FDA Accepts New Drug Application for Zilucoplan for Generalized Myasthenia Gravis

Officials with the FDA have accepted a New Drug Application (NDA) for zilucoplan, a peptide inhibitor of complement component 5 (C5 inhibitor), for the treatment of generalized myasthenia gravis in adult patients who are acetylcholine receptor antibody positive (AChr-Ab+).

Zilucoplan is a subcutaneous, self-administered C5 inhibitor. It was granted orphan drug designation by the FDA in 2019 for the treatment of myasthenia gravis, although it is not currently approved for use in any indication by any regulatory authority worldwide.

Generalized myasthenia gravis (gMG) is a chronic autoimmune 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 nerves’ ability to stimulate the muscle and results in a weaker muscle contraction.

Patients living with myasthenia gravis can have a variety of symptoms, including drooping eyelids, double vision, and difficulty swallowing, chewing, or talking, as well as severe muscle weakness that can result in life-threatening weakness of the muscles used in respiration. The prevalence of myasthenia gravis in the United States is estimated at 14 to 20 per 100,000 individuals. In Europe, the prevalence is estimated to be 10 per 100,000 population.

“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 for support the gMG community,” said Charl van Zyl, executive vice president of neurology solutions and head of European Union/international markets at UCB, in a press release. “Our goal is to provide a solution that can help meet these needs and transform lives.”

The FDA acceptance follows the recent European Medicines Agency (EMA) validation of the Marketing Authorization Application (MAA) for zilucoplan for adults with AChR-Ab+ gMG and who require treatment in addition to steroids or non-steroidal immunosuppressants. Both submissions are based on data from the pivotal phase 3 RAISE study, which randomized 174 adult patients to receive daily subcutaneous, self-administered doses of placebo or zilucoplan 0.3 mg/kg.

The trial demonstrated at week 12 that treatment with zilucoplan resulted in clinically meaningful and statistically significant improvements in key gMG-specific outcomes. 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.

Additionally, 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.

“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 toward approval for this medicine,” van Zyl said in the press release. “We look forward to working with the FDA and EMA to help bring this important new treatment option to patients.”

REFERENCE

UCB announces US FDA acceptance of new drug application and EMA MAA validation for zilucoplan for the treatment of generalized myasthenia gravis in adult patients. News release. UCB; November 14, 2022. Accessed November 14, 2022. https://www.ucb-usa.com/stories-media/UCB-U-S-News/detail/article/ucb-announces-us-fda-acceptance-of-new-drug-application-and-ema-maa-validation-for-zilucoplan-for-the-treatment-of-generalized-myasthenia-gravis-in-adult-patients