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

Dec 30, 2023 08:54 CST Updated 08:54

AstraZeneca

Biopharmaceutical Manufacturer

On December 30, the CDE official website showedAstraZenecaThe marketing application for the complement C5 inhibitor Ravulizumab Injection (ravulizumab, Ultomiris) has been accepted by the CDE.

Ravulizumab is a long-acting complement C5 inhibitor, which was first approved for marketing by the FDA in December 2018.For the treatment of paroxysmal nocturnal hemoglobinuria (PNH), marketed under the brand name Ultomiris; In September 2021, ravulizumab received FDA approval for a new indication to treat 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,Relatlimab Granted Clinical Approval in China for the First Time. Currently,AstraZeneca has launched two Phase III studies in China: one for the prevention of severe renal adverse events in patients with chronic kidney disease during cardiopulmonary bypass, using Relitolizumab, and the other for the treatment of 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 PNH and aHUS in both children and adults. Compared with eculizumab, which is administered once every two weeks, ravulizumab only needs to be administered intravenously once every eight 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 Ralitezumab 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 have all made strategic investments, leading to continuous competition. AstraZeneca has been continuously iterating and upgrading its portfolio, from Eculizumab to Ravulizumab, and now to the third-generation C5 inhibitor Gefurulimab, which is 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 phase for market approval in China. Patients can receive subcutaneous injections once every four 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 phase for market approval in China. The advantage of this drug is that it is orally administered.

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