Myriad Genetics said today it will pursue FDA authorization of its BRACAnalysis CDx test as a companion diagnostic for the AstraZeneca/Merck & Co. co-marketed drug Lynparza (olaparib) in metastatic castration-resistant prostate cancer (mCRPC) patients with germline mutations of the BRCA gene.
Myriad said its decision to file a supplementary Premarket Approval Application (sPMA) for BRACAnalysis CDx followed the successful outcome of the Phase III PROfound trial (NCT02987543). AstraZeneca and Merck reported meeting the study’s primary endpoint of significantly increasing the time patients selected for BRCA1/2 or ATM mutations lived without radiographic disease progression vs. standard of care treatment.
The trial showed that men with mCRPC who tested positive for germline and somatic mutations in homologous recombination repair genes benefited from treatment with Lynparza, a poly ADP-ribose polymerase (PARP) inhibitor indicated for forms of breast cancer and ovarian cancer.
The PROfound trial was designed to assess the efficacy and safety of Lynparza compared with the Astellas Pharma/Pfizer co-marketed Xtandi® (enzalutamide) or Janssen Biotech (Johnson & Johnson)’s Zytiga® (abiraterone acetate) in mCRPC patients who have failed prior treatment with a new hormonal agent and have homologous recombination repair gene mutations.
Topline results from PROfound showed a statistically significant and clinically meaningful improvement of radiographic progression-free survival (PFS) among patients who tested positive for mutations in homologous recombination repair genes and were treated with Lynparza, AstraZeneca and Merck said.
“The PROfound trial confirmed the potential benefits of using biomarkers to help guide care for men with metastatic castration-resistant prostate cancer,” Johnathan Lancaster, M.D., Ph.D., chief medical officer of Myriad Genetics, said in a statement.
Myriad also cited updated 2019 National Comprehensive Cancer Network (NCCN) Guidelines®, which state that germline BRCA mutations should be tested in all newly diagnosed men with NCCN high-risk, very high-risk, regional, or metastatic prostate cancer.
Myriad and AstraZeneca have collaborated in the development of Lynparza since 2007. BRACAnalysis CDx has received approvals in the U.S. and Japan in six indications—the earliest of which came in December 2014, when the FDA approved BRACAnalysis CDx as a companion diagnostic to identify patients with advanced ovarian cancer who are eligible for fourth-line treatment with Lynparza.
BRACAnalysis CDx is an in vitro diagnostic (IVD) device intended for qualitative detection and classification of variants in the protein coding regions and intron/exon boundaries of the BRCA1 and BRCA2 genes using genomic DNA obtained from whole blood specimens collected in EDTA.
Single nucleotide variants and small insertions and deletions (indels) are identified by PCR and Sanger sequencing. Large deletions and duplications in BRCA1 and BRCA2 are detected using multiplex PCR, Myriad said.
