?

Rystiggo (rozanolixizumab-noli) is an injection therapy approved for adults with generalized myasthenia gravis (gMG) who have antibodies against the acetylcholine receptor (AChR) or muscle-specific tyrosine kinase (MuSK) — the two most common disease-causing antibodies.

Administered via under-the-skin, or subcutaneous, injections, the therapy was developed by UCB, which also is testing it for other indications. It works to ease symptoms of the chronic autoimmune disorder, which causes muscle weakness in different parts of the body.

Therapy snapshot

How does Rystiggo work?

Myasthenia gravis (MG) is an autoimmune disease in which a person’s immune system wrongly produces self-reactive antibodies against proteins involved in the communication between nerves and muscles. This autoimmune attack impairs nerve-muscle communication, resulting in the typical MG symptoms of muscle weakness and fatigue.

The most common target of MG-driving antibodies is the AChR protein, which triggers muscle contraction upon binding to a signaling molecule called acetylcholine.

Some patients are instead positive for antibodies targeting another protein involved in nerve-muscle communication called MuSK. A smaller percentage of patients lack any of these antibodies.

Formerly known as UCB7665, Rystiggo is an antibody-based therapy that works by binding to the neonatal Fc receptor (FcRn) — a protein that normally prevents the destruction of antibodies circulating in the bloodstream, including the self-reactive ones that drive MG.

By preventing MG-driving antibodies from interacting with FcRn, Rystiggo is expected to speed the pace at which these harmful antibodies are destroyed, lowering their levels in the bloodstream and ultimately helping to ease MG symptoms.

Who can take Rystiggo?

Rystiggo was approved by the U.S. Food and Drug Administration in June 2023 to treat adults with gMG who were positive for antibodies against either AChR or MuSK proteins. This decision made Rystiggo the first treatment available for the two most common subtypes of gMG.

In Europe, Rystiggo has also been approved as an add-on to standard therapy for the treatment of adults with gMG who are positive for antibodies against either AChR or MuSK proteins in January 2024.

Who should not take Rystiggo?

There are no known contraindications for the use of Rystiggo. However, the therapy is not recommended for patients with an active infection, and it should be delayed until that infection is resolved.

Rystiggo also has been associated with hypersensitivity reactions, including rash and swelling of the deeper layers of the skin. The therapy may need to be discontinued in patients who have such reactions and appropriate treatment begun.

How is Rystiggo administered?

Rystiggo is available as single-dose vials containing 2 mL of a colorless to pale brownish-yellow solution with 280 mg of the medication. It is administered via a subcutaneous infusion pump at a maximum rate of 20 mL per hour, once a week, for six weeks.

Dosing of Rystiggo varies according to a patient’s body weight:

• For gMG patients weighing less than 50 kg (about 110 pounds), the recommended dose is 420 mg (3 mL of the solution).
• For those weighing 50 kg to less than 100 kg (about 220 pounds), the recommended dose is 560 mg (4 mL of the solution).
• For those weighing 100 kg or more, the recommended dose is 840 mg (6 mL of the solution).

Additional six-week treatment cycles should be given based on a patient’s clinical response, but intervals of less than 63 days between cycles have not been evaluated in terms of safety.

If a planned dose is missed, Rystiggo can be given up to four days after the scheduled time. Thereafter, patients should resume the original dosing schedule until completion of the treatment cycle.

Rystiggo should only be prepared and administered by a healthcare provider.

Rystiggo in clinical trials

Rystiggo’s approvals were mainly supported by data from a Phase 3 clinical trial called MycarinG (NCT03971422).

MycarinG trial

The global MycarinG study enrolled 200 adults with gMG — 179 (89.5%) with anti-AChR antibodies and 21 (10.5%) with anti-MuSK antibodies — at 81 sites across North America, Europe, and Asia.

Participants were randomly assigned to receive either Rystiggo (at a dose of 7 or 10 mg/kg) or a placebo, given as weekly subcutaneous infusions for six weeks. This was followed by an eight-week observation period to determine treatment safety.

The trial’s main goal was to assess changes in the score of the MG Activities of Daily Living (MG-ADL) scale — a survey filled out by patients that assesses the severity of symptoms and how they affect daily activities — from the study’s start (baseline) to day 43 (about six weeks). Total scores in this scale range from 0 to 24, with higher scores indicating greater disability.

Top-line results showed that either dose of Rystiggo resulted in significantly greater reductions in MG-ADL scores compared with a placebo (a mean drop of 3.4 points vs. less than 1 point).

