Using patent filings and FDA approvals related to in vitro diagnostic devices, we elaborate on the role of companion diagnostics in the advancement of personalized medicine.
Companion Diagnostics (CDx): FDA Approvals and Patent Filings On the Rise
Companion diagnostics (CDx), sometimes called in vitro diagnostic devices (IVD), are diagnostic tests “coupled” with a therapeutic drug to evaluate its applicability to a specific group of patients based on one or more biomarkers. While most companion diagnostic devices and nucleic acid tests are used with a specific therapy, there are others which can help choose the appropriate therapy. Companion diagnostic devices may include kits, assays, and specific software to analyze results, aid in discerning results and make decisions regarding treatment.
Companion diagnostics are particularly relevant in the current era of personalized medicine. Personalized medicine refers to the practice that uses specific patient characteristics to determine the appropriate treatment. Our current practice in personalized pharmaceuticals uses the understanding of the patient’s demographics, history, and environment combined with cutting edge procedures, such as neuroimaging, pharmacogenomics, cellular and molecular phenotyping, and database mining.
Patent filings for companion diagnostics indicate a steady increase in filing activity (illustrated in Figure 1) with US being the top filer contributing 52% of all patent families. China is a distant second with 15% of the first filings. Europe has a little over 1,000 families originating from the European Patent Office, whereas PCT applications claim filing priority for about 200 patent families.
Figure 1: Charts Illustrating the Patent Filing Trend and Map Indicating Geographical Origins of First Filing. EP and PCT Filings Account for about 1000 and 200 Patent Families Respectively
Selected FDA approvals related to nucleic acid based devices since 2015 have been listed below (Table 1). Among these approvals, eighteen (18) of them were Class III devices that required a PMA pathway, whereas nine (9) approvals required de novo pathway for novel medical devices. About 21% of approvals were under the 510(k) premarket notification. 23andMe had the highest approvals (5) relating to nucleic acid based in vitro devices. The not-for-profit, ARUP Laboratories, developed two devices that received approvals under the Humanitarian Device Exemption pathway.
Table 1: FDA Approvals Related to Nucleic acid Based In Vitro Devices Since January 2015
|
Condition |
Kits / Assays/ Systems/ Software |
Approval Pathway |
Company |
Decision Date |
|
Tumor Profiling |
FoundationOne CDx |
PMA |
Foundation Medicine, Inc. |
6-Nov-2019 |
|
Tumor Profiling |
Myriad myChoice CDx |
PMA |
Myriad Genetic Laboratories, Inc. |
23-Oct-2019 |
|
Chronic Myeloid Leukemia |
Xpert BCR-ABL Ultra, GeneXpert Dx System, GeneXpert Infinity-48s And GeneXpert Infinity-80 Systems |
510(k) |
Cepheid |
27-Sep-2019 |
|
Breast Cancer |
Therascreen PIK3CA RGQ PCR Kit |
PMA |
Qiagen GMBH |
28-May-2019 |
|
Breast Cancer |
INFORM HER2 Dual ISH DNA Probe Cocktail |
PMA |
Ventana Medical Systems, Inc. |
3-May-2019 |
|
Urothelial Cancer |
Therascreen FGFR RGQ RT-PCR Kit |
PMA |
Qiagen GmbH |
26-April-2019 |
|
Prostate Cancer |
Progensa PCA3 Assay |
PMA |
Gen-Probe, Inc. |
15-Mar-2019 |
|
Ovarian Cancer |
BRACAnalysis CDx |
PMA |
Myriad Genetic Laboratories, Inc. |
6-Mar-2019 |
|
Chronic Myeloid Leukemia |
QXDx BCR-ABL %IS Kit for use On The QXDx AutoDG DdPCR System |
510(k) |
Bio-Rad Laboratories, Inc. |
13-Feb-2019 |
|
Colorectal Cancer Predisposition |
MUTYH-Associated Polyposis (MAP) |
510(k) |
23andMe |
18-Jan-2019 |
|
Hematologic Malignancies |
