FDA Accepts NDA for Generalized Myasthenia Gravis Therapy

The FDA has accepted for review UCB’s new drug application (NDA) for zilucoplan to treat adults with generalized myasthenia gravis. If approved, it will treat those who are acetylcholine receptor antibody positive.

Generalized myasthenia gravis is a chronic auto-immune disease that causes weakness in the skeletal muscles that worsens after periods of activity and improves after periods of rest. People living with myasthenia gravis can experience a variety of symptoms, including drooping eyelids, double vision, and difficulty in swallowing, chewing and talking, as well as severe muscle weakness. In the United States, the prevalence of myasthenia gravis is estimated at 14 to 20 per 100,000 population or about 36,000 to 60,000 cases.

Zilucoplan is a subcutaneous, self-administered peptide inhibitor of complement component 5. It is a targeted therapy that inhibits key components in the underlying pathophysiology of generalized myasthenia gravis, addressing the underlying mechanism of neuromuscular junction damage. The anticipated PDUFA date is in the fourth quarter of 2023.

Iris Loew-Friedrich, Ph.D.

“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,” Iris Loew-Friedrich, Ph.D., executive vice president and chief medical officer at UCB, said in a press release. “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.”

The NDA is based on data from the pivotal phase 3 RAISE study, which demonstrated at week 12 that treatment with zilucoplan resulted in clinically meaningful and statistically significant improvements in key generalized myasthenia gravis-specific outcomes compared with placebo in patients. 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 score at week 12.

The most common treatment-emergent adverse events were injection site bruising, headache, and diarrhea. Rates of treatment discontinuation due to a treatment-emergent adverse event were low and all patients who completed the 12-week treatment period have entered the ongoing RAISE-XT open-label extension study. n the RAISE study, 174 adult patients were randomized to receive daily self-administered doses of placebo or zilucoplan.

Additionally, UCB’s marketing authorization application has been accepted by the European Medicines Agency.