This article has been updated with additional information from Sarah Cannon Research Institute.Originally published July 2.
Extending an existing drug development research pact, AstraZeneca and Sarah Cannon Research Institute this week said they would work together to identify patients for drug development trials based on their genetic profiles.
For this collaboration, AstraZeneca will make its portfolio of oncology small molecule drugs available to SCRI. The drug developer has formed a team to partner with SCRI on the project.
In turn, SCRI will provide its expertise in the development of clinical trials and as a contract research organization, managing trials for multiple early phase oncology compounds. SCRI has partnerships with labs in the UK and in the US that allow it to test patients for various biomarkers on a range of diagnostic technologies. The institute also has access to thousands of patients with various tumor types and a tissue banking protocol in place to enable biomarker discovery and test validation.
AstraZeneca and SCRI have formed a joint steering committee through which representatives from both groups will provide expertise, set goals, and lay out a tactical plan for the molecular profiling project.
"AstraZeneca will have a seat on the steering committee to provide strategic and technical insight into the molecular profiling collaboration to identify opportunities to assess specific therapies against patients’ molecular profiles," Andrew Hughes, AstraZeneca's VP of early clinical development, told PGx Reporter.
AstraZeneca did not name any specific drugs that it would advance with a personalized medicine strategy under this collaboration with SCRI. Hughes noted, however, that the joint steering committee will identify all drugs for which AstraZeneca should identify best responders with the help of genomic profiling.
"We intend to understand the molecular basis of differential response to AstraZeneca drugs for all projects," Hughes added.
AstraZeneca so far has publicly disclosed only a few of its pharmacogenomically targeted efforts. The company markets the drug Iressa in the UK as a treatment for non-small cell lung cancer patients with EGFR mutations. In the US, however, AstraZeneca chose to withdraw its accelerated approval new drug application for Iressa in 2010 (PGx Reporter 2/9/2011).
The company is also developing the ovarian cancer treatment olaparib with a personalized medicine strategy. AstraZeneca is working with molecular diagnostics firm Myriad Genetics to use its BRACAnalysis test to gauge BRCA mutations in ovarian cancer patients in two Phase III trials involving olaparib, a PARP inhibitor (PGx Reporter 6/5/2013).
AstraZeneca is interested in learning more about how patients’ genetic profiles impact their ability to respond to drugs in its pipeline, and it has inked several partnerships with this goal in mind.
The drug firm announced two years ago that it was collaborating with the Netherlands Cancer Institute and the diagnostics firm Agendia to accelerate the development of targeted colorectal cancer drugs. Specifically, under that collaboration, Agendia would provide molecular diagnostics expertise and bioinformatics support and the Netherlands Cancer Institute would make available its biomarker research on various cancers to help AstraZeneca identify colorectal cancer compounds that may be developed with a PGx strategy (PGx Reporter 5/11/2011).
Another collaboration with WellPoint's research subsidiary HealthCore, inked in 2011, could also identify for AstraZeneca additional opportunities for genomically guided drug development. The drug firm is working with HealthCore to conduct comparative-effectiveness studies to gauge how drugs in its pipeline are impacting patient outcomes and healthcare costs. AstraZeneca is using this research to prioritize which drugs to advance in its pipeline and to gain insights into which drugs should be developed in specific genomically defined patient subsets (PGx Reporter 2/16/2011).
As reported by PGx Reporter sister publication Clinical Sequencing News, AstraZeneca and several large drug developers have been outsourcing next-generation sequencing capabilities in their effort to discover drug targets and validate genomic markers. By collaborating with other companies and institutions with genomic technologies, drugmakers like AstraZeneca are able to explore different tests and investigate different response-linked biomarkers before settling on the strategy that works best for a particular drug development project (PGx Reporter 6/5/2013).
In this regard, SCRI is able to provide AstraZeneca access to a variety of genomic profiling tools. For example, the institute offers molecular profiling partners access to a Phase I next-generation sequencing panel that gauges 1,000 hotspot mutations in 35 cancer-related genes.
An SCRI spokesperson highlighted that the technologies currently being used by its partners through its molecular profiling program include next generation sequencing, immunohistochemistry, and fluorescence in situ hybridization, and the institute is considering using whole exome sequencing, gene expression, array CGH, microRNA, DNA methylation, protein arrays.
In the US, SCRI is working with the CLIA-certified and CAP-accredited lab services firm PathGroup. In the UK, the institute has partnered with University College London - Advanced Diagnostics to provide clinical services and develop novel profiling technologies.
Under the partnership with UCL, SCRI has developed a targeted NGS panel that gauges 11 genes for several common cancer types. By year end, the institute hopes to be able to assess more than 30 genes.
SCRI has growing expertise working with pharma to advance pharmacogenomically targeted treatments. According to the SCRI spokesperson, the institute was "heavily involved" in the clinical trials for GlaxoSmithKline's MEK inhibitor Mekinist and BRAF inhibitor Tafinlar, which were recently approved by the FDA with a companion diagnostic to pick out best responders (PGx Reporter 5/29/2013).
Before inking this latest personalized medicine collaboration, AstraZeneca had worked with SCRI since 2005 to conduct early phase studies. "As of 2010, we piloted a program and successfully demonstrated SCRI’s ability to design, as well as deliver early clinical plans," Hughes noted. "The current collaboration is to extend this operating model from a transactional collaboration to a strategic collaboration to scale up the design and delivery capacity."