Repeated treatment cycles ease gMG symptoms across long-term study
Rystiggo was generally well tolerated during repeated use over about 2 years
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- Rystiggo consistently eased gMG symptoms across repeated cycles over about two years.
- It lowered gMG-driving antibodies, while some patients reduced corticosteroid use.
- Rystiggo was generally well tolerated, and most adverse events were mild or moderate.
Repeated cycles of Rystiggo (rozanolixizumab-noli) were generally well tolerated and consistently eased symptoms over a median study duration of about two years among people with generalized myasthenia gravis (gMG).
That’s according to a final analysis of pooled data from the global Phase 3 MycarinG clinical trial (NCT03971422) and two open-label extension studies that followed it: the up-to-one-year MG0004 trial (NCT04124965) and the up-to-three-year MG0007 trial (NCT04650854).
“These data suggest that repeated [Rystiggo] cycles can be used for long-term treatment in patients with gMG,” the researchers wrote.
Study examines long-term use of repeated Rystiggo cycles
The findings, previously presented at a scientific conference, were published in Therapeutic Advances in Neurological Disorders, in a study titled “Long-term use of rozanolixizumab in generalised myasthenia gravis: final pooled analysis of the phase III MycarinG study and two open-label extensions.”
In gMG, self-targeting antibodies interfere with proteins needed for communication between nerves and muscles. This leads to muscle weakness that fluctuates and worsens with activity. The two most common targets of the antibodies that drive gMG are the acetylcholine receptor (AChR) and muscle-specific tyrosine kinase (MuSK) proteins.
Developed by UCB, Rystiggo is designed to block a receptor protein called FcRn, which normally protects circulating immunoglobulin G (IgG) antibodies from being broken down. By blocking FcRn, Rystiggo lowers IgG levels, including the harmful antibodies that drive MG symptoms. Treatment involves once-weekly subcutaneous, or under-the-skin, infusions for six weeks, with additional cycles given as needed to control symptoms.
The therapy is approved in the U.S. for adults with gMG who test positive for anti-AChR or anti-MuSK antibodies and in the European Union as an add-on to standard therapy for the same patient population. Those approvals were based largely on results from MycarinG.
In MycarinG, one six-week Rystiggo cycle was more effective than a placebo at reducing the effects of gMG on participants’ daily activities, as measured by the MG Activities of Daily Living (MG-ADL) scale.
After completing MycarinG, eligible participants could enroll in MG0004 and later MG0007, or enter MG0007 directly. In MG0004, participants received Rystiggo once weekly for up to 52 weeks. In MG0007, they received an initial six-week cycle, followed by additional cycles when their symptoms worsened, based on the investigator’s judgment. Earlier pooled findings indicated that the therapy’s safety and efficacy were consistent across one to six cycles.
The final safety analysis included 188 patients who received at least one treatment cycle, with some receiving as many as 18 cycles. Their median total time in the studies was 728.5 days, or about two years.
The separate efficacy analysis included 129 participants who received at least two symptom-driven cycles, meaning additional cycles given after their symptoms worsened. Efficacy results were reported across as many as 13 cycles.
Symptom improvements remained consistent across treatment cycles
Across repeated cycles, patients showed consistent improvements in daily functioning. MG-ADL scores began to decrease, indicating improvement, by day eight and generally reached their greatest reduction between days 29 and 43. From the start of each cycle through day 43, mean score reductions across cycles one through 13 ranged from 3.2 to six points, exceeding the two-point threshold considered clinically meaningful.
Similar improvement patterns were seen on two other validated measures of gMG severity, the MG Composite (MGC) and the Quantitative MG (QMG) scales. Patients also reported improvements in muscle weakness that worsened with activity, physical fatigue, and bulbar muscle weakness, which can affect speaking and swallowing.
Improvements were also observed in both antibody groups. Across cycles one through 13, mean MG-ADL score reductions by day 43 ranged from 3.2 to 5.9 points among people with anti-AChR antibodies and from three to seven points among those with anti-MuSK antibodies.
Across the study population, mean improvements of about three points on the MG-ADL scale and four points on the QMG scale — both clinically meaningful — were maintained through 130 weeks, or about 2.5 years, of repeated Rystiggo cycles.
Across repeated cycles, more than 60% of patients had a clinically meaningful improvement on each of the MG-ADL, MGC, and QMG scales. More than a quarter achieved minimal symptom expression — an MG-ADL score of zero or one, indicating little to no effect on daily activities — in cycle three, with the proportion reaching 47.1% in cycle 13.
Corticosteroid use declined in some patients
Among the 67 participants who had received at least two consecutive symptom-driven treatment cycles and were taking corticosteroids at baseline, 37.3% reduced their dose and 17.9% stopped corticosteroids entirely by their last follow-up visit during Rystiggo treatment.
Consistent with Rystiggo’s mechanism of action, blood IgG levels decreased rapidly and remained reduced across all treatment cycles. Across cycles one through 13, the median percentage decrease in IgG from the start of each cycle to day 43 ranged from 59.29% to 71.45%. Anti-AChR and anti-MuSK antibody levels also decreased in line with total IgG levels.
Roughly 27% of evaluable patients developed antibodies against Rystiggo after one treatment cycle, rising to 61.2% after seven cycles. These antibodies did not appear to affect improvements on the MG-ADL scale, and treatment-emergent adverse-event rates were generally similar between patients who did and did not develop them.
Treatment-emergent adverse events occurred in 175 of 188 patients (93.1%) and were mostly mild or moderate. The most common were headache (50%), followed by diarrhea (33.5%), COVID-19 (21.8%), and fever (20.7%). The incidence of adverse events remained generally stable across repeated treatment cycles among patients who remained in the study at each cycle. None of the six deaths reported during the studies or post-study follow-up was considered related to Rystiggo by the investigators.
“Data indicate that [Rystiggo] has an acceptable safety profile and is generally well tolerated, providing further evidence for the use of [Rystiggo] as a potential option for the long-term treatment of gMG,” the researchers concluded.
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