FDA Accepts Second UCB Application for Generalized Myasthenia Gravis

The FDA has accepted for priority review UCB’s biologic license application (BLA) rozanolixizumab, a monoclonal antibody to treat adults with generalized myasthenia gravis (gMG). Generalized myasthenia gravis is chronic and unpredictable autoimmune disease that causes weakness in the skeletal muscles, including those in the arms and legs and those involved in breathing. The condition worsens with activity.

People living with gMG can experience a variety of symptoms, including drooping eyelids, double vision, and difficulty in swallowing, chewing and talking. 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.

Iris Loew-Friedrich, Ph.D.

“Patients living with MG may experience high disease and treatment burden resulting in a significant impact on their daily lives. If approved, rozanolixizumab has the potential to address unmet needs of gMG patients,” Iris Loew-Friedrich, Ph.D., executive vice president and chief medical officer at UCB, said in a press release.

Rozanolixizumab is a subcutaneous monoclonal antibody targeting the neonatal Fc receptor (FcRn). If approved, it would be indicated for patients who are positive for the anti-acetycholine receptor (AChR) or the anti-muscle-specific tyrosine kinase (MuSK) antibody. Rozanolixizumab was also accepted for review by the European Medicines Agency. Decisions from both agencies are expected in the second quarter of 2023.

Related: FDA Accepts NDA for Generalized Myasthenia Gravis Therapy

This is the second therapy from UCB to be accepted for FDA review to treat patients with generalized myasthenia gravis. Zilucoplan, subcutaneous, self-administered peptide inhibitor of complement component 5, is a targeted therapy that inhibits key components in the underlying pathophysiology of generalized myasthenia gravis. The anticipated PDUFA date is in the fourth quarter of 2023.

“Through rozanolixizumab and zilucoplan, we intend to bring two medicines with different mechanisms of action that have the potential to provide targeted treatment options to patients,” Loew-Friedrich said. “With our gMG pipeline, we hope to address both drivers of disease pathology and which account for approximately 95% of people living with gMG.”

Both the FDA and EMA applications for rozanolixizumab were supported by the pivotal phase 3 MycarinG study, in which rozanolixizumab demonstrated statistically significant and clinically meaningful improvements in MG-specific outcomes. In the primary endpoint, rozanolixizumab significantly reduced MG-ADL from baseline to day 43. A greater percentage of patients in the rozanolixizumab 7mg/kg and 10mg/kg arms than the placebo arm achieved a 2.0-point or greater improvement in MG-ADL, a 3.0-point or greater improvement in Quantitative Myasthenia Gravis scores and a 3.0-point or greater improvement in Myasthenia Gravis Composite scores.

The most frequently reported treatment-related adverse events were headache, diarrhea, pyrexia, and nausea. A higher incidence of headache was reported in the rozanolixizumab groups versus placebo, with most cases mild to moderate and severe cases generally managed with non-opioid analgesics. Treatment discontinuation rates due to adverse events were low.