By Hua Gong
Companion diagnostics (CDx), which identify and detect biomarkers to predict whether a drug works or causes adverse effect in patients, has emerged as an exciting new field. With the cost and hurdles for new drug approval getting increasingly higher, pharmaceutical companies have begun to explore companion tests in order to develop safer, more effective drugs. The value of CDx tests has already been demonstrated by a number of marketed products, such as HercepTest for Herceptin and K-RAS mutation tests for Erbitux and Vectibix.
Oncology is the most developed segment of this market with products and tests representing more than 48% of the CDx development market. Recently, the FDA approved two drugs and their accompanying tests. Pfizer’s Xalkori for lung cancer, which was approved in record time, has had great results for roughly the 5% of nonsmall-cell lung cancer patients that carry the ALK/EML4 fusion gene as determined by a test from Abbott Laboratories. The other drug, Zelboraf from Roche and Plexxikon, also has produced remarkable improvements but only for roughly half of melanoma patients whose tumors have a bRAFV600 mutation. The FDA approved a test from Roche’s diagnostics division to detect the mutation.
The CDx Development Process
CDx development can be divided into four steps:
- Biomarker discovery includes identifying disease-relevant biomarkers and developing a test to measure each biomarker.
- Analytical validation ensures that the performance of the test meets regulatory requirements.
- Clinical utility and validity test, the most important and costliest part of development, has to prove that information generated has value in guiding clinical practice for patient management as required by the payers.
- Data analysis and regulatory submission determines CDx performance by correlating the test’s analytical data with clinical outcome information and then submitting the data package for regulatory approval.
Coordination Of Clinical Trials In CDx Development
Despite these proven successes and ever-increasing awareness of companion diagnostics, pharmaceutical companies are still moving slowly to adopt the new paradigm of codeveloping companion tests along with new drugs. The regulatory hurdles, physician and patient acceptance, insurance coverage, IP strategies, and other barriers remain unsettled for this young field. A well-coordinated plan of clinical trials can overcome some of these issues.
It is important to leverage both drug development and diagnostics expertise in trial design and execution. In order to prevent a slowdown of drug development due to the diagnostics timeline, you can use retrospective samples or samples from pilot trials to validate the biomarker before launching clinical trials. A preanalytical characterization of samples can help to define optimal tissue requirements. Also, address regulatory hurdles early on by scheduling pre-IDE (investigational device exemption) meetings and negotiating labeling of drug and diagnostics before approval. Regional differences in CDx product review and approval need to be considered.
Improvement Of Drug Development
Many business models have been adopted for CDx development: Dx/Rx in one entity (Roche and Genentech), Rx/Dx partnership (Pfizer/Abbott), Rx acquire Dx (Novartis/Genoptix model). Regardless of which model one takes, early planning between the pharma and diagnostics companies will likely increase the chance of success in the development. Coordination of development timelines is essential in CDx development.
The recent success of Xalkori and Zelboraf serves as a testimony why companion diagnostics should be part of a drug development strategy. Pharma companies are more interested in stratifying patients for their clinical trials so that their drug will more likely demonstrate efficacy in the selected patients, leading to regulatory approval. Budget-conscious policy-makers and payers like the idea of paying to treat only the patients who will benefit from the treatment, and physicians and patients are also keen as treatments are more likely to work for the patients. Innovation in technologies is expected to play a pivotal role. This also presents a great business opportunity; the global CDx market generated sales of $1.30B in 2010 and is predicted to be worth $3.45B by 2015.
Hua Gong, M.D., Ph.D., is the executive director of medical diagnostics at Premier Research. Dr. Gong has more than 12 years of experience including both R&D and clinical expertise in the development of diagnostics.