UCB, a global biopharmaceutical company, today announced that the U.S. Food and Drug Administration (FDA) has accepted for review the New Drug Application (NDA) for its investigational treatment, zilucoplan.
Zilucoplan is a subcutaneous (SC), self-administered peptide inhibitor of complement component 5 (C5 inhibitor) for the treatment of adult patients with acetylcholine receptor antibody positive (AChR-Ab+) generalized myasthenia gravis (gMG).
In 2019, the U.S. FDA granted orphan drug designation to zilucoplan for the treatment of MG. (1) The safety and efficacy of zilucoplan have not been established and it is not currently approved for use in any indication by any regulatory authority worldwide.
This acceptance follows the recent European Medicines Agency (EMA) validation of the Marketing Authorization Application (MAA) for zilucoplan for the treatment of adult patients with AChR-Ab+ gMG and who require treatment in addition to steroids or non-steroidal immunosuppressants. Validation confirms that the application is complete and the formal review process by the EMA’s Committee for Medicinal Products for Human Use (CHMP) can begin. Orphan designation was granted in 2022 by the European Commission to zilucoplan for the treatment of myasthenia gravis. (2)
gMG is a chronic and unpredictable auto-immune disease in which pathogenic autoantibodies can impair synaptic transmission at the neuromuscular junction by targeting specific proteins on the post-synaptic membrane. This disrupts the ability of the nerves to stimulate the muscle and results in a weaker contraction.4 People living with MG can experience a variety of symptoms, including drooping eyelids, double vision, and difficulty in swallowing, chewing and talking, as well as severe muscle weakness that can result in life-threatening weakness of the muscles of respiration. (3) In the U.S. the prevalence of MG is estimated at 14 to 20 per 100,000 population; approximately 36,000 to 60,000 cases. (4) In Europe, the prevalence is estimated at 10 per 100,000 population. (5)
“People living with gMG experience high treatment burden, on top of the debilitating impact of the condition, and there is a clear need for additional targeted treatments to support the gMG community. Our goal is to provide a solution that can help meet these needs and transform lives,” said Charl van Zyl, Executive Vice President Neurology Solutions & Head of EU/International Markets, UCB. “The acceptance of the NDA by the FDA as well as the acceptance of the MAA by the EMA, brings us one step further on our journey towards approval for this medicine. We look forward to working with the FDA and EMA to help bring this important new treatment option to patients.”
The NDA and MAA are based on data from the pivotal Phase 3 RAISE study (NCT04115293), which demonstrated at week 12 that treatment with zilucoplan (0.3 mg/kg daily) resulted in clinically meaningful and statistically significant improvements in key gMG-specific outcomes compared with placebo in patients with AChR-Ab+ gMG. The study met its primary endpoint with zilucoplan showing a placebo-corrected mean improvement of 2.09 points in the Myasthenia Gravis Activities of Daily Living (MG-ADL) score at week 12 (p<0.001). (6)
Zilucoplan demonstrated a favorable safety and tolerability profile, showing a similar rate of treatment-emergent adverse events (TEAEs) between zilucoplan (76.7%) and placebo (70.5%). The most common TEAEs were injection site bruising, headache, and diarrhea. Rates of treatment discontinuation due to a TEAE were low and all patients who completed the 12-week treatment period have entered the ongoing RAISE-XT open-label extension study (NCT04225871). (6,7)
In the RAISE study, 174 adult patients were randomised to receive daily SC, self-administered doses of placebo (N=88) or zilucoplan 0.3 mg/kg (N=86). Patient demographics and baseline disease characteristics were generally balanced between treatment arms. (6)
As a complement C5 inhibitor, zilucoplan is a targeted therapy that inhibits key components in the underlying pathophysiology of gMG, addressing the underlying mechanism of neuromuscular junction damage. (8,9)
“We are deeply committed to improving outcomes for the gMG community. People who live with gMG suffer unpredictable, fluctuating, and debilitating symptoms, which have a huge impact on their lives. We want to help reduce the day-to-day burden of this challenging disease,” said Iris Loew-Friedrich, Executive Vice-President and Chief Medical Officer at UCB. “If approved, zilucoplan has the potential to address the unmet need for people with gMG by providing targeted improvements in signs and symptoms of gMG disease activity and severity. A benefit of targeted treatment is that it may help reduce the adverse events that can be associated with non-specific immunosuppressive treatment of gMG.”
UCB anticipates making regulatory filings for zilucoplan in gMG in Great Britain, Japan, and rest of the world from Q3 2022 onwards.
Alongside zilucoplan, UCB is also investigating rozanolixizumab, a SC-administered, humanized monoclonal antibody that specifically binds, with high affinity, to human neonatal Fc receptor (FcRn), as a potential treatment for gMG. UCB anticipates filing regulatory submissions for rozanolixizumab later this year.