a diagnostic with a therapeutic. The agency has indicated that it wants to be flexible in what is required of sponsors, and will sometimes accept preclinical data instead of extensive clinical testing of drug combinations. FDA welcomes pre-IND consultations, especially for innovative study designs. “We still will have to show the contribution of the agents, but the encouraging part is that how we do that is something that can be discussed,” as Dr. Hohneker pointed out. More effort should be made to make FDA regulations compatible with EMA regulations so as to foster global drug development, some participants suggested.
To help tackle some of the other complex legal issues linked to developing combination therapies, such as IP and indemnification, there could be more reliance on NERFs and the development of standard clauses and core principles to make legal negotiations more expedient. Identifying key decision makers, who are knowledgeable about the legal issues, can also be helpful in legal negotiations. Antitrust issues are not likely to pose barriers to collaborations among companies, particularly if they will not limit competition; if the collaborators do not already have entrenched products; if the collaboration is limited to core research efforts; and if it is possible to show benefits that the collaboration will achieve that could not be achieved as easily on an independent basis. It is possible to obtain prior guidance with the FTC or the DOJ about antitrust issues. Antitrust lawyers can also advise research and development efforts.
There are several examples of collaborations in the early development as well as the clinical testing of combination cancer therapies. These collaborations show that barriers are not insurmountable and provide examples for others to follow. Particularly notable innovative clinical testing examples are the I-SPY 2 TRIAL and the BATTLE 2 trial. Several scientific tools to aid cancer combination therapy development are available in the public domain, including GSK’s epigenetic toolbox and preclinical data, NCI’s mechanism-of-action assays and preclinical models for combinations, as well as the investigational agents that NCI makes available for preclinical testing.
Several participants stressed the importance of doing whatever it takes to facilitate collaboration in the development of combination investigational cancer therapies. “There is really an urgency to identify solutions for the barriers because we have patients at stake,” said Dr. Hohneker. Dr. Mendelsohn agreed with the urgency to speed up combination drug development, given that “one-third of our patients will not live 5 years— that’s a half-million people a year.” Dr. Hohneker concluded the conference by stating, “The takeaway is that for success and learning, it takes a team of people who are very committed and passionate, and willing to work together to come up with the solutions, as well as strong collaborations, persistence, good science, and the willingness to learn.”