UCB has announced RYSTIGGO (rozanolixizumab-noli) has been approved by the US Food and Drug Administration (FDA) for the treatment of common myasthenia gravis (gMG) in adult patients with anti-acetylcholine receptor (AchR) or anti-muscle specific tyrosine kinase (MuSK) antibodies. positive.
Rozanolixizumab-noli injection for subcutaneous infusion is a humanized IgG4 monoclonal antibody that binds to the neonatal Fc receptor (FcRN), resulting in reduced circulating IgG.
It is the only FDA-approved treatment in adults for anti-AChR and anti-MuSK antibody-positive gMG, the two most common gMG subtypes.
About general myasthenia gravis
gMG is a rare disease with a global prevalence of 100 to 350 cases per 1 million people. People living with gMG may experience a variety of symptoms, including severe muscle weakness which can result in life-threatening respiratory muscle weakness, double vision, drooping eyelids, and difficulty swallowing, chewing, and speaking.
In gMG, pathogenic autoantibodies can interfere with synaptic transmission at the neuromuscular junction (NMJ) by targeting specific proteins on the post-synaptic membrane. This impairs the nerves’ ability to stimulate the muscles and results in weaker contractions. gMG can occur in any race, sex or age.
“gMG can cause unpredictable fluctuations in symptom severity and frequency, which are often debilitating and can have a major impact on a patient’s life. People living with gMG often face a wide range of treatment options, and those that have traditionally only offered symptom relief,” said Vera Bril, Professor of Medicine (Neurology), University of Toronto, Director of the Neuromuscular Section, Division of Neurology, University of Toronto and University Health Network, Toronto, and principal investigator of the MycarinG.
“There is a significant need for new, innovative treatment options to reduce the everyday gMG burden. Rozanolixizumab-noli is a new treatment option, which targets one of the disease mechanisms to provide symptom improvement in patient and clinician-reported outcomes at day 43.”
There is no one-size-fits-all approach
“No two people living with gMG experience the disease in the same way, so we can’t take a ‘one size fits all’ approach to disease management,” said Iris Loew-Friedrich, executive vice president and chief medical officer at UCB. .
“Management of the disease must be based on the clinical needs and preferences of each patient, and the goal of treatment is to help restore the patient’s ability to carry out activities of daily living. The approval of rozanolixizumab-noli means clinicians have additional approved treatment options for their gMG patients who have not found a treatment that meets their needs.”
Phase 3 study
FDA approval is supported by safety and efficacy data from the landmark MycarinG phase 3 study, published in The Lancet Neurology in May 2023. The primary efficacy end point was a comparison of baseline change between treatment groups in total MG-ADL score at day 43. MG-ADL is a measure that assesses the impact of gMG on daily functioning of eight signs or symptoms commonly affected by gMG.
This includes activities such as breathing, speaking, swallowing, and being able to rise from a chair. Each item is rated on a four-point scale where a score of 0 represents normal functioning and a score of 3 represents loss of ability to perform that function. Total scores range from 0 to 24, with higher scores indicating more distraction. A statistically significant difference in favor of rozanolixizumab-noli was observed in the change in total MG-ADL score from baseline.
The secondary end point was the change between treatment groups from baseline to day 43 at QMG. QMG is a 13 item category scoring system that assesses muscle weakness. Each item is rated on a four-point scale where a score of 0 represents no weakness and a score of 3 represents severe weakness. The possible total score ranges from 0 to 39, where a higher score indicates a more severe disorder. A statistically significant difference in favor of rozanolixizumab-noli was observed in the change in QMG total score from baseline.
The most common adverse reactions (reported in at least 10% of patients treated with rozanolixizumab-noli) were headache, infection, diarrhea, pyrexia, hypersensitivity reactions, and nausea.
“We want to thank UCB for their continued commitment to the MG community to bring new, FDA-approved treatment options for common myasthenia gravis to patients and the doctors who care for them,” said Samantha Masterson, president and CEO of the Myasthenia Gravis Foundation of America (MGFA). .
“People living with generalized myasthenia gravis continue to have significantly unmet medical needs, which means expanding the number of FDA-approved treatment options is critical to treating this chronic, autoimmune, neuromuscular disease.”
Europe and Japan
Rozanolixizumab-noli will be commercially available in the US during the third quarter of 2023.
“Building on our decades of experience in neurology and immunology, we are proud to support the MG community with solutions to help improve patients’ lives, including new FDA-approved treatments, education, and support,” said Loew-Friedrich.
“The approval following a priority review of rozanolixizumab-noli is testament to the drug’s potential as a generally well-tolerated treatment option targeted to individual patient needs. We are deeply grateful to the patients, treatment partners and researchers who participated in the MycarinG study, and to our employees and collaborators, whose dedication and commitment to the MG community made this important achievement possible.”
An orphan designation was granted by the European Commission in April 2020 to rozanolixizumab for the treatment of generalized myasthenia gravis. The Japan Pharmaceuticals and Medical Devices Agency (PMDA) granted similar status to rozanolixizumab in Japan in November. Response from regulatory agencies to this submission is expected in Semester 1 2024.
Rozanolixizumab is a subcutaneously administered humanized monoclonal antibody that specifically binds, with high affinity, to the human neonatal Fc receptor (FcRn). It has been designed to block the interaction of FcRn and Immunoglobulin G (IgG), accelerate antibody catabolism and reduce the concentration of pathogenic IgG autoantibodies.