Originally published March 27.
Genoptix, the medical laboratory within Novartis's molecular diagnostics unit, has launched a targeted sequencing-based test for mutations in BRAF, NRAS, and c-KIT to help physicians tailor treatment for metastatic melanoma patients.
The NexCourse Melanoma sequencing profile, offered through Genoptix's CLIA lab, is the company's first sequencing-based test service and is already being ordered by physicians, according to the firm. Genoptix's President Tina Nova declined to provide details on how the test is being used so far but did tell PGx Reporter in an e-mail that the panel is not being used to place patients into clinical trials for Novartis drugs.
The company sees the service as a tool to help inform treatment decisions for patients with metastatic melanoma by screening for clinically relevant mutations in three genes associated with different prognoses and potential responses to targeted treatments.
However, the NGS profile is "not intended as a test for any specific drugs;" is not linked to any drugs in Novartis' pipeline targeting BRAF, NRAS or c-KIT mutations; and the company is not using the NGS profile to place patients into clinical trials involving drugs in development, "nor do we have any plans to do so," Nova wrote.
And although the service will assess BRAF mutations — including V600E and V600K mutations — it is not intended to guide treatment with Roche’s Zelboraf, which is indicated for BRAF V600E mutation-positive metastatic melanoma. The US Food and Drug Administration approved the drug in August alongside Roche's internally developed companion test, the Cobas 4800 BRAF V600 Mutation Test.
"Our focus in Genoptix is on providing physicians with the most relevant clinical information. We believe that NGS technology is going to factor heavily in the diagnosis and treatment of patients in the future," Nova said.
Novartis acquired Genoptix in January 2011 and the business falls within Novartis Molecular Diagnostics, a unit formed around three years ago. The primary focus of the Novartis MDx business is companion diagnostics, but the company is also pursuing a "complementary diagnostics" strategy, which includes tests that don't require extensive coordination between drug and diagnostic development arms or simultaneous drug/test approval by the FDA (PGx Reporter 12/7/2011).
Nova did not detail Genoptix’s hopes for the testing service beyond offering a more comprehensive test than currently available single-gene assays to “help physicians tailor treatment for each patient.”
"The NGS profile provides us with a much more comprehensive picture of the tumor than with assays that target specific point mutations,” she said.
According to Nova, the price of the service is "dependent on the elements of the diagnostic profile selected by the physician," meaning physicians can specify which mutations they want to target. Nova wrote that a complete profile is listed at $2,600, which is “of comparable cost to other commercially available high-value diagnostic tests."
She said Genoptix is “actively working with payors to demonstrate the value of next-generation testing and to discuss favorable reimbursement rates,” and is “optimistic that the value of next-generation testing will be recognized by payors."
While the company will report mutations of unknown clinical significance, Nova stressed that the service is intended to provide physicians with actionable information. However, she did not elaborate on how Genoptix sees the “clinically relevant” mutations the test identifies actually impacting treatment.
Genoptix currently offers Roche's FDA-approved BRAF V600E test to identify patients likely to benefit from Roche’s Zelboraf. Nova suggested that the broader NGS melanoma test might best be used on patients negative for BRAF V600E.
"Ultimately, it is the physician’s decision to choose the appropriate test for his or her patient," Nova wrote. “However, we believe our NGS melanoma profile may be particularly useful when the Cobas BRAF V600E result is negative and the patient has limited treatment options."
Zelboraf's label states that an "FDA-approved" BRAF V600E test is required for determining which patients will respond to the drug, but the agency has not issued treatment recommendations for other BRAF mutations.
The Genoptix NGS service, like other sequencing-based tests offered through CLIA labs, is considered a lab-developed test and is therefore not subject to FDA scrutiny until the agency issues guidelines on its plans to regulate LDTs. The company joins a number of labs offering LDTs for BRAF who are free to do so until the FDA finalizes its LDT oversight strategy (PGx Reporter 9/28/2011).
Even though Genoptix claims that its test is not intended to aid its parent company's drug development plans, Novartis currently has several drugs in development potentially targeting the same melanoma PGx populations that the test is designed to identify.
One, RAF265, is a compound in phase I that has shown promise in reducing tumors in BRAF-mutated mice. Another, MEK162, is currently in phase I trials for melanoma and other cancers in patients with NRAS and BRAF mutations. The company is also studying the use of nilotinib — currently marketed as a chronic myeloid leukemia drug — for melanoma patients with c-KIT mutations in a Phase II trial that started in 2010.
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