Latest Thinking

Personalized medicine for ‘niche’ populations

February 1, 2013

Shazia Syed, ACPR., BSc.Phm
Source: Perspective Winter 2013 – by TELUS Health

Our previous article, “Personalized Medicines – A fruitful pharma trend with significant ramifications…,” discussed the rapidly progressing trend of personalized healthcare. Several new, expensive medications, targeted at niche populations with specific genetic mutations leading to disease development, have come to market in the past year. These drugs have also come to market with an accompanying diagnostic test, capable of identifying patients who are suitable candidates for the therapy. With the anticipated continued launch of targeted therapies co-marketed with specific diagnostic tests in the future—we will provide a couple of examples and a high level overview of the regulatory process for these diagnostic tests in Canada.

Zelboraf, an oral cancer drug for metastatic melanoma, and Xalkori, for non-small cell lung cancer (NSCLC), are two examples. Zelboraf was co-developed in clinical trials with a diagnostic test to identify patients with a positive mutation in the BRAF V600 gene— the cobas® 4800 BRAF V600 Test—with the rationale that mutations in BRAF (V600E mutations) cause the protein to be locked “on,” leading to constant growth signals that can contribute to cancer development. The mutant BRAF protein, including BRAF V600E, is found in approximately half of melanomas. The drug Zelboraf is thought to work by targeting and suppressing cells with the mutated BRAF protein, thereby preventing the cells from growing. By identifying patients with the specific mutation that has caused the cancer, patients have a higher probability of responding to the drug. Roche is the manufacturer of the drug and is also (Roche Diagnostics) the manufacturer of the cobas® 4800 BRAF V600 Test. The manufacturer of the drug is not necessarily the manufacturer of the accompanying diagnostic test as is the case for Pfizer’s drug Xalkori. Abbott, a separate manufacturer, has released the Vysis® ALK Break Apart FISH Probe Kit as the companion diagnostic test. The Vysis® ALK Break Apart FISH Probe Kit is intended to detect rearrangements involving the ALK gene which, when they occur, lead to the expression of cancer causing fusion proteins. The formation of ALK fusion proteins results in activation and dysregulation of the gene’s expression and signaling which can contribute to increased cell proliferation and survival in tumors expressing these proteins. Xalkori (Crizotinib) is a molecule that blocks the ALK receptor. Again, identifying patients with this particular gene expression ensures the use of the drug in those most likely to have the best clinical response.

The two tests above came about as the result of pharmacogenomics (PGx) which, according to Health Canada, is defined as “the study of variations of our genetics (DNA and RNA characteristics) as related to drug response.”i Once the relevant genes were identified, and the methods to identify them had been refined, the process was developed into a Pharmacogenomic Test. Pharmacogenomic tests must be licensed for sale in Canada or authorized by Health Canada for investigational testing if the test results are to be used for diagnostic purposes / patient management, or are to be submitted to Health Canada in support of a clinical trial application or drug submission. In the case of the two profiled pharmacogenomic tests, both are used to support a therapeutic decision (e.g. the choice of a drug) and are licensed for use in Canada.

Despite being used to identify those patients who will respond to drugs, the companion diagnostic tests noted above are not classified as drugs; they are classified as medical devices. According to Health Canada, the term “medical device” covers a wide range of products used in the treatment, mitigation, diagnosis or prevention of a disease or abnormal physical condition.ii

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