Cancer Researcher Dan Von Hoff, M.D. Advocates for “Context of Vulnerability,” A Powerful New Paradigm for Targeted Drug Development
Renowned cancer researcher Dr. Daniel Von Hoff and his team at TGen are fervent believers in a new approach to developing novel therapies for patients with pancreatic cancer. They are guided by a rationale dubbed the "context of vulnerability." Dr. Von Hoff provides case studies and explains how this powerful paradigm has already led to promising discoveries and is changing the future of oncology drug development.
Phoenix AZ —February 17, 2009 — Today, Medelis, Inc., a global oncology contract research organization, has published a free new downloadable abstract, "Context of Vulnerability: A Powerful New Paradigm for Targeted Drug Development." In this extensive interview, renowned oncology investigator Daniel D. Von Hoff, M.D., a founder of Medelis and a member the National Cancer Advisory Board, advocates for this powerful new drug development paradigm that is generating impressive results in the war on pancreatic cancer, the most deadly of all cancers.
“People say we have lost the war on cancer and it is so discouraging to the people who deliver the care every day, the people who are seeing those curves turn around,” laments Dr. Von Hoff. “The fact is that the rising tide of cancer deaths hasn’t just been stemmed – it’s been turned around. Mortality, in terms of absolute number of deaths, has been down for two years in a row. It should have been going up like a rocket because we’re all aging.”
Dr. Von Hoff’s team believes a new approach for targeted drug development is the key to developing powerful targeted therapeutics. He advocates heavily for a rationale dubbed “context of vulnerability,” a term coined by TGen's Spryo Mousses, Ph.D. It refers to the genetic configuration in a patient’s tumor that makes it susceptible to a specific drug. “Context of vulnerability provides the genetic rationale for a targeted therapy,” Dr. Von Hoff explains.
CHANGING DRUG DEVELOPMENT
Dr. Von Hoff proposes that oncologists use context of vulnerability as the “sixth vital sign” because “it holds a key to optimizing therapy for an individual patient.” This step can play a critical role in guiding drug development, improving patient care, and developing powerful new agents.
Dr. Von Hoff: “If you let context of vulnerability guide drug development, you would put only those patients who have the appropriate susceptibility to the drug on trial. This optimizes your chance of seeing efficacy with a much smaller n. It’s essentially how Herceptin® got approved with an n of 480. If they hadn’t pre-selected patients for the context of vulnerability, estimates say that it would have taken about 23,000 patients to get the drug approved.”
ESTABLISHING CONTEXT OF VULNERABILITY
“One way to establish the context of vulnerability is to work backwards from the result,” Dr. Von Hoff explains. “For instance, in a phase I or phase II trial, you treat a certain number of patients, and when someone responds, you have to ask yourself, ‘Why did that patient respond? What was the vulnerability in this specific tumor or patient?’ The patient either had a genetic lesion or tumor stroma that was susceptible to the drug in some way.”
In the abstract, Dr. Von Hoff provides a detailed look at the promise and potential of “context of vulnerability” and the opportunity it creates in the war on cancer:
- How context of vulnerability provides a genetic rationale for a targeted therapy
- How to establish a patient’s context of vulnerability
- How using context of vulnerability to guide drug development can improve your chance of seeing efficacy with a much smaller n
- Incorporating context of vulnerability as the oncologist’s “sixth vital sign”
- A case study of context of vulnerability in use and how it improves patient care and new agent development
- The gap between known contexts of vulnerability and available therapeutics
- How CMOs can flip their drug development planning to leverage this approach
- Feedback from the FDA, national and international groups
- The promise and potential of this approach
- Targeted therapeutics and the future of oncology
A member of President Bush's National Cancer Advisory Board, Dr. Von Hoff's major interest is in the development of new anticancer agents both in the clinic and in the laboratory. His laboratory interests and contributions have been in the area of in vitro drug sensitivity testing to individualize treatment for the patient. At present, he and his colleagues are concentrating on the development of molecularly targeted therapies with a focus on pancreatic cancer.
Dr. Von Hoff currently serves as Senior Investigator and Head of Translational Research at the Translational Genomics Research Institute's (TGen) Translational Drug Development Division and Head, Pancreatic Cancer Research Program in Phoenix, Arizona. He also serves as Chief Scientific Officer for U.S. Oncology and the Scottsdale Clinical Research Institute and is a founding shareholder and chair of the medical advisory board of Medelis.
The abstract is the fifth in Medelis' complimentary "Peer Perspectives in Oncology" Q&A series, which brings together respected researchers to discuss issues that face Chief Medical Officers today: rising costs, optimum patient accrual, targeted therapeutics, patient safety, FDA regulations, efficacy, budgets, and timelines. Previous issues include “The Lost Opportunity in Phase I Oncology Trials,” “Preclinical Trials: A Nuanced Approach to Get Into the Clinic Faster,” “The Complete Phase IB,” and “Patient Safety in Clinical Trials.”
The abstracts are available for download in our Insider Abstracts section.
About Medelis, Inc.
Medelis, Inc. is an oncology contract research organization providing a total solution for biotechnology and pharmaceutical companies seeking rapid drug development and approval. Medelis' medical founders, team physicians and clinical trial management physicians, including Dan Von Hoff, James Gourzis and Michael Gordon, are internationally-recognized oncology thought and opinion leaders who understand the future of personalized medicine and threshold of credibility trials. Offerings include strategic plans for regulatory approval from phase I through final approval and complete oncology clinical trial design, management and execution.
Medelis is privately-held and located in Phoenix, Arizona with other U.S. locations in Nashville, Boston and Reno. Medelis Europe, which also delivers complete oncology drug development services from preclinical through marketing approval, is headquartered in Port Vendres, France.
