Clinical laboratory managers and pathologists can expect more companion diagnostics in responses to advances in molecular knowledge about various diseases
Recently, the Food and Drug Administration (FDA) cleared two products for market, one of which may be of particular interest to anatomic pathologists. The first product is a therapeutic drug for the treatment of late-stage skin cancer. The second product is a companion clinical laboratory test that will be used to identify skin cancer patients most likely to benefit from this new drug.
This development is attracting attention by experts watching the molecular diagnostics marketplace. That’s because both products were developed by the same company on a tight timeline and this process is likely to be much studied by other pharma companies and genetic test developers.
The company that developed the new drug and its companion diagnostic test is Roche Holdings AG (OTCQX: RHHBY). In its press release about the FDA’s decisions, the company simultaneously announced market clearance of the drug Zelboraf (vemurafenib) and the approval of the companion diagnostic, the cobas 4800 BRAF V600 Mutation Test.
Zelboraf will only be used in the treatment of those patients with inoperable or metastatic melanoma who have tested positive for the BRAF V600E mutation as determined by an FDA-approved test, the release stated. Almost 50% of metastatic melanoma patients have the mutation.
In the press release, Hal Barron, M.D., FACC, Chief Medical Officer and Head, Global Product Development at Roche, stated that the approval “marks a major step forward in personalizing the treatment of metastatic melanoma.”
FDA Fast-tracks Promising Molecular Diagnostic Tests
Vemurafenib was reviewed under the FDA’s priority review program. The program provides for an expedited six-month review of drugs that may offer major advances in treatment or that provide a treatment when no adequate therapy exists, an FDA press release stated. Vemurafenib and the companion BRAF V600E test were approved ahead of their respective October 28, 2011 and November 12, 2011 goal dates.
In his comments, Barron had pointed out that patients with metastatic melanoma have a poor prognosis and limited treatment options. “If there is a group that a drug works really well in, there is some urgency getting it to them,” added Robert Temple, M.D., Director, Office of Medical Policy at FDA’s Center for Drug Evaluation and Research. Temple explained that it is easier for regulators to approve experimental therapies that show a strong benefit in select patients and allows for a smaller clinical trial population to evidence efficacy.
The mutated gene called BRAF is the subject of much clinical research. This mutated gene drives the proliferation of cancer cells, as reported by The Wall Street Journal online. Vemurafenib stops that process.
In clinical trials, the drug decreased the risk of death among the subset of patients by 64%, compared with people using the standard chemotherapy, the Journal piece noted. Almost 50% of the patients taking the pills saw their tumors shrink compared with 5.5% who received chemotherapy.
That press release describes the cobas 4800 BRAF V600 Mutation Test as an investigational, polymerase chain reaction-based companion diagnostic. The company developed the test to identify people whose tumors carry the BRAF V600 mutation.
The speedy action by the FDA to clear for market both the therapeutic drug and the companion diagnostic test signals U.S. regulators’ enthusiasm for such targeted therapies, the Journal writer said. Clinical laboratory managers and pathologists should note that reaction by regulators. It is a response to the improved prognosis for patients that is combined with dramatic decrease in cost of treatment afforded by such targeted diagnostics as vemurafenib.
The genetic test identifying patients with the BRAF mutation will cost between $120 and $150, according to Roche. The typical six-month course of Zelboraf carries a price tag estimated at $56,400. Rival treatments can cost as much as $120,000, the Journal noted.
Drugs, Companion Diagnostics Are Front Edge of Personalized Medicine
“[A]pproval of Zelboraf and the cobas test is a great example of how companion diagnostics can be developed and used to ensure patients are exposed to highly effective, more personalized therapies in a safe manner,” said Alberto Gutierrez, Ph.D., Director, Office of In Vitro Diagnostic Device Evaluation and Safety in the FDA’s Center for Devices and Radiological Health, in an FDA press release.
Your Dark Daily editor, Robert Michel, attended the recent Personalized Medicine World Conference, held in Silicon Valley. (See Dark Daily, “Changing Role for Pathology and Clinical Laboratory Testing Discussed at Personalized Medicine World Conference in Silicon Valley”.) In his story covering the conference, Michel acknowledged that the handful of therapeutic drugs that come with a companion diagnostic assay, such as vemurafenib and the cobas test, may be considered the leading edge of personalized medicine routinely used in clinical practice today.
Clinical laboratory managers and pathologists can expect to see more opportunities for personalized medicine products and services with the expected advances in genetic and molecular knowledge about different diseases.
—Pamela Scherer McLeod