RARE Daily

FDA Wants REMS Modification Before Approving Ultomiris for NMOSD

September 6, 2023

Rare Daily Staff

The U.S. Food and Drug Administration said it would not expand the approval for Alexion, AstraZeneca Rare Disease’s Ultomiris to include the rare, autoimmune condition neuromyelitis optica spectrum disorder without modifications to enhance the Risk Evaluation and Mitigation Strategy.

The company was seeking approval for Ultomiris in adults with neuromyelitis optica spectrum disorder (NMOSD) who are anti-aquaporin-4 (AQP4) antibody positive (Ab+).

The FDA wants the REMS modified to further validate patients’ meningococcal vaccination status or prophylactic administration of antibiotics prior to treatment. The agency did not request additional analysis or reanalysis of the phase 3 CHAMPION-NMOSD trial data included in the application and did not raise concerns about the efficacy or safety data from the trial. The company said it is working closely with the FDA regarding next steps for the REMS modifications.

NMOSD is a condition in which the immune system is inappropriately activated to target healthy tissues and cells in the central nervous system. Approximately three-quarters of people with NMOSD are anti-AQP4 Ab+, meaning they produce antibodies that bind to a specific protein, AQP4. This binding can inappropriately activate the complement system, which is part of the immune system and is essential to the body’s defense against infection, to destroy cells in the optic nerve, spinal cord, and brain.

It most commonly affects women and begins in the mid-30s. Men and children may also develop NMOSD, but it is even rarer. People with NMOSD may experience vision problems, intense pain, loss of bladder/bowel function, abnormal skin sensations, and impact on coordination and/or movement. Most people living with NMOSD experience unpredictable relapses, also known as attacks. Each relapse can result in cumulative disability including vision loss, paralysis, and sometimes premature death.  NMOSD is a distinct disease from other CNS diseases, including multiple sclerosis. The journey to diagnosis can be long, with the disease sometimes misdiagnosed.

Ultomiris, the first and only long-acting C5 complement inhibitor, provides immediate, complete, and sustained complement inhibition. The medication works by inhibiting the C5 protein in the terminal complement cascade, a part of the body’s immune system. When activated in an uncontrolled manner, the complement cascade over-responds, leading the body to attack its own healthy cells. Ultomiris is administered intravenously every eight weeks in adult patients, following a loading dose.

Ultomiris is currently approved for the treatment of certain adults with NMOSD in the European Union, Japan, and other countries. Ultomiris is approved by the FDA for the treatment of adult patients with generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) Ab+, and certain adults and children with paroxysmal nocturnal hemoglobinuria (PNH) or atypical hemolytic uremic syndrome (aHUS).

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