AstraZeneca's Long-Acting C5 Inhibitor Ultomiris Receives FDA Priority Review for Generalized Myasthenia Gravis with Onset as Early as Week 1 and Sustained Efficacy Through 52 Weeks

December 20, 2021 /BioValleyBIOON/ --AstraZenecaAstraZeneca recently announced that the U.S. Food and Drug Administration (FDA) has acceptedLong-Acting C5 Complement Inhibitor Ultomiris (Ravulizumab) for the Treatment of Adult Patients with Generalized Myasthenia Gravis (gMG)The supplemental Biologics License Application (sBLA) was submitted for priority review. After AstraZeneca's rare disease unit, Alexion, utilized a Rare Pediatric Disease Priority Review Voucher (PRV),FDAThe PDUFA target date for this sBLA has been set for the second quarter of 2022.

Currently, the regulatory application for Ultomiris in treating gMG is also under review by the European Union and Japanese regulatory authorities. Generalized Myasthenia Gravis (gMG) is a rare, debilitating, chronic autoimmune disease.AutoimmuneNeuromuscular diseases, which can lead to loss of neuromuscular function and severe weakness. In the United States, there are an estimated 64,000 patients with gMG.

Alexion CEO Marc Dunoyer said, "The C5 complement inhibitor Soliris (eculizumab) is the first new therapy approved for the treatment of this devastating disease in nearly 60 years. The new indication application for Ultomiris in the treatment of gMG reflects Alexion's continued commitment to improving outcomes for patients with gMG. The Phase 3 trial demonstrated...Ultomiris can help a wider range of patients, including those with milder symptoms or those in the early stages of their treatment journey."

In the United States, the sBLA for Ultomiris in the treatment of gMG is based on a Phase 3Clinical TrialPositive results. Alexion announced the relevant data in July 2021, which showed:Ultomiris demonstrated efficacy as early as Week 1 of treatment and sustained through Week 52 (26-week randomized controlled period + 26-week open-label extension period).Specifically, patients receiving Ultomiris showed a statistically significant change in the total score of the Myasthenia Gravis–Activities of Daily Living (MG-ADL, a patient-reported assessment) from baseline. Furthermore, for the subset of patients who have completed the 26-week extension study to date, positive efficacy was maintained after a total of 52 weeks of treatment. In the study, Ultomiris was well-tolerated, with a safety profile consistent with the Phase 3 studies in paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS).

In recent years, the treatment field for gMG has developed rapidly, but there are still unmet medical needs. The results from the Ultomiris Phase 3 study reinforce the critical role of complement inhibition in treating gMG, which will provide more patients with the opportunity to receive early treatment using a drug with a mechanism of action that protects neuromuscular function.

The approval and marketing of Soliris is an important first step in addressing the urgent treatment needs of patients with severe symptoms and complications of myasthenia gravis (MG), and it represents the first new therapy for this devastating disease in over 60 years. The results of the Phase 3 study indicate that Ultomiris can benefit a broader patient population than those in the Soliris Phase 3 trial, including patients with milder symptoms or those in the early stages of the disease, while still providing clinically meaningful benefits. These benefits were observed as early as the first week and sustained through 52 weeks. These data suggest that,Ultomiris has the potential to become the new standard of care for gMG and may reduce the treatment burden on patients through its extended dosing interval, thereby improving treatment adherence and patient satisfaction.

In December 2020, AstraZeneca announced a $39 billion cash-and-stock acquisition of Alexion. This acquisition was successfully completed in July 2021.This acquisition is the largest one conducted by AstraZeneca since its establishment in 1999 through the merger of two pharmaceutical companies from the UK and Sweden.The successful completion of this acquisition marks AstraZeneca's entry into the rare disease drug field, opening a new chapter for AstraZeneca.

Alexion's leading products are two complement C5 inhibitors, Soliris and Ultomiris, the latter being the long-acting version of the former. Both drugs function by inhibiting the C5 protein in the terminal part of the complement cascade. The complement cascade is a part of the immune system, and its uncontrolled activation plays a significant role in various severe rare and ultra-rare diseases.

Soliris was first approved for marketing in 2007 and has since been approved for various ultra-rare diseases, including: paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolysis.UremiaSyndrome (aHUS), Generalized Myasthenia Gravis (gMG), Neuromyelitis Optica Spectrum Disorder (NMOSD). Ultomiris is an upgraded version of Soliris, a second-generation, long-acting C5 complement inhibitor, which was first approved for marketing at the end of 2018. The approved indications include: PNH, aHUS.

Soliris is one of the best-selling rare disease drugs globally, with sales reaching $4.065 billion in 2020. Ultomiris achieved sales of $1.077 billion in 2020.Total Sales of Two C5 Inhibitors Reach $5.142 Billion. (Bioon.com)

Source of the original text:Ultomiris regulatory submission accepted under FDA Priority Review in the US for adults with generalised myasthenia gravis