In the Pipeline

Amid a continuing emphasis on targeted therapies, pharmaceutical companies have approximately 300 drugs in phase II or later-stage development for cancer treatment that are likely candidates for companion biomarker testing, industry estimates indicate.

And, 10% to 20% of oncology agents in phase III trials this decade are expected to be developed along with a biomarker test, according to the 2011 Medco Drug Trend Report, which the pharmacy benefits management company Medco Health Solutions Inc produced.

A prominent example of such tandem development is crizotinib, an oral anaplastic lymphoma kinase (ALK) inhibitor targeted to ALK-positive non-small cell lung cancer (NSCLC). Pfizer Inc is seeking FDA approval for the drug through the priority review program while partnering with Abbott Molecular to develop a screening test to detect mutations in the ALK gene. Abbott has filed with the FDA for premarket approval of a test using fluorescence in situ hybridization technology to detect rearrangement of the gene’s 2p23 chromosome.

Likewise, the development of vemurafenib (RG7204, PLX4032) as a treatment for metastatic melanoma is moving through regulatory agencies in the United States and in Europe at the same time as a diagnostic test for positive mutations in the BRAF V600 gene, which the drug inhibits. Genentech, a member of the Roche Group, has submitted a new drug application to the FDA. Roche is pursuing approvals on both continents for the cobas 4800 BRAF V600 Mutation Test. Another ripe area of drug development concerns the influence of epidermal growth factor receptor (EGFR) in tumors. Roche is discussing a regulatory submission with the FDA to extend the use of erlotinib (Tarceva) to first-line treatment of patients with advanced NSCLC whose tumors test positive for the EGFR-activating mutation. The company has said a companion diagnostic would be included in the filing.

Afatinib (BIBW 2992) is a next-generation inhibitor of the erbB family of receptor tyrosine kinases, specifically EGFR and HER2, that is in late-stage development in several solid tumors including advanced NSCLC and breast cancer. Boehringer Ingelheim Pharmaceuticals, Inc has partnered with QIAGEN to develop a real-time polymerase chain reaction assay companion diagnostic to help identify patients whose tumors are EGFRmutation positive.

With abiraterone acetate (Zytiga), researchers are pursuing a different type of biomarker: circulating tumor cells (CTCs). Data presented at the American Society of Clinical Oncology meeting in June indicate CTCs measured through blood samples of patients with metastatic castrate-resistant prostate cancer served as a predictive marker for survival. Janssen Biotech, Inc, a Johnson & Johnson company, manufactures the drug.