Originally published June 29.
By Turna Ray
Amid economic pressures dragging at Myriad Genetics' BRACAnalysis revenues, the diagnostics developer has recently been emphasizing to investors its strategic focus on companion diagnostics development with big pharma.
Traditionally, Myriad has developed tests that gauge patients' cancer risk and likelihood of responding to certain chemotherapeutics. However, during a call with analysts in March, Myriad executives acknowledged that during a period when doctors' visits had declined by 20 percent, revenues from its BRACAnalysis test were also lower than anticipated. Simultaneously, in an effort to highlight the various revenue sources for the company beyond the money coming in from its flagship BRCA test, Myriad execs discussed the firm's growing focus on companion diagnostics development with large pharmaceutical partners (PGx Reporter 03/10/10).
Since then, Myriad has been presenting itself as a serious contender in the companion diagnostics market. "Myriad is very much a player in the field of companion diagnostics," Myriad Genetics CEO Peter Meldrum told investors at the Goldman Sachs annual global healthcare conference earlier this month.
In his presentation, which was webcast, Meldrum focused on Rx/Dx collaborations with AstraZeneca and Abbott, pharmaceutical companies that are developing a class of oncologics called PARP inhibitors and are using Myriad's BRACAnalaysis test to stratify patients in clinical trials based on their BRCA gene mutation status.
The PARP1 enzyme and the BRCA gene work in concert to repair DNA damage, enabling the tumor to survive. However, in patients with mutations in the BRCA gene, when PARP inhibitors destroy the PARP1 enzyme, the tumor is unable to repair DNA damage and dies.
Since the BRACAnalysis test can identify which patients have BRCA1/2 mutations and therefore would respond to PARP inhibitors, the test is being used by AstraZeneca in the development of olaparib in breast and ovarian cancer and by Abbott to stratify breast cancer patients in clinical trials for veliparib. At the American Society of Clinical Oncology's annual meeting, both firms presented studies that demonstrate this link between BRCA mutations and response to PARP inhibitors.
In addition to developing companion diagnostics for PARP inhibitors, Myriad is also working with "four major pharmaceutical companies" who are using its Prezeon test to stratify patients for clinical trials involving another class of oncologics, PTEN inhibitors.
As a major antioncogene, the PTEN gene is an important player in cell signaling pathways that are targeted by EGFR inhibitors and mTOR inhibitors. Myriad's Prezeon gauges the loss of PTEN function, which is associated with more aggressive cancer and poorer survival in patients.
Meldrum reminded investors that the company has strong intellectual property protection around its companion diagnostics for PARP and PTEN inhibitors.
Several studies presented by AstraZeneca and Abbott at ASCO's annual meeting shed light on the development of investigational PARP inhibitors with the aid of Myriad's BRACAnalysis test.
Myriad's test is being used to stratify patients in a Phase II study with AstraZeneca's olaparib. At ASCO, researchers from AstraZeneca, the UK's Royal Marsden NHS Foundation Trust, and others presented data from a preliminary study showing evidence that patients with BRCA1/2-deficient ovarian cancer are responsive to taxane or platinum-based chemotherapy after treatment with olaparib.
In another study presented at ASCO, researchers from AstraZeneca and several Canadian institutions reported data from "the first trial demonstrating significant evidence of single-agent activity of olaparib in women with high grade serous ovarian cancer." The researchers are planning to report data from an updated translational study in BRCA-positive and BRCA-negative tumors.
"If the AstraZeneca drug goes through the FDA and is approved we would actually appear on the drug label," Meldrum told investors at the Goldman Sachs meeting. According to AstraZeneca's website, new drug application filing dates for olaparib are slated for 2012 in BRCA-mutated breast cancer and in 2014 for serious ovarian cancer.
The US Food and Drug Administration has made it clear that for tests to predict drug response, if the sponsor wants the test listed by name in the drug's label, the firm will have to submit that test for premarket approval by the agency. The BRACAnalysis test is a laboratory-developed test analyzed in Myriad's CLIA-certified laboratory, and has not garnered 510(k) clearance or a PMA from the FDA.
PGx Reporter received no response to an e-mail sent to Myriad asking whether the company intended to submit the test for FDA approval if AstraZeneca's olaparib advanced successfully through clinical trials.
Meanwhile, Abbott's PARP inhibitor is ABT-888, or veliparib, on which the company presented several abstracts at ASCO.
In one abstract on a Phase II trial, researchers from Massachusetts General Hospital, Abbott, and others concluded that 24 out of 41 breast cancer patients responded to combination treatment with veliparib and temozolomide at the time the data was submitted to ASCO. "Exploratory correlative studies including BRCA mutation analysis are underway to determine predictors of response," the researchers wrote in the abstract. They additionally note that clinical activity seen in this Phase II trial is not likely due to veliparib alone but rather to the combination treatment. "Veliparib and TMZ may be a promising new strategy in metastatic breast cancer," the researchers stated.
With regard to Myriad's companion test development for PTEN inhibitors, little is known. However, Meldrum again emphasized that if these drugs "were to be approved by the FDA, then PTEN would actually be on the drug label, and the label would say [the drug] was appropriate for individuals who have normal functioning PTEN status."
In terms of Prezeon's role as a companion test for PTEN inhibitors, Meldrum's comments make no mention of the test itself being included in the label, suggesting perhaps that the company plans to keep marketing it as an LDT for the time being.