A significantly greater proportion of patients treated with Rystiggo also attained clinically meaningful MG-ADL score reductions, defined as two-point or greater drops, and were considered responders (about 70% with either dose vs. 31% with placebo).

Moreover, Rystiggo-treated patients showed significantly greater score reductions in two other measures of disease severity — the Quantitative MG (QMG) and the MG Composite (MGC) scales — and patient-reported outcome scales relative to those on a placebo. QMG is a clinician-rated measure of symptom severity, while MGC is a composite measure that considers both patient reports and clinical assessments.

Score improvements across all measures were seen as early as day eight and reached a peak around week six, returning to initial levels at day 99 — about two months after completing treatment.

Subgroup analyses showed that patients with anti-MuSK antibodies also experienced statistically significant and clinically meaningful improvements with Rystiggo across all measures.

In fact, both doses of the therapy generally resulted in greater mean score reductions in the MG-ADL, QMG, and MGC scales in this subgroup of patients than in those with anti-AChR antibodies.

Also, a greater proportion of Rystiggo-treated patients were considered treatment responders across all three measures compared with those on a placebo, regardless of antibody type.

Additional subgroup analyses indicated that either dose of the therapy was associated with clinically meaningful MG-ADL score reductions regardless of disease duration, disease severity, and number of previous lines of treatment.

Extension studies

After completing MycarinG, participants had the option to enroll in one of two sequential, open-label extension studies: MG0004 (NCT04124965) and MG0007 (NCT04650854).

In MG0004, participants were given weekly Rystiggo infusions for up to a year. Those completing at least six treatment visits could move on to the ongoing MG0007 extension study, in which participants are receiving additional six-week Rystiggo treatment cycles for up to 2.5 years. The timing between treatment cycles is tailored to a patient’s symptoms.

Pooled data from MycarinG, MG0007, and the first treatment cycle in MG0004 showed  Rystiggo led to consistent benefits across treatment cycles, as assessed with changes in MG-ADL, QMG, and MGC scores. In addition, more than half of the patients had treatment-free periods of about one to three months before starting any next treatment cycle.

Ongoing trials

UCB has launched an international open-label Phase 3 trial (NCT05681715) to evaluate whether gMG adults can successfully self-administer Rystiggo at home after appropriate training. Two different methods will be tested. The study, started in April 2023, aims to recruit up to 30 patients who will receive predefined weekly doses of the therapy for about four months. The study is expected to be complete by June 2024.

Common side effects of Rystiggo

The most common side effects of Rystiggo include:

• headache
• infections
• diarrhea
• fever
• allergic reactions
• nausea.

Infections

Because Rystiggo works by decreasing the levels of antibodies, including those that help the body fight off pathogens, the therapy can increase a person’s risk of developing infections. It may also reduce the body’s ability to fight active or latent infections.

Treatment with Rystiggo should be delayed in patients with an active infection until that infection is resolved, and patients should be monitored for clinical signs or symptoms of infection while receiving the therapy. If a serious injection develops, patients should be given appropriate treatment and Rystiggo interruption should be considered until that infection has resolved.

Vaccines containing a live or a live-attenuated virus should not be given to patients on Rystiggo due to potential reduced vaccine efficacy. It’s recommended patients are vaccinated according to current guidelines before starting a new treatment cycle of the medication.

Aseptic meningitis

Serious cases of aseptic meningitis — a group of inflammatory conditions affecting the brain and spinal cord that are not caused by the presence of bacteria — have been reported in patients on Rystiggo.

Patients should be monitored for symptoms of aseptic meningitis, including fever, severe headache, neck pain or stiffness, increased eye sensitivity to bright light, nausea, and vomiting. If these occur, physicians should conduct diagnostic testing and start appropriate treatment.

Allergic reactions

Treatment with Rystiggo may cause allergic reactions, including rash and swelling. Patients should be monitored for potential signs or symptoms of allergic reactions during infusion and up to 15 minutes thereafter. If an allergic reaction occurs, patients should seek medical attention and healthcare professionals should begin appropriate measures depending on the reaction’s type and severity.

Use in pregnancy and breastfeeding

The use of Rystiggo in people who are pregnant or breastfeeding has not been rigorously studied. However, studies done in pregnant monkeys have suggested the therapy may cause harm to the developing fetus.

The therapy’s presence in human breast milk and its potential effects on a breastfed infant, or on milk production in nursing patients, remain largely unclear.

Patients who are pregnant or nursing, or plan to become pregnant or breastfeed, should discuss this topic with their healthcare team and carefully weigh the potential benefits and risks of using Rystiggo in these circumstances.

Myasthenia Gravis News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.