MLL (KMT2A) Breakapart FISH Probe Kit; AML1 (RUNX1) Breakapart FISH Probe Kit, P53 (TP53) Deletion FISH Probe Kit; EVI1 (MECOM) Breakapart FISH Probe Kit, DEL(20Q) Deletion FISH Probe Kit; AML1/ETO (RUNX1/RUNXIT1)) Translocation, Dual FUSI, CBFB (CBFB) /MYH11 Translocation, Dual Fusion FISH Probe Kit,DEL(5Q) Deletion FISH Probe Kit; DEL(7Q) Deletion FISH Probe Kit |
De Novo |
Cytocell Ltd. |
21-Dec-2018 |
|
Pharmacogenetic Reports |
23AandMe Personal Genome Service (PGS) Pharmacogenetic Reports |
De Novo |
23andMe |
31-Oct-2018 |
|
Multiple Myeloma / Acute Lymphoblastic Leukemia (MRD) |
Adaptive Biotechnologies CLONOSEQ ASSAY |
De Novo |
Adaptive Biotechnologies Corp |
28-Sep-2018 |
|
Acute Myeloid Leukemia |
Abbott RealTime IDH1 |
PMA |
Abbott Molecular Inc. |
20-Jul-2018 |
|
Coagulation, late-onset Alzheimer’s, Parkinson’s, Celiac, Alpha-1 antitrypsin deficiency, Early-onset primary dystonia, Factor IX deficiency, Gaucher Type 1, Glucose-6-phosphate dehydrogenase deficiency, Hereditary hemochromatosis, Hereditary thrombophilia |
Personal Genome Service (PGS) Genetic Health Risk Test for Hereditary Thrombophilia |
De Novo |
23andME |
6-Apr-2018 |
|
Tissue of Origin |
Tissue of Origin Test Kit – FFPE |
510(k) |
Cancer Genetics, Inc. |
15-Mar-2018 |
|
Breast Cancer |
23andMe PGS Genetic Health Risk Report for BRCA1/BRCA2 (Selected Variants) |
De Novo |
23andMe |
6-Mar-2018 |
|
Myeloproliferative disease/ Polycythemia Vera |
Ipsogen JAK2 RGQ PCR Kit |
510(k) |
Qiagen INC |
12-Jan-2018 |
|
Chronic Myeloid Leukemia |
MRDx BCR-ABL Test, MRDx BCR-ABL Test Software |
510(k) |
MolecularMD Corporation |
22-Dec-2017 |
|
Tumor Profiling |
MSK-IMPACT (Integrated Mutation Profiling of Actionable Cancer Targets):A Hybridization-Capture based Next Generation Sequencing Assay |
De Novo |
Memorial Sloan-Kettering Cancer Center |
15-Nov-2017 |
|
Colorectal Cancer |
Ventana ANTI-MLH-1(M1) Mouse Monoclonal Primary Antibody, Ventana ANTI-PMS2 (A16-4) Mouse Monoclonal Primary Antibody, Ventana ANTI-MSH2 (G219-1129) Mouse Monoclonal Primary Antibody, Ventana ANTI-MSH6 (SP 93) Mouse Monoclonal Primary Antibody, Ventana ANTI-BRAF V600E (VE1) Mouse Monoclonal Primary Antibody |
De Novo |
Ventana Medical Systems |
27-Oct-2017 |
|
Chromosome Abnormalities |
GenetiSure Dx Postnatal Assay |
510(k) |
Agilent Technologies, Inc. |
11-Aug-2017 |
|
Colorectal Cancer |
Praxis Extended RAS Panel |
PMA |
Illumina, Inc. |
29-Jun-2017 |
|
Non-Small Cell Lung Cancer |
Oncomine Dx Target Test |
PMA |
Life Technologies Corp |
22-Jun-2017 |
|
Acute Myeloid Leukemia |
LeukoStrat CDx FLT3 Mutation Assay |
PMA |
Invivoscribe Technologies, Inc. |
28-April-2017 |
|
Breast Cancer |
HER2 CISH pharmDxTM Kit |
PMA |
Dako Denmark A/S |
12-April-2017 |
|
Ovarian Cancer |
FoundationFocus CDxBRCA |
PMA |
Foundation Medicine, Inc. |
19-Dec-2016 |
|
Cystic Fibrosis |
xTAG Cystic Fibrosis 60 Kit v2, xTAG Data Analysis Software (TDAS) CFTR |
510(k) |
Luminex Molecular Diagnostics |
15-Dec-2016 |
|
Chronic Myeloid Leukemia |
Quantidex qPCR BCR-ABL IS Kit |
De Novo |
Asuragen, Inc. |
22-Jul-2016 |
|
Non-Small Cell Lung Cancer |
Cobas EGFR Mutation Test v2 |
PMA |
Roche Molecular Systems, Inc. |
6-Jun-2016 |
|
Colorectal Cancer |
Epi ProColon® |
PMA |
Epigenomics AG |
12-April-2016 |
|
B-cell chronic lymphocytic leukemia |
VYSIS CLL FISH Probe Kit |
PMA |
Abbott Molecular Inc. |
11-Apr-2016 |
|
Aggressive Systemic Mastocytosi |
Kit D816V Assay |
HDE |
Arup Laboratories |
18-Dec-2015 |
|
Myelodysplastic syndrome / myeloproliferative disease |
Fluorescence in situ hybridization, platelet-derived growth factor receptor, beta polypeptide (pdgfrb), rearrangement |
HDE |
Arup Laboratories |
18-Dec-2015 |
|
Colorectal Cancer |
Cobas KRAS Mutation Test |
PMA |
Roche Molecular Systems, Inc. |
7-May-2015 |
|
Autosomal Recessive Carrier Screening |
23ANDME Personal Genome Service |
De Novo |
23andMe |
19-Feb-2015 |
|
Breast Cancer |
SPoT-Light HER2 CISH Kit |
PMA |
Invitrogen Corporation |
7-Jan-2015 |
