Many people take for granted that the medication they have been prescribed by their physician will adequately treat or cure their ailment. Yet the reality is that a large number of the drugs prescribed come with a surprisingly low success rate.

According to analysis1 by Nicholas J. Schork, PhD and director of Bioinformatics and Biostatistics at the Scripps Translational Science Institute, some of the highest-grossing drugs in the U.S. help as few as 1 in 25 patients. Standard practice includes treatments given based on a physician’s experience with similar patients, meaning medications are prescribed for a “typical patient” with the disease or medical condition.

But not all disease is homogeneous. The more we learn about disease biology, like tumor characteristics in oncology and the genetic components of rare diseases, the better we understand why single-target treatments can fail.

Hope for a solution has arisen with the development and evolution of the principles of precision medicine, where innovations are making therapeutic breakthroughs possible on a patient-specific basis.

Through precision medicine, a range of new technological advancements are helping to improve our understanding of diseases and changing the way physicians diagnose and treat. The result is more precise and powerful healthcare that is customized to the individual.

“In the last couple of decades, we’ve gone from a one-size-fits-all approach to a targeted one based upon the biology of disease and identification of the specific therapeutic target within that disease state,” says Dr. Steve Anderson, chief scientific officer at leading contract research and development services company, Covance.

“In areas like oncology or rare diseases, highly personalized therapeutic approaches are rapidly becoming a reality.”

Navigating the development cycle

The quest for personalized care for each patient means providing the right drug to the right patient at the right time. Achieving a tailored therapy is not a simple process, but breakthroughs in developing precision medicines are making dramatic in-roads.

“In areas like oncology or rare diseases, highly personalized therapeutic approaches are rapidly becoming a reality.”

In the last few years alone, precision medicines based on cell and gene therapies have emerged and are predicted to grow significantly. One indicator is from regulatory agencies such as the Food and Drug Administration (FDA), that announced an increase in the number of clinical reviewers to assess and help approve an expected ten to 20 such therapies per year by 2025. Global financing for precision medicine also rose by 64% to more than $17B USD in 2018.

Investment and research is clearly beneficial to providing improved medicines on a personalized basis, with highly specialized capabilities needed at every stage of the process.

According to Anderson: “As we look at the development of these novel therapies, it is becoming a very highly competitive field and there are numerous expedited regulatory approval pathways, so moving quickly though the drug development cycle to ensure success is essential.

“This means the ability to transition quickly from non-clinical into clinical development and remove as much whitespace as possible is critical. During development, looking ahead to the post-approval phase and understanding how to differentiate is also very important. Having that forward-thinking mind-set and perspective from a full-service provider is a huge benefit to sponsors.”

“Clients choose Covance because we are a full-service CRO, with specialization in precision medicine,” continues Anderson. “We can work with sponsors through all phases of development to transition quickly between these phases, such as from preclinical to clinical, to save client’s time.

“In developing the appropriate nonclinical models, we can help sponsors understand the therapeutic candidate’s mechanism of action and establish the potential for efficacy and toxicity in humans prior to clinical studies.

“For lab testing, we can work with sponsors in screening patients for the appropriate biomarkers to stratify patient populations and establish inclusion criteria in clinical studies. Moreover, in support of innovative clinical development programs, we have the ability to help with trial design and adapt the design as the study progresses.

“When there is a biomarker that proves critical to establishing whether the therapy will be effective in patients, Covance can support the co-development potentially leading to a companion diagnostic in collaboration with our parent company, LabCorp, making that diagnostic commercially available at launch.”

Putting the patient first

Trial design in precision medicine creates a fresh set of challenges for sponsors already adapting to the evolving and sometimes region-specific regulations and tightening of budgets.

“Sponsors must manage the relationship between all stakeholders in the delivery of precision medicines.”

Precision medicine trials must focus on smaller, targeted populations, while remaining flexible in design. A sponsor may start with one hypothesis, often driven by a biomarker strategy to identify patient cohorts, and need to adapt that design as they move through the development cycle.

Another significant challenge for some precision medicines is the high upfront cost, especially for cell and gene therapies that are potentially single-dose, curative treatments. However, Anderson predicts that prices are likely to fall as the industry develops manufacturing efficiencies, streamlines development and approval pathways, and competition increases.

“Sponsors must manage the relationship between all stakeholders in the delivery of precision medicines. They must work with payers determining coverage for the therapeutics or diagnostics, diagnostic developers, regulatory agencies, and so on.

“This collaborative spirit of all impacted stakeholders finding the right path forward helps to balance the individual benefit with the broader cost to the healthcare system. Most importantly, a patient whose disease characteristics and unique genetic makeup are taken into account has a better likelihood for response to today’s innovative medicines.”

1. Schork, N. (2015). “Personalized medicine: Time for one-person trials.” Nature, Vol 520: 609-612