Myriad Genetics Inc.'s strategy to remake the growth prospects for its BRACAnalysis gene testing service took a step in the right direction with the Dec. 19 FDA approval of its BRACAnalysis CDx assay as a companion diagnostic to AstraZeneca PLC’s ovarian cancer drug Lynparza (olaparib). The approval is also an important milestone in FDA's oversight of laboratory developed tests.

It is Myriad's first companion diagnostic approval for the BRCA1/2 genetic assay, resulting from an ongoing collaboration with AstraZeneca. [See Deal] Myriad plans to make companion diagnostics a central component of its business moving forward as it diversifies its offerings beyond hereditary breast and ovarian testing.

The company is partnering with several drug makers to develop different companion diagnostic indications for BRACAnalysis CDx and new companion diagnostic assays. (See [A#01131223018].)

A Leg Up

The recent approval gives Myriad's test a leg up on the growing cadre of BRCA1/2 assay competitors that have surfaced since Myriad's gene patents were invalidated by the Supreme Court in 2013. First of all, it does so because the assay is specifically referenced in Lynparza's drug label, via a hyperlink, making it the likely choice for a physician considering use of the medication. FDA approved Lynparza for patients with germline mutations in BRCA1/2 advanced ovarian cancer who have had three or more attempts of chemotherapy. The therapy is a PARP inhibitor, one of an emerging class of investigational cancer drugs.

This marks the first time that FDA has approved a laboratory-developed test as a companion diagnostic, and the first time an LDT was approved via the PMA process.

Additionally, although the BRACAnalysis platform has been available for many years, this is the first time it or any BRCA1/2 system has been approved by FDA, providing important validation for the company's test.

"Myriad has proven its ability to navigate a rigorous FDA regulatory approval process that included a comprehensive review of our DNA sequencing, large rearrangement detection and variant interpretation processes," said Mark Capone, the company's president. "Patients can be confident their BRACAnalysis CDx test results from Myriad are highly accurate."

Myriad will offer BRACAnalysis CDx as a service from its Salt Lake City CLIA-complex laboratory, as it has for the non-companion-diagnostic version of the assay for some time. While FDA has previously cleared a handful of laboratory-developed tests (LDT), this marks the first time that FDA has approved one as a companion diagnostic. The other 19 companion diagnostics approved by the agency are tests that are packaged and sold to labs as kits.

The BRACAnalysis CDx is also the first LDT approved via the PMA process and is a sign of things to come as FDA moves to bring these sorts of test service offerings into its regulatory fold. The agency recently proposed a phased-in regulatory framework for LDTs that would put other makers of BRCA1/2 assays near the front of the line to gain FDA approval to market their tests if and when the framework takes effect. (See Also see "FDA Plan To Regulate LDTs Includes Long Phase-In, Unmet-Need Exceptions" - Medtech Insight, 31 July, 2014..)

Label Narrower Than Anticipated

The Lynparza/BRACAnalysis CDx approval came slightly earlier than expected; Myriad had been anticipating a decision in early January.

But while the news marks an important milestone and “should strengthen Myriad’s competitive position,” according to Jefferies analyst Brandon Couillard, he points out that the approved Lynparza labeling included a narrower patient population than anticipated.

“Specifically, Lynparza's drug label is for use in the fourth-line setting versus AstraZeneca’s initial submission for use as a ‘maintenance therapy’ (given to patients between chemo treatments),” the analyst wrote in a research note. “We expect the eligible US ovarian cancer patient population may be slightly smaller than initial expectations.”

Lynparza was also approved recently in Europe as a maintenance therapy for ovarian cancer patients with germline and/or somatic BRCA mutations. But Myriad's test will not have the same official validation in that region as it does in the U.S.

“Due to different regulatory structures for companion diagnostics in the EU versus U.S., the [European Medicines Agency] does not have the authority to approve companion diagnostics, though it does require that validated tests be available upon drug launch,” Couillard wrote. He noted that Myriad will compete there “with at least two other competitors (including Foundation Medicine) with its main competitive advantages being turnaround time and accuracy.”

Diversifying Focus

Increased market competition is a principle driver of Myriad's companion diagnostics strategy. The 2013 Supreme Court ruling invalidating the company's gene patents ushered in the introduction of BRCA assays for assessing risk of hereditary breast and ovarian cancer from a range of companies, including very large players such as Quest Diagnostics Inc. and multiple smaller labs. (See Also see "Diagnostic Companies Rush To Test Formerly Off-Limit Genes" - Medtech Insight, 24 June, 2013..)

Lawsuits quickly followed and Myriad says it maintains a vigorous focus on its hereditary cancer testing market. But the company is looking ahead into two primary directions to stay ahead of the pack. One direction is the development of its 25-gene myRisk Hereditary Cancer panel, which it hopes will ultimately replace the standalone BRCA1/2 assays in the market for risk screening. (See Also see "ASCO 2014: Oncology Companion Diagnostics Market Poised For Growth" - Medtech Insight, 16 July, 2014..) Second, it is targeting companion diagnostics.

Myriad says it is working to incorporate its BRACAnalysis system with five of the six pharmaceutical companies that are actively developing PARP inhibitors. It is also developing the test as a companion diagnostic for other solid tumor types.

In addition to AstraZeneca, which Myriad is also working with on a breast cancer indication for Lynparza, Myriad has also disclosed companion diagnostics collaborations with BioMarin Pharmaceutical Inc., AbbVie Inc., Tesaro Inc., Teva Pharmaceutical Industries Ltd., Janssen Pharmaceuticals Inc., and PharmaMar SA.

Many projects with these companies involve BRACAnalysis Dx, but Myriad is working with some of the drug firms to develop another assay, myChoice HRD (homologous recombination deficient), as a companion diagnostic.

Positive data was presented for myChoice HRD in early December at the San Antonio Breast Cancer Symposium for aiding treatment of early-stage triple-negative breast cancer with platinum drug chemotherapy. Myriad hopes to launch the test as an LDT sometime in 2015, with limited availability beginning in June or July.

Myriad Enters Companion Diagnostics Field With An FDA First

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