Having Biomarker Data Early
Vemurafenib stands apart from other cancer drugs with companion tests because knowledge of specific mutations affecting drug response was available early in the drug’s development cycle. Dr. Koch explained that while there are multiple examples of cancer drugs with specific biomarker tests that characterize the diseases, knowledge of specific mutations affecting drug response became available after the drugs were developed. “This substantially changes the market,” Dr. Koch said.
Drugs approved along with a companion diagnostic include Eli Lilly’s Erbitux and Amgen’s Vectibix, both anti-epidermal growth factor receptor (EGFR) antibodies. The original companion diagnostic, EGFR pharmDx, which detected EGRF status in patients, was developed by partnering with DAKO.
Evidence that KRAS mutation status would affect how subjects responded to anti-EGFR treatments became apparent only after clinical trials that formed the basis of NDA and MAA submissions were completed. Amgen and Imclone analyzed the existing information and found that about 43% of patients, those with KRAS mutations, did not respond to the EGRF inhibitors.
“Therefore, if you had a diagnostic test for the KRAS mutations, you would have 40% of patients who wouldn’t get the therapy but who would have been treated prior to that knowledge.”
But, Dr. Koch said, many drugs are evolving along the lines of BRAF, “where an activating mutation in an oncogene makes sense to target specifically or knowledge of a pathway downstream portends failure for the drug and suggests other development strategies.”
Amgen has bolstered work on identifying biomarkers that will allow the company to predict which patients will or won’t respond to a given drug. Generally the company identifies a diagnostic company with appropriate expertise to partner with depending on the type of test needed.
“We believe it’s an essential part of the drug development process,” Dr. Reese told GEN. “Every product we put into humans has a biomarker team formed typically one to two years before the first patient is dosed with a drug.” He explained that the teams have two mandates. “One is to potentially develop pharmacodynamic biomarkers that tell you whether the drug is doing what you think it should be doing. For example, if you are targeting a receptor in cancer, is your drug getting in at an appropriate level and shutting the receptor off?
“The second mandate of that team is to identify those patients likely to respond or not respond to the therapy. Our goal is to get the right drug to the right patient as early in the process as possible, starting that effort even with preclinical work.”
Dr. Reese explained that what potentially differentiates Amgen from companies developing companion diagnostics for their drug candidates is “the scale of the effort and the formation of cross-functional teams with the sole mandate of biomarker development.”