Companion diagnostics are an emerging area of healthcare that offers patients a more personalized form of treatment for their disease. In a recent article on Xconomy titled “Companion Diagnostics for Cancer Drugs Advancing Personalized Medicine,” they state that “According to a study published in July 2011 by Joshua Cohen at the Tufts Center for the Study of Drug Development in Boston, less than one percent of drugs available in the U.S.—most of them cancer drugs—have a companion diagnostic.” While that number seems small the interest in companion diagnostics is growing, particularly in cancer where mutations indicate much about the disease, but also in neurology for Alzheimer’s disease, HIV therapies and several other areas.

The Food and Drug Administration (FDA) has also made their position on companion diagnostics clear in the Draft Guidance for Industry and Food and Drug Administration Staff – In Vitro Companion Diagnostic Devices issued in July 2011 in which they expressed a desire for companion diagnostics and the drugs they are linked with to be approved together. This makes the timing of drug development coupled with diagnostic development more of a challenge, but it also makes the clinical data stronger and ensures that there is good support and likelihood of reimbursement when using the combination in treatment.

Companion Diagnostic Success Stories

The idea of companion diagnostics is not new. There are already companion diagnostics currently improving patient outcomes, see FDA’s List of Approved In Vitro Companion Diagnostic Devices, for more information. However, the number of companion diagnostics in development is also increasing with a growing number of biotechnology and pharmaceutical companies entering into partnerships with diagnostic companies for the purpose of developing companion products.

In 1998, Genentech’s Herceptin was approved for treatment of HER2-positive breast cancer, representing about 20-30 percent of breast cancers. However to effectively identify which breast cancer patients would be a good fit for Herceptin, a diagnostic was developed to test for the presence of HER2. Now there are many HER2 diagnostic tests available.

Recent Companion Diagnostic Approvals Include:

• In August 2011, FDA approved Roche’s Zelboraf and its companion diagnostic for BRAF Mutation Positive Melanoma. The diagnostic called Cobas BRAF Mutation Test identifies melanoma patients who have the BRAF mutation, which is found in about 50% of melanoma patients.
• Also in August 2011, FDA approved Pfizer’s Xalkori for treatment of patients with non-small cell lung cancers that express the abnormal anaplastic lymphoma kinase (ALK) gene. To identify patients with the ALK gene, FDA approved Abbott Molecular’s companion diagnostic, Vysis ALK Break Apart FISH Probe Kit. The ALK gene is found in between 1-7% of non-small cell lung cancer and typically these individuals are non-smokers.
• In July 2012, FDA approved Qiagen’s therascreen KRAS RGQ PCR Kit to determine whether a patient’s tumor contains a KRAS genetic mutation. Detection of the KRAS genetic mutation indicates whether Erbitux will be effective in treating colorectal cancer. In metastatic colorectal cancer where there is no mutation. The FDA also approved ImClone’s, a wholly owned subsidiary of Eli Lilly and Company’s use of Erbitux in combination with FOLFIRI (irinotecan, 5-fluorouracil, leucovorin) for first-line treatment of patients without the KRAS genetic mutation.

Companion diagnostics currently in development or awaiting approval include:

• In October 2011, Life Technologies announced in a press release, an agreement with GlaxoSmithKline (GSK) to develop a qPCR-based molecular diagnostic assay in combination with GSK’s MAGE-A3 cancer immunotherapy candidate. The companion diagnostic developed by Life Technologies will help to identify cancer patients most likely to benefit from GSK’s MAGE-A3 candidate, currently being tested for treatment in resected non-small cell lung cancer and in patients with melanoma that has spread to lymph nodes.
• In March 2012, Abbott Molecular announced in a press release, a collaboration with Merck to develop a FISH-based companion diagnostic designed to test cancer patients for deletion of the TP53 gene. This diagnostic will be used to identify patients that will likely respond best to Merck’s new investigational cancer therapy.
• Just last month, Qiagen announced in a press release, that they had submitted their diagnostic therascreen EGFR RGQ PCR Kit to the FDA as a companion diagnostic with afatinib, an investigational cancer treatment developed by Boehringer Ingelheim. Afatnib is has been submitted for approval in treating patients with locally advanced or metastatic non-small cell lung cancer that have an EGFR mutation identified by the Qiagen diagnostic.

While new companion diagnostics still face challenges common to any medical advancement including reimbursement issues, development timelines and navigating FDA pathways to approval, the future looks bright. Companion diagnostics offer patients the promise of medicines best suited for their specific type of disease. This means that ultimately treatments should be more effective and patients will be less likely to take drugs that provide little or no benefit.