Source – UCB
On 27 June 2023, UCB faced regulatory challenges in the United States for the second consecutive year, including a delay in the FDA’s review of its application for the plaque psoriasis candidate bimekizumab.
However, UCB received positive news from the FDA, granting approval for Rystiggo (rozanolixizumab-noli) to treat the rare autoimmune condition known as myasthenia gravis (gMG). Rystiggo is a subcutaneously administered monoclonal antibody and the first therapy approved for both subsets of the disorder, namely anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody-positive patients. It should be noted that AstraZeneca and argenx already have approved therapies for gMG. Rozanolixizumab-noli will be commercially available in the U.S. during the 3rd quarter of 2023.
In gMG patients, pathogenic IgG autoantibodies disrupt the communication between nerves and muscles, potentially causing life-threatening weakness in the muscles responsible for breathing, swallowing, chewing, and speaking. While the condition can affect individuals of any age, it is more commonly observed in young women and men aged 50 and older, often presenting symptoms such as double vision and drooping eyelids.
“gMG can cause unpredictable fluctuations in severity and frequency of symptoms, which are often debilitating and can substantially impact the lives of patients. People living with gMG often face treatment options that are broad-acting, and that have traditionally only offered symptomatic relief. There is a significant need for new, innovative treatment options to reduce the day-to-day burden of gMG. Rozanolixizumab-noli is a new treatment option, targeting one of the mechanisms of disease to provide symptom improvement in patient-and physician reported outcomes at day 43.”
– 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 lead investigator of the MycarinG study
Rystiggo works by binding to the neonatal Fc receptor, leading to a decrease in circulating IgG levels. The FDA approval was supported by a phase III trial involving 200 patients with the AChR or MuSK subsets of gMG. The study demonstrated statistically significant improvements in various gMG-specific outcomes, including breathing, walking, talking, and the ability to rise from a chair..
UCB anticipates that Rystiggo will be available in the third quarter, but the pricing details have not been disclosed. The treatment is currently under review in Japan and Europe. Additionally, UCB has another candidate, the complement factor C5 inhibitor zilucoplan, which is nearing approval for the treatment of gMG in the AChR subset. Zilucoplan was obtained through UCB’s acquisition of Ra Pharmaceuticals for $2.5 billion and has shown positive results in a Phase III study.
Competition in the gMG space is fierce, with AstraZeneca’s Ultomiris receiving approval for the indication last year and argenx recently gaining FDA approval for Vyvgart Hytrulo.
The FDA conducted a Priority Review of rozanolixizumab-noli. Additionally, rozanolixizumab is currently undergoing evaluation by the European Medicines Agency (EMA) and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) for the treatment of generalized myasthenia gravis (gMG) in adults. In 2019, the U.S. FDA granted orphan drug designation to rozanolixizumab-noli specifically for the treatment of gMG. Similarly, in April 2020, the European Commission granted orphan designation to rozanolixizumab for the treatment of gMG. The PMDA also provided rozanolixizumab with orphan status in Japan in November. The regulatory agencies are expected to provide responses to these submissions by the first half of 2024.
Additionally, UCB has another potential therapy called zilucoplan, a once-daily C5 inhibitor administered through subcutaneous injections, also currently under regulatory review. Decisions regarding zilucoplan’s approval are expected in the United States and Europe before the end of 2023. If approved, zilucoplan will directly compete with AstraZeneca/Alexion’s Soliris (eculizumab) and it’s longer-acting successor Ultomiris (ravulizumab), both intravenously administered C5 inhibitors, which generated significant revenue in 2022 across various indications including gMG, paroxysmal nocturnal haemoglobinuria (PNH), and atypical haemolytic uraemic syndrome (aHUS).
