Roche's innovative drug Crovalimab is about to be launched in China, and the complement drug market ushered in new changes

On August 10, the National Medical Products Administration (NMPA) officially accepted the application submitted by Roche for the launch of Crovalimab (Crolizumab Injection), an innovative drug for the treatment of paroxysmal nocturnal hemoglobinuria (PNH), in Chin.

Source: CDE official website

PNH is a rare and fatal blood system disease, with an incidence of about 1 to 10 cases per million population, mostly young adults, and about 77% of patients aged 20 to 40. An epidemiological survey was conducted in China from 1985 to 1994, and the results showed that the incidence of PNH was 8 people/million peopl.

The pathogenesis of PNH is that the mutation of the PIG-A gene leads to a defect in the synthesis of glycoinositol phospholipids (GPI), so that CD55 and CD59 cannot be bound to the cell membrane of red blood cells, resulting in the loss of their function of inhibiting the activation of the complement pathwa.

Among them, CD55 (decay accelerating factor) and CD59 (membrane attack complex inhibitor) are glycosylated GPI-anchored proteins, and their role is mainly to protect host cells from being attacked by the complement system and solubilize.

Currently, apart from hematopoietic stem cell transplantation, there is no effective cure for PN.

Complement is a complex protein network consisting of more than 30 proteins, so it is also called the complement system and is part of the innate immune syste.

01 Alexion approved two complement inhibitors, monopolizing PNH for several years

Since the discovery of the complement system in the 19th century, research on the complement system and its drug development has never stoppe.

As the world's first approved C5 complement inhibitor, Soliris became the only approved treatment for PNH at that tim.

At the end of 2018, Alexion's better long-acting C5 complement inhibitor Ultomiris (ravulizumab) was launched, further consolidating Alexion's leadership in the field of complement drug.

In December 2020, AstraZeneca paid $39 billion to acquire Alexion, given its position in the complement system-mediated orphan disease drug spac.

It is worth noting that the expansion of new indications for Ultomiris has been on the way, but not all have been successfu.

02 The C3 complement inhibitor Empaveli was approved, forming a tripartite situation

On May 15, 2021, Apellis Pharmaceuticals announced that the .

Empaveli is a C3 complement inhibitor designed to modulate excessive complement activation in many disease.

The mechanism of action of Empaveli (Image source: Apellis official website)

The approval of Empaveli is based on the results of the Phase III clinical trial PEGASU.

Empaveli represents the first new type of complement drug in nearly 15 year.

03 Crovalimab is approved for listing, the existing pattern may change

Crovalimab is a humanized complement inhibitor C5 monoclonal antibod.

In addition, crovalimab improves the effectiveness and convenience of existing PNH therapie.
As a subcutaneous injection, crovalimab has unparalleled advantage.
It can be self-administered subcutaneously once every 4 weeks, which is more convenien.
It is worth noting that Crovalimab may become Roche's first innovative drug with China as the world's first launch countr.
The approval of crovalimab is bound to bring a new pattern to the current PNH treatmen.

In addition to the above four complement inhibitors, there are currently a number of drugs under development, such as Sanofi's sutimlimab, Novartis' iptacopan (LNP023), Vifor Pharmaceuticals/ChemoCentryx's avacopan (CCX168), Akari's nomacopan, and Achillion's danicopan, Annexon's ANX005, Ra's zilucoplan,et.

However, due to the fact that there are no less than 100 diseases mediated by complement, currently approved drugs and drugs under development are far from meeting clinical need.
It can be said that the complement drug market is still a veritable blue ocean, and we will wait and see who will get a share of i.

References:

AstraZeneca's Ultomiris scores its 3rd FDA approval, setting up market clash with argenx;

AstraZeneca's Alexion Scores Third FDA Approval For Ultomiris;

Chen Fangfei, Han Bin.
Research progress of complement inhibitors in the treatment of paroxysmal nocturnal hemoglobinuria [J.
Journal of Clinical Hematology, 2021, 34(11): 819-82 DOI: 113201/.
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Chinese expert consensus on the diagnosis and treatment of paroxysmal nocturnal hemoglobinuria[J.
Chinese Journal of Hematology, 2013(03):276-27