The US Food and Drug Administration (FDA) has asked AstraZeneca to modify the Risk Evaluation and Mitigation Strategy (REMS) programme for the rare disease drug Ultomiris (ravulizumab-cwvz) before granting it a label expansion.

However, the company was quick to note that the FDA did not request any additional clinical and safety data. Ultomiris is a high-grossing drug for AstraZeneca, generating $1.36bn in sales in the first half of 2023, as per the company’s Q2 financial report.

Ultomiris is a long-acting inhibitor of the C5 complement protein, involved in the modulation of the body’s immune system. It is approved in the US to treat patients with paroxysmal nocturnal haemoglobinuria, and patients with atypical haemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy (TMA).

AstraZeneca is now trying to gain a label expansion of Ultomiris in anti-aquaporin-4 (AQP4) antibody-positive (Ab+) approved for neuromyelitis optica spectrum disorder (NMOSD) patients based on Phase III trial (NCT04201262) data. The therapy is approved for NMOSD in multiple regions, including the European Union (EU) and Japan.

NMOSD is a rare immune disease that affects the central nervous system. As part of the CRL, the FDA has asked for Ultomiris’s REMS to be strengthened to further validate the risk of therapy versus the potential risks in anti-aquaporin-4 (AQP4) antibody-positive (Ab+) NMOSD patients who have either received prophylactic antibiotics or meningococcal vaccination prior to treatment. Patients with the anti-aquaporin-4 (AQP4) antibody produce AQP4-targeting antibodies, which can lead to the inflammation of the optic nerve (optic neuritis) and spinal cord (myelitis).

The company plans to work with the FDA to ascertain the next steps regarding REMS modification and stated in its press release: “[AstraZeneca] remains committed to bringing Ultomiris to people living with NMOSD in the US as quickly as possible.”