Establishing a New Standard of Care: Translating Scientific Discovery into Novel Therapies

The delivery of high-quality evidence-based medicine requires integrating the latest scientific discoveries and clinical expertise to address the needs of individual patients.

As the complexity of science and subsequent treatments increase, the way in which we foster their development must also evolve. The process must maintain the thoroughness required to establish safety and efficacy but combine it with a nimble approach that can achieve the urgency required to address human disease and suffering.

Over the last half-century, the translation of scientific discoveries into new medicines has resulted in ground-breaking innovations that have led to steep drops in morbidity and mortality from many devastating diseases, most prominently, cardiovascular disease, cancer, autoimmune disorders, and infections.

These advances are a direct result of the coordinated efforts of government, non-profit foundations, academic institutions, biopharmaceutical companies, and venture capital investors in supporting the advancement of science from bench to bedside.  Each of those participants represents an essential pillar of the drug-development ecosystem, supporting a process that can take more than 10–12 years and cost anywhere from $500 million to more than $2 billion for a single drug to reach patients.

The Drug Discovery Process

The development of new drugs is initiated by fundamental discoveries that identify new molecular targets and biologic pathways that are drivers of human disease. These investigations most often occur in academic laboratories around the globe and are supported by government funding and foundation grants. Investigators, driven by scientific curiosity, the aspiration to improve human health, and the professional requirement to publish, share their insights with the broader scientific community with the aim of stimulating industry a plethora of health care players to apply these insights to human disease.

Traditionally, it is research and development teams in the biotech and pharmaceutical industry that establish the disease relevance of novel targets and develop chemical agents known as ‘drug candidates’ with the goal of re-balancing physiological pathways back to an equilibrium with the potential to improve patient symptoms or cure diseases altogether. These teams refine their drug candidates through an iterative process to select the most favorable characteristics for human use. The optimized therapeutics are tested extensively in both cellular (in vitro) and animal (in vivo) models before final selection to move into clinical trials where they are tested in healthy individuals and patients with manifest disease.  This discovery and preclinical development stage can take, on average, 4–7 years.

Clinical Trials

The next step is to advance promising new drug candidates into human volunteers to identify potential side effects, find the appropriate dose, and establish effectiveness of the therapy. This occurs in staged clinical trials referred to as Phase I, II, and III studies.

In a Phase I study, a small cohort (20–60) of volunteers, often healthy individuals, receive a novel therapy to look for possible side effects and identify the correct dose and administration schedule.

In Phase II studies, hundreds of patients with the disease of interest are treated with the therapy to establish preliminary understanding of the effectiveness, confirm the dose, and further establish safety of the novel regimen.

Finally, in Phase III studies, several hundred to thousands of patients with the disease are treated with the experimental therapeutic and compared to patients receiving the current standard-of-care.  In this final set of pivotal trials, the effectiveness of the therapy is definitively established, and safety is further confirmed.

After 5–8 years of study, only 5–10% of experimental therapeutics advance through all phases of clinical trials and demonstrate a clear benefit for patients.  After achieving this milestone, the clinical trial data are submitted to regulatory health agencies around the world, such as the FDA, for final review and approval.  Only then do these new therapies become broadly available to patients.

The Role of UPMC Enterprises Translational Sciences

At UPMC Enterprises, we take an active role in expediting the development of promising scientific projects and by providing scientific and business planning support as well as financial investment across all stages of development.  We leverage the extensive clinical and scientific expertise across the UPMC system and the University of Pittsburgh to ensure that we select projects that are addressing the most pressing clinical needs with the most advanced science.

Once a project enters our pipeline, our novel model efficiently supports and progresses early-stage discoveries from academic laboratories into the clinic.  Under this structure, we partner scientific investigators with virtual pharmaceutical development and commercialization teams and support the mandatory preclinical studies with the rigor required of the biotech industry. This allows us to accelerate preclinical validation and clinical translation by bringing together the academic scientists with the drug developers.

This unique model is how we plan to reduce drug development timelines and costs, rapidly bring promising scientific discoveries to patients and generating both the societal and financial returns required to change the practice of medicine.