Opportunity Still Exists for Companion Diagnostic Partnerships

Companion diagnostics (CDx) hold the promise to make drug therapies safer and more effective. At the same time, breaking the conventional trial-and-error cycle for prescription medications makes health care more cost-efficient by allowing health care providers to give the right drug to the right patient. Pharmaceutical companies increasingly understand that incorporating a CDx strategy into drug development programs at early stages may expedite trials and, ultimately, the drug approval process. Utilization of CDx at a time when the health care market is increasingly focused on achieving improved outcomes and cost efficiencies in turn further drives continued interest in CDx test development. To date, CDx development has been achieved largely through partnerships between pharmaceutical and diagnostics companies. Big name diagnostic companies such as Abbott Molecular, Qiagen, and Foundation Medicine are deeply invested in these partnerships. Currently, 155 pharmacogenomic biomarkers are included in Food and Drug Administration-approved drug labels. The pharmaceutical industry is invested in a more customized drug development model. The Personalized Medicine Coalition estimates that 30 percent of all treatments in late clinical development rely on biomarker data, as do 50 percent of all treatments in early clinical development and 60 percent of all treatments in preclinical development. '“If we could look back to the first CDx case, HER2/Herceptin, and if we could get the true story, I’m sure there were bumps and bruises along the way,” Harry Glorikian, a health care consultant, tells DTET. “Although there are still problems, as science doesn’t always progress as expected, these partnerships now go a lot smoother. We know how to handle problem ‘A’ or avoid it altogether. Mistakes of the past won’t be made again.” The financial arrangements and interworkings of these collaborations are often not disclosed, and while there is no objective measure of the success of these ventures, experts predict these joint ventures will continue and result in a heightened number of commercial launches of codeveloped drugs and CDx tests over the next 10 years. “If the United States is driving towards outcomes-based system and institutions are reimbursed based on outcomes, they are going to demand products that help them achieve those better outcomes,” Glorikian explains. “If there are three drugs that basically do the same thing, you can select on best price, but nobody wants to play the price game. So, if I give you a tool to achieve a better outcome by targeting the ideal population better or improving adherence, you may decide to use my drug.” Sampling of Recent CDx Partnerships The sampling of CDx partnerships announced this summer demonstrates the breadth of partnerships—varying in stage of compound development and the range of medical conditions involved (oncology, infectious disease, reproductive health):

• Ventana Medical Systems (a Roche company; Tucson, Ariz.) announced in July a new partnership with Merck for the development and commercialization of a CDx for an undisclosed oncology target. Ventana reports working with more than 45 biopharmaceutical partners on more than 180 collaborative projects to develop and commercialize CDx globally.
• AstraZeneca said the circulating DNA (ctDNA) test it is codeveloping with Roche (Switzerland) will be designed to identify epidermal growth factor receptor (EGFR) mutations in both tumor tissue and plasma from patients with non-small-cell lung cancer (NSCLC). The test will optimize the clinical development of investigational compound AZD9291 for patients who are resistant to first-generation EGFR tyrosine kinase inhibitors (TKIs).
• With longtime partner Qiagen (Germany), AstraZeneca will codevelop a test to identify patients that can be treated with Iressa, an EGFR-TKI. Iressa, already approved in 65 countries, is indicated for the treatment of adults with locally advanced or metastatic NSCLC with activating mutations of EGFR-TK. The test uses a highly sensitive assay to detect EGFR mutations in small fragments of plasma ctDNA. AstraZeneca and Qiagen said the test has demonstrated “robust and reliable” identification of EGFR mutation status using samples from the Phase IV IRESSA Follow Up Measure study.
• Biocartis (Belgium) and Abbott (Abbott Park, Ill.) will leverage Biocartis’s molecular diagnostics system, Idylla, and Abbott’s regulatory, scientific, and commercialization expertise to develop multiplex biomarker panels for use in partnership with pharmaceutical companies’ clinical trials.
• Ferring Pharmaceuticals and Roche announced a collaboration to combine diagnostic testing technology from Roche with Ferring’s human cell line-derived recombinant follicle-stimulating hormone, currently in phase III development. This combination will personalize infertility treatment dosing based on a woman’s anti-Müllerian hormone levels.
• Cepheid (Sunnyvale, Calif.) announced earlier this summer a new collaboration with AstraZeneca, Cubist Pharmaceuticals Inc., and GSK to promote “transformational change” in infectious disease therapy with the development of a rapid diagnostic test that can target multi-drug-resistant pathogens and aid the appropriate use of antibiotics. The group will work to extend the number of body sample types utilized by the Xpert Carba-R rapid test. Xpert Carba-R is commercially available outside the United States and is targeted for a commercial U.S. release in 2015, subject to approval.
• Foundation Medicine (Cambridge, Mass.), in June joined pharmaceutical companies Amgen, Genentech, Pfizer, and AstraZeneca in the Lung Cancer Master Protocol (Lung-MAP) trial. Lung-MAP is a multidrug, multiarm, biomarker-driven clinical trial for patients with advanced squamous cell lung cancer. Foundation Medicine’s comprehensive genomic profiling will be used to match patients to one of five experimental drugs—four targeted therapies and an anti-PD-L1 immunotherapy—based on the tumor’s genomic profile.

Takeaway: Codevelopment of CDx through diagnostic-pharmaceutical partnerships will continue to permeate the industries. These collaborations will culminate in accelerated commercial availability of targeted therapeutic products that will assist the health care system to achieve improved outcomes at a reduced overall cost. Side Box: Smaller Companies Can Participate Too While headlines trumpet the major partnership players—Abbott, Roche, Qiagen, and Foundation Medicine—some startups have been able to establish collaborations with pharmaceutical companies. Smaller companies’ lack of a footprint may make them less ideal partners. “If I’m a pharmaceutical company and I am going to launch a drug globally, I need a partner that can go global with the product,” explains Glorikian. “There may be kinks if the [smaller company] doesn’t have marketing, distribution, and commercialization in place.” Startups like Nodality (San Francisco) have positioned themselves in active pharmaceutical partnerships, although to date no commercial products have been produced. Nodality’s proprietary platform, Single Cell Network Profiling, which enables functional characterization of disease-associated signaling, is being applied to develop molecular diagnostics in cancer and autoimmune diseases. Nodality is also collaborating with pharmaceutical partners on patient stratification and companion diagnostics development and biomarker discovery and development. Existing partnerships include CB Pharma, Pfizer, and Janssen Biotech.