EHA hot spot: A number of phase III studies of C5 complement inhibitor Crovalimab have entered the recruitment phase, and the research and development in China is synchronized with the global

Paroxysmal nocturnal hemoglobinuria (Paroxysmal nocturnal hemoglobinuria, PNH) is a rare acquired clonal disease of hematopoietic stem cells in which the PIG-A gene mutation on somatic cells xp22.
1 leads to dysregulation of the complement system
.

Different degrees of intravascular hemolysis, bone marrow hematopoietic dysfunction and thrombosis have brought a great disease burden to PNH patients and affected the survival of patients
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In foreign countries, complement C5 inhibitors have become the standard treatment for PNH; however, in China, such drugs are not yet available, and there is still a large unmet need for the treatment of PNH
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A new generation of C5 complement inhibitor, circulating antibody Crovalimab Crovalimab is a new generation of C5 inhibitor engineered through continuous monoclonal antibody recovery technology (Smart-Ig).
It has a long half-life, can be injected subcutaneously, and is the same for patients with C5 polymorphisms.
There is curative effect
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The Phase I/II COMPOSER trial showed superior efficacy and safety data, which enabled crovalimab to enter the phase III clinical trial phase smoothly
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Diagram of the mechanism of action of the Crovalimab circulating antibody: After crovalimab binds to complement C5, it undergoes endocytosis and dissociates under the acidic environment of endosomes, and then C5 is degraded in the lysosome; while crovalimab interacts with the neonatal Fc receptor ( FcRn) is combined to recycle to the outside of the cell for further recycling.
At the 26th European Annual Conference on Blood (EHA) this year, crovalimab announced three important research designs, including two important phase III clinical trials (COMMODORE 1, COMMODORE) 2), and a study related to the burden of PNH disease (COMMODORE BoI)
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01Crovalimab's multiple key phase III clinical trials have entered the recruitment phase (PB1480).
At present, there are 3 crovalimab phase III clinical trials that have entered the recruitment phase around the world.
Among them, COMMODORE 1 and COMMODORE 2 are crovalimab versus eculizumab.
Efficacy and safety studies in PNH patients who have previously received C5 complement inhibitors and have not received C5 complement inhibitor treatment
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In addition, multiple centers in mainland China are conducting COMMODORE 3 trials at the same time.
This single-arm study is to verify the efficacy and safety of crovalimab in PNH patients ≥12 years of age who have not previously received C5 complement inhibitor therapy
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COMMODORE 1 study design plan: C5 complement inhibitor treated population COMMODORE 2 study design plan: naive population COMMODORE 3 (Chinese single-arm trial) study design plan: naïve population 02PNH disease burden study (PB1486) has not yet been tested in C5 complement inhibitors In accessible areas, the incidence of complications such as thrombosis and kidney injury in PNH patients is higher, the quality of life of the patients is poor, and the 5-year mortality rate is about 35%
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In areas where C5 complement inhibitors are accessible, treatment costs, reimbursement problems, differences in drug efficacy, and inconvenience in administration methods, still bring a heavier burden of disease to the medical system and PNH patients
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Therefore, robust data on the real-life burden and cost of PNH are needed to assess the impact of current treatments and establish a baseline for new treatments
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COMMODORE BoI is an international, prevalence-based, bottom-up disease burden study, including retrospective and prospective data collection
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Doctors will use electronic case record forms (eCRF) to provide information about sociodemographic, clinical and medical resource utilization
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At the same time, the patient report outcome (PRO) survey will provide further information on the impact of PNH on the economy and HRQOL
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The study will include a total of 94 doctors from France, Germany, the United Kingdom and China.
They will report 350 patient eCRFs and are expected to collect 140 patient surveys
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Related research results will be announced in early 2022
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Conclusion The clinical trials of Crovalimab are being carried out simultaneously at home and abroad.
It is expected that the clinical research data will be released as soon as possible, and domestic PNH patients can use the standard treatment plan of C5 complement inhibitor as soon as possible
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In addition, there is still a lack of disease burden research in the field of PNH in China.
The development of such research will help to formulate relevant medical and health policies and truly serve patients.
It is hoped that domestic counterparts will work together to explore more effective diagnosis and treatment paths in the field of PNH
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References: 1.
Du, et al.
Int.
Jnl.
Lab.
Hem.
2016, 38, e84–e85.
2.
Fukuzawa T et al, Sci Rep, 2017, Apr 24;7(1):1080.
3.
Nishimura J et al.
N Engl J Med.
2014;370:632-639.
4.
Röth A et al, Blood, 20205.
CTR20201931 and CTR20210827 research information: http:// COMMODORE3 (NCT04654468): https:// COMMODORE 1(NCT04432584): https:// term=crovalimab&draw=2&rank=38.
COMMODORE 2(NCT04434092): https:// stamp "read the original text" and we will make progress together