• 19 Sep 2024
• Admin
• News Article

Sysmex Applies for Manufacturing and Marketing Approval of an Assay Kit

Sysmex Applies for Manufacturing and Marketing Approval of an Assay Kit to Predict the Risk of Adverse Reactions from Anti-amyloid β Antibody Drugs for Alzheimer’s Disease

Overview

Sysmex Corporation announces that it has filed a manufacturing and marketing approval application in Japan for an assay kit that determines the APOE genotype1 in blood genomic DNA to predict the risk of adverse reactions from anti-amyloid β antibody drugs (“the assay kit”) on September 13, 2024.

Development of Anti-Amyloid β Antibody Drugs

• In recent years, vigorous development of anti-amyloid β antibody drugs that act on the pathological mechanism of Alzheimer’s disease has been underway both in Japan and internationally. 
• While anti-amyloid β antibody drugs are expected to be effective, they are known to be associated with an adverse reaction called Amyloid-Related Imaging Abnormalities2 (ARIA) in some recipients. 
• The incidence of ARIA reportedly varies depending on the APOE genotype.3

Sysmex has submitted a manufacturing and marketing approval application for an assay kit to determine the APOE genotype.4 In the future, if the assay kit covered by national health insurance, it is expected that in clinical practice, physicians, patients, and their families will be able to discuss the risk of developing ARIA when considering the administration of anti-amyloid β antibody drugs.

Sysmex Involvement for Dementia

• Sysmex is engaged in developing new testing and diagnostic technologies for dementia that contribute to the early diagnosis, the selection of effective treatments, and monitoring of therapeutic effects. 
• Sysmex has been marketing testing kits in Japan, the United States, and European countries that detect the accumulation of amyloid β in the brain, a cause of Alzheimer’s disease, using small blood samples. 
• We will continue to support each individual’s healthcare journey, assist in the selection of appropriate treatments and contribute to the creation of new value for a healthy society. 

Reference

Guidelines for the Proper Use of Cerebrospinal Fluid and Blood Biomarkers and APOE Genotyping for Dementia Version 2, September 30, 2023 (Taskforce for Establishment of Guidelines for the Proper Use of Cerebrospinal Fluid and Blood Biomarkers and APOE Genotyping for Dementia) (Japanese only)
     https://www.neurology-jp.org/news/pdf/news_20231003_03_01.pdf

Terminology

APOE Genotype:

• A gene encoding apolipoprotein E (ApoE), which is involved in lipid metabolism. 
• Three genotypes (ε2, ε3, and ε4) are defined by the combination of two single-nucleotide substitutions (rs429358 and rs7412) encoding amino acids at positions 112 and 158. 
• The incidence rate of ARIA increases in the order of ε4 homozygotes, ε4 heterozygotes, and non-ε4 carriers of APOE. 
• In particular, APOE ε4 homozygotes are more likely to manifest symptomatic ARIA than other genotypes.
• The package inserts for FDA-approved anti-amyloid β antibody drugs* caution as follows: 

Testing for APOE ε4 status should be performed prior to the initiation of treatment to determine the risk of developing ARIA. Prior to testing, prescribers should discuss with patients the risk of ARIA across genotypes and the implications of genetic testing results. It is also stated that prescribers should inform patients that if APOE genotype testing is not performed they can still be treated with these therapeutics, although they cannot be judged to be at higher risks of developing ARIA due to APOE ε4 homozygosity.
*Package insert information (FDA-approved drug products database) [accessed on September 17, 2024].
LEQEMBI (nonproprietary name: lecanemab-irmb)https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761269Orig1s001lbl.pdf
Kisunla (nonproprietary name: donanemab-azbt)https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761248s000lbl.pdf 

• Amyloid-Related Imaging Abnormalities:

Amyloid-Related Imaging Abnormalities (ARIA) are divided into two types: ARIA-E and ARIA-H. The former is characterized by edema with liquid material accumulated around the brain blood vessels. The latter is manifested with microhemorrhages and iron (hemosiderin) deposits in the brain. Although ARIA is usually asymptomatic, serious events have been reported in rare cases.
Source: Hampel H.et al. Amyloid-related imaging abnormalities (ARIA): radiological, biological and clinical characteristics, Brain. 146, 4414-4424 (2023)

https://doi.org/10.1093/brain/awad188      

• Sources:

van Dyck CH., et al. Lecanemab in early Alzheimer's disease. New Engl J Med. 388, 9-21 (2023)
https://www.nejm.org/doi/full/10.1056/NEJMoa2212948
Sims JR. et al. Donanemab in early symptomatic Alzheimer disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial. JAMA 330 512-527 (2023)
https://jamanetwork.com/journals/jama/fullarticle/2807533

• The clinical performance study related to this regulatory application for approval was conducted as a joint research project with Eisai Co., Ltd.

About Sysmex Corporation

• Sysmex Corporation, headquartered in Kobe, Japan, is a global leader in in vitro diagnostics. 
• Since its foundation in 1968, Sysmex has focused on diagnostics as the core of its business, and today, it supports the health of people in over 190 countries and regions worldwide. 
• Sysmex continues to innovate in diagnostics, and to collaboratively create unique values in the areas of personalized medicine and novel treatments, under its long-term vision of ""Together for a better healthcare journey.
• " Through its unique technology, solutions, and co-creation with various partners, Sysmex delivers new value and addresses the universal desire of people to live longer and healthier lives. The company employs more than 10,000 employees worldwide. 
• Sysmex Corporation is listed in the Prime Market on the Tokyo Stock Exchange. For more information about Sysmex, please visit www.sysmex.co.jp/en/.