AstraZeneca Submits NDA for Ravulizumab (Ultomiris), a Long-Acting C5 Complement Inhibitor Acquired in $39 Billion Alexion Deal, to China's CDE

On December 30, the CDE website showed that the listing application for the complement C5 inhibitor Ravulizumab injection (ravulizumab, Ultomiris) was accepted by the CDE.

Ravulizumab is a long-acting complement C5 inhibitor that was first approved by the FDA in December 2018 for the treatment of paroxysmal nocturnal hemoglobinuria (PNH), marketed under the brand name Ultomiris. In September 2021, a new indication for ravulizumab was approved by the FDA for the treatment of adult and pediatric (over one month old) patients with atypical hemolytic uremic syndrome (aHUS). In April 2022, the third indication for ravulizumab was approved by the FDA for the treatment of adult patients with generalized myasthenia gravis (gMG).

In 2023, Relitolizumab was approved for clinical use in China for the first time. Currently, AstraZeneca has launched two Phase III studies in China: one for preventing severe renal adverse events in chronic kidney disease patients during cardiopulmonary bypass, and the other for treating thrombotic microangiopathy (TMA) following hematopoietic stem cell transplantation (HSCT) in adults and adolescents.

Alexion is a pioneer in complement biology research, having developed Soliris (eculizumab), the world's first complement C5 inhibitor, and Ultomiris (ravulizumab), the first long-acting C5 complement inhibitor. In December 2020, AstraZeneca acquired Alexion for $39 billion, gaining these two key marketed products.

Eculizumab was approved for marketing in China in September 2018 and has been successively approved for the treatment of pediatric and adult PNH and aHUS. Compared with eculizumab, which is injected once every 2 weeks, ravulizumab only needs to be administered intravenously once every 8 weeks, reducing the number of annual doses for patients from 26 to 6.

The difference between Ravulizumab and Eculizumab lies in four amino acid substitutions, which promote the dissociation of the Ravulizumab-C5 complex in endosomes, leading to the lysosomal degradation of C5. Meanwhile, due to the enhanced affinity of Ravulizumab for FcRn, it can return to the bloodstream.

According to AstraZeneca's financial report, the global sales of Eculizumab and Ralizumab in 2022 were $3.762 billion and $1.965 billion, respectively.

In the field of complement inhibitors, pharmaceutical giants such as AstraZeneca, Roche, and Novartis are all actively involved, with continuous competition. AstraZeneca has been continuously iterating and upgrading, from Eculizumab to Ralizumab, and now to the third-generation C5 inhibitor Gefurulimab, a mini-bispecific antibody (25kD) that only includes the heavy chain variable region of an antibody targeting C5 and an antibody fragment that specifically binds to Albumin. Its smaller molecular weight allows for better permeability, and its binding to albumin can extend its half-life, making it a promising once-weekly subcutaneous injection therapy that could potentially be administered at home.

Roche's C5 monoclonal antibody, crovalimab, has entered the submission stage for market approval in China. Patients can receive subcutaneous injections once every 4 weeks. It is expected to become Roche's first innovative drug with China as the global launch site, ahead of its release in Europe and the United States. Novartis' first-in-class complement B factor inhibitor, iptacopan, has also joined the competition and entered the submission stage for market approval in China. The advantage of this drug is that it is orally administered.

Copyright © 2023 PHARMCUBE. All Rights Reserved.

Welcome to forward, share, and reasonably cite. When citing, please clearly indicate the source of the article; if you need to reproduce it, please leave a message to the WeChat Official Account's backend or send a message, and specify the name and ID of the official account.

Disclaimer: The information in this WeChat article is for general reference only and should not be directly used as decision-making content. PharmaCube assumes no responsibility for any loss incurred by any party due to the use of the content herein.