AstraZeneca's Ultomiris Receives FDA Priority Review for New Indication in Generalized Myasthenia Gravis

Source: PharmaCube Info

Author: Shi Bei

On December 21, AstraZeneca announced that the supplemental Biologics License Application (sBLA) for Ultomiris (ravulizumab-cwvz), a complement C5 inhibitor developed by Alexion, the leading company in the complement field it acquired, for the treatment of adult generalized myasthenia gravis (gMG), has been accepted by the FDA and granted Priority Review.

gMG is a rare, debilitating chronic autoimmune neuromuscular disorder that can lead to loss of muscle function and severe weakness. It is estimated that there are 64,000 diagnosed cases of gMG in the United States.

Ultomiris is the first and only approved long-acting C5 complement inhibitor, offering immediate, complete, and sustained complement inhibition. It works by inhibiting the C5 protein at the terminal end of the complement cascade, which is part of the human immune system. When the C5 protein is activated in an uncontrolled manner, the complement cascade overreacts, causing the body to attack its own healthy cells.

This marketing application is based on the results of a Phase III clinical trial evaluating Ultomiris in patients with gMG. By Week 26, patients treated with Ultomiris demonstrated significant improvement in MG-ADL scores from baseline, which was sustained through Week 52 (26-week randomized controlled period + 26-week open-label extension period). In the trial, the safety profile of Ultomiris was consistent with that observed in Phase III trials for paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS). Regulatory submissions for the use of Ultomiris in treating gMG are currently under review by health authorities in the EU and Japan.

Ultomiris and Soliris are the two most important marketed products that AZ acquired through its $39 billion purchase of Alexion. As Ultomiris is currently approved for the treatment of PNH and aHUS, its sales reached $701 million in the first half of 2021, representing a year-on-year increase of 48%.

On August 20, AstraZeneca announced that the Phase III CHAMPION-ALS study of Ultomiris for the treatment of adult amyotrophic lateral sclerosis (ALS) did not meet the clinical endpoint in a pre-specified interim analysis evaluated by the Independent Data Monitoring Committee (IDMC). Based on the committee’s recommendation, Alexion decided to terminate the study early. This marks the first setback for AstraZeneca since completing the acquisition of Alexion on July 21 this year.

Besides ALS, Ultomiris is highly likely to gain approval for expanding its indication to treat Neuromyelitis Optica Spectrum Disorder (NMOSD). According to Alexion's latest R&D progress update in April, the NMOSD trial data might be released in the second half of 2022.

Piper Sandler analyst Christopher Raymond said in a February report that Alexion's global sales revenue for the MG indication could reach $3.06 billion in 2025, with revenue from NMOSD potentially reaching $1 billion.