ipsogen IDH1 RGQ PCR Kit

The ipsogen IDH1 RGQ PCR Kit is a qualitative real-time PCR assay for the detection of single nucleotide variants (SNVs) encoding five IDH1 mutations (R132C, R132H, R132G, R132S, and R132L). The assay uses genomic DNA extracted from fresh or frozen human whole blood (WB) or bone marrow aspirate (BMA) specimens collected in K2-EDTA tubes from patients with acute myeloid leukaemia (AML).

The test is intended to be used as a companion diagnostic device to aid clinicians in identifying AML patients who may be eligible for treatment with TIBSOVO (ivosidenib) based on the detection of an IDH1 mutation.

TIBSOVO may be administered in combination with azacitidine, in accordance with its approved indications. The test is not intended to guide treatment decisions for azacitidine.

For details on the performance, refer to the “Performance Characteristics” section of the ipsogen IDH1 RGQ PCR Kit Instructions for use.

Clinical performance: Diagnostic sensitivity and specificity¹

The ipsogen IDH1 RGQ PCR Kit (IDH1 Kit) was compared with a next generation sequencing (NGS) reference test, the Archer VariantPlex Core Myeloid panel (validated by ICON) in newly diagnosed AML patients (Table 1) (using both BMA and peripheral blood [PB] samples). The overall diagnostic sensitivity was 98.48% (Clopper-Pearson (Exact) Binomial 95% Confidence Interval (CI): (91.84%, 99.96%) and diagnostic specificity was 100% (95% CI: (96.11%, 100%) (Table 2).

Table1. ipsogen IDH1 RGQ PCR Kit vs reference test (ICON NGS) for newly diagnosed AML – Analysis for all mutations 

Table 2. Diagnostic sensitivity and specificity for newly diagnosed AML – Analysis for all mutations

The analysis of clinical performance was also performed on a per-mutation basis as presented in Table 3 and Table 4.

Table 3. ipsogen IDH1 RGQ PCR Kit vs reference test (ICON NGS) for newly diagnosed AML – Analysis per mutation

Table 4. Diagnostic sensitivity and specificity for newly diagnosed AML – Analysis per mutation

Clinical performance: Clinical utility/efficacy of the ipsogen IDH1 RGQ PCR Kit with TIBSOVO treatment in combination with azacitidine in newly diagnosed AML.¹

A clinical bridging study demonstrated that the PPA and NPA for the device in question vs the Abbott Realtime IDH1 device (used for enrolment for AG120-C-009) met the concordance requirements of PPA and NPA ≥95%. Furthermore, in newly diagnosed AML patients the clinical efficacy in terms of event free survival (EFS) and other clinical endpoints were in line with the summary results in the drug AG120-C-009 study report.

1. ipsogen IDH1 RGQ PCR Kit Instructions for use.

The ipsogen IDH1 RGQ PCR Kit is based on the detection by selective amplification of five IDH1 mutations in genomic DNA (gDNA) extracted from whole blood or bone marrow aspirate (BMA) specimens. Allele-specific technology allows accurate and highly reproducible detection of target IDH1 mutations, based on the use of specific forward and reverse primer and probe sets; mutation-specific primers bind selectively to the target DNA, which promotes extension and amplification in the PCR reaction.

Result reporting is fully automated. If both the run controls and the sample results are valid, and assay target amplification is below the pre-determined cutoff threshold, the report will display the IDH1 mutation(s) detected in each sample.

The simple and straightforward testing workflow begins with manual DNA extraction from either fresh or frozen human whole blood or bone marrow aspirate specimens collected in K2-EDTA tubes using the QIAamp DSP DNA Blood Mini Kit. This is followed by sensitive real-time PCR on the Rotor-Gene Q MDx 5plex HRM instrument. Rotor-Gene AssayManager (RGAM) software v2.1 or later with the Rotor-Gene AssayManager Gamma Plug-in v1.0 or later and the ipsogen IDH1 RGQ PCR Kit Assay Profile rapidly and accurately determine mutations. The results are reported, informing the system operator if one or more of the five mutations detected by the kit are present. The assay can be completed in ~8 hours, providing same-day results.

The ipsogen IDH1 RGQ PCR Kit enables qualitative detection of single nucleotide variants (SNVs) encoding five IDH1 mutations (R132C, R132H, R132G, R132S and R132L) for in vitro diagnostic use. The kit is intended to discriminate between IDH1 mutation-negative (wild-type) and IDH1 mutation-positive patient DNA.

The ipsogen IDH1 RGQ PCR Kit is a clinically validated IVD PCR test intended to aid in the identification of AML patients for treatment with TIBSOVO (ivosidenib).