Despite the recent FDA approvals and policy initiatives, there are various challenges that need to be addressed for personalized medicine to be successfully implemented. The FDA is still working to ensure the accuracy of Next Generation Sequence (NGS) tests, so that patients and clinicians can receive accurate and clinically meaningful test results. The vast amount of data obtained from one’s genetic material makes it difficult to draw meaning from genomic profiling of patients. Several genomic and proteomic related companies are partnering with players in other technologies to overcome these challenges. Partners include technology and information management companies, as well as academic institutions and hospitals. Table 2 presents some of the partnering companies/universities and the purpose of their collaborations from recent times.
Table 2: Collaborations in Companion Diagnostics
|
Collaborating Partners |
Purpose |
Date |
|
Akoya Biosciences & Precision for Medicine (formerly ApoCell) |
To advance immuno-oncology candidates in clinical trials using both tumor biopsies and liquid biopsies to generate data required for assessing drug efficacy and validation of companion diagnostics (CDx) |
|
|
MEDx (Suzhou) Translational Medicine & Lucence |
To pursue a strategic partnership in China to co-develop cancer-care tests that would benefit patients and pharmaceutical companies |
|
|
ArcherDX & Ayala Pharmaceuticals |
To develop companion diagnostic (CDx) tests targeting cancers bearing Notch activating mutations and fusions |
|
|
Adial Pharmaceuticals & Eurofins Scientific |
To study AD04, a genetically targeted therapeutic agent for the treatment of Alcohol Use Disorder |
|
|
Kiyatec & CarThera |
To advance innovation and improve treatments for patients diagnosed with glioblastoma |
|
|
Shriners Hospitals for Children & Genome Medical |
To offer high-quality genomic services and precision medicine for pediatric patients |
|
|
NEC Corporation & VAXIMM AG |
To develop novel personalized neoantigen cancer vaccines |
|
|
Promega & Merck |
To develop Microsatellite Instability (MSI) companion diagnostic for use with Keytruda |
|
|
Caris Life Sciences & Debiopharm |
To develop a companion diagnostic for an oncology drug being developed by Debiopharm |
|
|
Myriad & AstraZeneca & Merck |
To identify germline BRCA mutations in men who have metastatic castrate-resistant prostate (mCRPC) cancer |
|
|
Thermo Fisher & Eli Lilly |
To develop a companion diagnostic for LOXO-292, a cancer candidate |
|
|
Agilent & SomaLogic |
To drive biomarker discovery efforts as well as novel diagnostics and accelerated pharmaceutical development |
|
|
Agilent & NUS & NUH, Singapore |
To develop new methods of transforming clinical research into diagnostics |
|
|
Biocartis & Bristol-Myers Squibb |
To use the Idylla™ MSI test in connection with immuno-oncology therapies |
|
|
Qiagen & Illumina |
To accelerate the adoption of next-generation sequencing (NGS) in clinical decision-making |
Available treatment options for several conditions are ineffective, cause severe side effects, or result in treatment resistance. Medical professionals are optimistic that personalized treatment approaches would improve outcomes in such diseases. In spite of the FDA’s strides in creating draft guidance and other archives that concern a regulatory pathway for personalized medicine, uncertainty remains regarding regulations related to laboratory-developed tests for specific conditions. Proof of therapeutic outcomes for many conditions as well as, clinical and economic impacts of treatments are still pending. A set approach for obtaining this information has yet to surface. With international regulations, as well as collaborations and partnerships between companion diagnostic players, we might move closer to making personalized medicine a reality.
