Myriad to Seek FDA Approval of Diagnostic Test to Determine Lynparza Eligibility for mCRPC Patients

Myriad Genetics is filing an application with the U.S. Food and Drug Administration requesting the approval of its BRACAnalysis CDx — which identifies inherited BRCA mutations — as a companion diagnostic test for selecting metastatic castration-resistant prostate cancer (mCRPC) patients eligible for Lynparza (olaparib) treatment.

The announcement comes after promising results from the Phase 3 PROfound trial (NCT02987543), showing that Lynparza is significantly better than hormone therapy at delaying disease worsening or death in mCRPC patients with BRCA or ATM mutations.

“The PROfound trial confirmed the potential benefits of using biomarkers to help guide care for men with metastatic castration-resistant prostate cancer,” Johnathan Lancaster, chief medical officer of Myriad Genetics, said in a press release.

Lynparza is an anti-cancer agent known as a PARP inhibitor. These agents block an enzyme called poly (ADP-ribose) polymerase (PARP), which helps repair DNA. By blocking this process, PARP inhibitors keep cancer cells from repairing their damaged DNA, causing their death.

The treatment is approved for some ovarian and breast cancers, and appears to work particularly well in people with defects in their DNA repair mechanisms, who accumulate DNA errors faster than those with normal DNA repair.

In fact, three out of four Lynparza indications are exclusively for people with inherited BRCA mutations, the most common mutations in DNA repair pathways. For one such indication — first-line maintenance treatment for advanced ovarian cancer patients — patients are first examined with Myriad’s companion diagnostic test to confirm they have inherited BRCA mutations and are eligible for Lynparza treatment.

The PROfound study compared the efficacy and safety of Lynparza versus Xtandi (enzalutamide) or Zytiga (abiraterone) in mCRPC patients whose disease had progressed while on these newer hormone treatments.

Eligible patients also had a mutation in one of 15 genes involved in DNA repair. Myriad’s BRACAnalysis CDx was used to select patients with mutations in the BRCA1 or BRCA2 genes.

Earlier this month, Lynparza’s developers, AstraZeneca and Merck (known as MSD outside the U.S. and Canada), announced that the trial had met its primary goal, with Lynparza extending the time without disease progression or death in men with BRCA1, BRCA2, or ATM mutations, compared with standard hormone treatment.

These findings support the use of BRACAnalysis CDx to identify mCRPC patients more likely to respond to Lynparza.

“We congratulate AstraZeneca and Merck on the successful completion of the PROfound trial and look forward to expanding the population of people who can potentially benefit from testing with BRACAnalysis CDx,” said Nicole Lambert, president of Myriad Oncology. “Importantly, this study is another example of Myriad’s commitment to leverage our portfolio of tumor and germline [inherited] tests to develop and deliver precision medicine for people with cancer.”