US FDA Commissioner Scott Gottlieb touted the use of combined-phase studies, or "seamless trials," by oncology sponsors, indicating that the method could become more widely adopted beyond the field of cancer drug development.
Speaking at the Regulatory Affairs Professionals Society Regulatory Convergence Conference Sept. 11 in Oxon Hill, Md., Gottlieb pointed to seamless trials as part of a broader plan for the agency to reduce drug development costs in the clinical phase.
Seamless trials involve one adaptive study where the phases are separated by interim looks. Gottlieb says such an approach saves time, reduces costs and the number of patients that have to be enrolled in a trial.
FDA has identified 40 active investigational new drug applications (INDs) for large first-in-human oncology trials that use the seamless trials, according to Gottlieb. Sponsors of these trials will usually add cohorts to investigate doses and activity in a variety of cancers.
"Seamless designs are particularly advantageous for drugs that work in a variety of diseases, allowing rapid evaluation of the drug and potential approval under our accelerated approval pathway," Gottlieb said.
"We’ve seen examples where this approach has allowed the rapid development of drugs in multiple different tumor types," Gottlieb said. "If we had to stop and start formal Phase II trials in each different organ system where a cancer arose, it could have been a protracted process. This approach is well suited to the kinds of drugs that are being developed now, where drugs intervene on common elements found across multiple kinds of disease states."
Gottlieb added that Oncology Center of Excellence (OCE) Director Rick Pazdur is looking at ways to better evaluate and incorporate the seamless trials into the agency's wider effort to "modernize" the approaches for drug development.
The use of seamless trials, however, may not stop with oncology drug development. Gottlieb noted that the approach has been used with a few newer immunological therapies, and that it may also be used in developing drugs that target specific molecular defects.
"Seamless designs are particularly advantageous for drugs that work in a variety of diseases, allowing rapid evaluation of the drug and potential approval under our accelerated approval pathway," Gottlieb said. "These new approaches are also highly consistent with the goals of the 21st Century Cures Act and the recently passed FDA Reauthorization Act."
Gottlieb went on to announce that the agency will "begin work" on at least ten new disease-specific development guidance documents over the next year. These will include areas of unmet medical need, such as Amyotrophic Lateral Sclerosis (ALS), he said.
The commissioner's remarks – which factor into the broader conversation of reducing drug prices by cutting down on development costs – come on the heels of the release of a Journal of the American Medical Association (JAMA) study, which found that the cost to successfully research and develop a cancer drugs is $648m, rather than $2.6bn usually cited by biopharma. (See sidebar for related story.)
Gottlieb acknowledged that although there is some criticism of cost estimates in developing a drug, he noted that the cost of capital is affected most by risk failure on top of the direct costs of research and development.
"As the risk of failure grows, entrepreneurs seek a higher potential return in order to support the initial investment," Gottlieb said. "The cost of capital is also significantly impacted by the time anticipated it will take to develop a new medicine."
Gottlieb's comments also come just days after he outlined the agency's plan on the pre-clinical front to make drug development more efficient. Speaking at Research America's National Health Research Forum Sept. 7, Gottlieb indicated certain second entry therapies could require less pre-clinical data. (See sidebar.)
The commissioner will provide details on modernizing the role of FDA's medical staff Sept. 29 at the National Press Club.
Modernizing Data Evaluation And Review
Gottlieb also outlined efforts the agency is taking to make evaluation of clinical data by sponsors, as well as review of data by FDA, more efficient.
He touted the use of more advanced computing tools and more sophisticated statistical methodologies, such as modeling and simulations, as a starting point. The commissioner, however, noted that access to such tools is limited, and that he is "directing an effort to try and increase our investment in these computing tools."
Gottlieb cited several benefits of advanced tools and methodologies, including their ability to evaluate safety and efficacy of different doses, help select the best dose for populations and subgroups and evaluate the reliability of surrogate endpoints.
"These tools are especially important to our use of modeling and simulation as a part of drug review, not only in our Division of Pharmacometrics, in the Office of Clinical Pharmacology, but across our review program," Gottlieb said. "Almost 100 percent of all new drug applications for new molecular entities have components of modeling and simulation embedded."