AstraZeneca's Ultomiris Third Indication Approved by US FDA!

Recently, AstraZeneca announced that the new indication of Ultomiris (ravulizumab) has been approved by the US Food and Drug Administration (FDA) for the treatment of adult patients with generalized myasthenia gravis (gMG).

The drug is suitable for gMG patients with positive anti-acetylcholine receptor (AChR) antibodies, which account for about 80% of the entire gMG patient population. The approval marks the third indication for Ultomiris, which has previously been approved for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS).

gMG is a rare chronic autoimmune neuromuscular disease that causes loss of neuromuscular function and severe weakness. People with gMG experience severe fatigue, difficulty speaking, swallowing, eating, and even other complications of vision and breathing. Approximately 90,000 patients with gMG are expected in the United States. Despite recent advances, gMG management is complex and early intervention can ensure a certain quality of life.

Notably, Ultomiris is the first long-acting C5 complement inhibitor approved for the treatment of gMG. This approval covers patients with gMG, including those with milder symptoms. In clinical trials, patients treated with Ultomiris showed significant improvement in clinical symptoms and demonstrated early efficacy and durable improvements in activities of daily living.

The approval for the new indication is based on the results of the CHAMPION-MG Phase 3 clinical trial. Results of the trial showed a highly statistically significant change from baseline in the Myasthenia Gravis-Ability of Daily Living Scale (MG-ADL) total score in the Ultomiris-treated group compared with the placebo group at week 26 of treatment. In particular, early efficacy was shown in the first week of Ultomiris treatment and continued to 26 weeks. In this study, Ultomiris was well tolerated, with a safety profile consistent with that observed in Phase 3 clinical trials of PNH and aHUS. The most common adverse reactions in patients receiving Ultomiris were upper respiratory tract infection and diarrhea.

It is reported that Ultomiris and Soliris are two complement C5 inhibitors acquired by AstraZeneca after acquiring Alexion for $39 billion in 2020. Among them, Ultomiris is the long-acting version of Soliris, Soliris is administered every 2 weeks, while Ultomiris is administered every 8 weeks. Ultomiris covers a wider range of patients with gMG, including some patients with milder symptoms.

It is worth noting that the expansion of new indications for Ultomiris has been on the way, but not all have been successful. In August 2021, the CHAMPION-ALS Phase 3 study of Ultomiris in adults with amyotrophic lateral sclerosis (ALS) failed to meet the primary endpoint in a pre-specified interim analysis. The study was terminated early on the recommendation of an independent data monitoring committee. It was also the first setback for AstraZeneca after it completed the Alexion acquisition in July 2021.

Ultomiris is also being developed for the treatment of neuromyelitis optica spectrum disorder (NMOSD), an approved indication for Soliris. The indication is expected to have trial results in the first half of this year and a regulatory filing in the second half of this year.