Abstract BodyComparative Oncology-: An introduction and the state of the field
Cancer Drug Development is Difficult and Fraught with High Failure Rates
Fewer than 3% of cancer drugs entering human trials advance to human approval. It is critical that the conventional approach to oncology drug development be improved, so that new medications are available for use faster. Many development failures occur late in drug development (so-called late attrition), moving disproportionate costs to patients and drug developers as compared to a “fail-early model” of clinical development. Moreover, promising innovations are often stuck between early research and discovery and clinical trials due to lack of convincing data in support of their potential efficacy, or a perception that preclinical cancer models are not predictive to justify the risks of human trials. Unfortunately, this is to the great loss of cancer patients.
Comparative Oncology: A Game-Changing Approach to Better, Cost Effective Oncology Drugs
When developing new cancer drugs, Comparative Oncology involves the inclusion of dogs with naturally occurring cancer in clinical trials, as compared to novel or repurposed drugs that are tested to answer questions that cannot be answered in conventional animal models of cancer or human clinical trials. Comparative Oncology seeks to address the current challenges in oncology drug development through the study of naturally occurring cancers, primarily in dogs, that share the same biological complexity seen in human cancers. Given the unquestioned need for the translational and clinical infrastructure that currently exists to deliver the promise of Comparative Oncology medicine, there is an urgency to expand the use of a Comparative Oncology process with a parallel/integrated cancer drug development path.
Even though thought-leaders and experts in the field believe that dogs with cancer provide a unique opportunity to improve the development path of new cancer drugs, this modeling approach is underutilized. This is despite significant investments in the field, such as the launch of the NCI-Comparative Oncology Program, as well as similar efforts and research supported by the extramural NIH, academic research centers, and comprehensive cancer centers across the US with the endorsement of the Institute of Medicine through its hosting of a strategic meeting focused on this opportunity, as well as by the launch of several internal programs in Comparative Oncology within the pharmaceutical and biotech industries.
Comparative Oncology is an untapped resource.
Quantification of the value of the comparative approach to cancer drug development includes financial proforma models as well as assessment of the value of not guessing in answering previously unanswered questions. Nonetheless, defining this value is not simple because of the inherent complexity of cancer drug development and the many data inputs that advance a given drug development path.
Given the interest and investment in Comparative Oncology, it is attractive to believe that more widespread adoption of this approach will simply come from more examples and/or greater awareness (i.e., “more chances at bat”). An alternate view of the field may recognize a potential pitfall that results from the perspective that Comparative Oncology is merely a preclinical strategy that is considered before human phase I entry, rather than as a parallel integrated strategy for clinical development teams using data from studies with canines to answer questions and optimize Phase II and Phase III human trials. Furthermore, solely positioning Comparative Oncology as a preclinical opportunity results in increased competition at the tail end of conventional preclinical discovery/development in what may be described as a shrinking market, where most development resources may have already been utilized. Viewing Comparative Oncology as a parallel and integrated approach with human trials results in a distinct and potentially broader strategic approach with better use of financial resources. This approach may promote collaborative relationships between human and animal health drug development/ commercial teams with preclinical R&D. This alternate focus on parallel/integrated drug development, that seeks to optimize Phase II/II trials, will result in better definitions of dose, schedule indication/biomarkers of response, and drug-target mechanisms of action. This will collectively increase the chances of success in human Phase II and beyond.
Additionally, this approach will de-risk human R&D in many ways, and may create new streams of revenue to support these critical parallel and integrated translational studies. Disrupting cancer drug development redefines roles and reduces costs of conventional animal health R&D and provides early exits for human cancer drug development. Such early exits will result from animal health interests in early data from human health assets.