Development of Diagnostic Tests for Targeted Therapies Faces Multiple Challenges

Targeted therapies are treatments aimed at specific biomarkers, such as genetic mutations, or overexpressed proteins. Tests that detect the targeted biomarker are needed to determine whether a patient would benefit from the treatment. The FDA offers an approval pathway for such tests, so-called “companion diagnostics” (CoDx), which requires that the test be evaluated alongside the drug in clinical trials. However, testing laboratories can also develop their own tests. These “laboratory-developed tests” (LDTs) are not currently regulated by the FDA. Development of LDTs is therefore much cheaper and faster (making CoDx comparatively less economically viable), but provides less evidence that these test are indeed effective. Moreover, LDTs can be designed to test for many different biomarkers, thus making more efficient use of limited biopsy tissue, while CoDx usually only test for the one biomarker relevant for their companion drug. A recent article calls for test developers, pharmaceutical companies, insurers, and the FDA to collaborate in resolving these issues.


Development of Diagnostic Tests for Targeted Therapies Faces Multiple Challenges

Targeted therapies are treatments aimed at specific biomarkers, such as genetic mutations, or overexpressed proteins. Tests that detect the targeted biomarker are needed to determine whether a patient would benefit from the treatment. The FDA offers an approval pathway for such tests, so-called “companion diagnostics” (CoDx), which requires that the test be evaluated alongside the drug in clinical trials. However, testing laboratories can also develop their own tests. These “laboratory-developed tests” (LDTs) are not currently regulated by the FDA. Development of LDTs is therefore much cheaper and faster (making CoDx comparatively less economically viable), but provides less evidence that these test are indeed effective. Moreover, LDTs can be designed to test for many different biomarkers, thus making more efficient use of limited biopsy tissue, while CoDx usually only test for the one biomarker relevant for their companion drug. A recent article calls for test developers, pharmaceutical companies, insurers, and the FDA to collaborate in resolving these issues.


Development of Diagnostic Tests for Targeted Therapies Faces Multiple Challenges

Targeted therapies are treatments aimed at specific biomarkers, such as genetic mutations, or overexpressed proteins. Tests that detect the targeted biomarker are needed to determine whether a patient would benefit from the treatment. The FDA offers an approval pathway for such tests, so-called “companion diagnostics” (CoDx), which requires that the test be evaluated alongside the drug in clinical trials. However, testing laboratories can also develop their own tests. These “laboratory-developed tests” (LDTs) are not currently regulated by the FDA. Development of LDTs is therefore much cheaper and faster (making CoDx comparatively less economically viable), but provides less evidence that these test are indeed effective. Moreover, LDTs can be designed to test for many different biomarkers, thus making more efficient use of limited biopsy tissue, while CoDx usually only test for the one biomarker relevant for their companion drug. A recent article calls for test developers, pharmaceutical companies, insurers, and the FDA to collaborate in resolving these issues.


Gilotrif to Be Commercially Available in the U.S. Soon

Afatinib (Gilotrif), a new drug for the treatment of some lung cancers, will become commercially available in the U.S. beginning the week of September 2. Gilotrif is approved as a first-line treatment for patients with advanced non-small cell lung cancer (NSCLC) who have certain mutations in the EGFR gene. A companion diagnostic, the therascreen EGFR RGQ PCR Kit, can detect these specific EGFR mutations, so-called exon 19 deletions or exon 21 (L858R) substitutions. The makers of the drug will offer a patient support program to provide financial and other support to help patients who might otherwise not have access to Gilotrif.


Afatinib is FDA-Approved: What It Means For NSCLC Patients


On July 12, the FDA announced that it had approved the targeted therapy afatinib (Gilotrif) for the treatment of metastatic non-small cell lung cancer (NSCLC) with mutations in the epidermal growth factor receptor (EGFR) gene.

EGFR mutations occur in about 10 to 15 percent of all NSCLC patients. The overexpression of the EGFR protein caused by the mutation leads to rapid cell division in tumors. Prior to the approval of afatinib, patients in the United States could only take erlotinib (Tarceva) to combat the EGFR mutation. The third major drug available to treat EGFR-mutated tumors, gefitinib (Iressa) has not yet been approved by the United States but is readily available in many other countries. Erlotinib has consistently outperformed gefitinib, so its lack of availability in the U.S. is no huge loss. Continue reading…


FDA Approves Afatinib/Gilotrif for Lung Cancer Treatment

Based on the positive results of a recent clinical trial, the FDA approved afatinib for first-line treatment of patients with late-stage, non-small cell lung cancer (NSCLC) who have a mutation in the EGFR gene. The drug, which will be marketed under the name Gilotrif, is specifically intended for patients with two particular EGFR mutations: exon 19 deletion and exon 21 L858R substitution. The FDA also approved the therascreen EGFR RGQ PCR Kit, a companion diagnostic used to test for EGFR mutations. Afatinib differs from other EGFR inhibitors like erlotinib (Tarceva) and gefitinib (Iressa) in that it irreversibly destroys the EGFR protein, instead of just reversibly blocking it, and also inhibits several other related proteins.


FDA Approves Expanded Use and Companion Diagnostic for Tarceva

The FDA has approved the use of erlotinib (Tarceva) as a first-line treatment for patients with advanced non-small cell lung cancer (NSCLC) who have a mutation in the EGFR gene. Tarceva, a tyrosine kinase inhibitor (TKI) that inhibits EGFR, had already been approved for patients with advanced NSCLC as a second- or later-line treatment if at least one chemotherapy regimen had failed, or as maintenance treatment if their disease had not progressed after four cycles of chemotherapy. At the same time, the FDA approved, for the first time, a test for EGFR mutations, the cobas EGFR Mutation test. The test enables doctors to identify which patients have EGFR mutations and are therefore candidates for first-line treatment with Tarceva, making it a so-called ‘companion diagnostic’ for Tarceva.