Two influential nonprofits focused on cancer drug R&D are urging the FDA to take a more flexible approach to clinical work to help triage an influx of new cell and gene cancer therapies making their way to human studies. By changing current IND and manufacturing standards, they say, the agency can cut the time and cost of early-stage work, accelerating the advance of the most promising therapies in the pipeline.
But can they get the industry to agree on data sharing and pre-competitive alliances?
The Parker Institute for Cancer Immunotherapy and the Friends of Cancer Research produced a white paper to persuade the FDA to adopt new exploratory IND guidelines that would allow developers to quickly steer their cell therapy candidates into tiny human studies, allowing researchers to quickly try out therapeutic doses on dying patients who have run out of treatment options.
Evaluating the behavior of cellular products in humans is currently the most effective way to assess safety, since animal models have been unreliable and product quality attributes that predict safety have been difficult to identify.
The groups brought together a variety of cancer drug R&D players together on Friday to discuss the move, including Axel Hoos from GSK and other representatives from Novartis, Celgene, Allogene and more.
To do it right, the advocates say, researchers could divvy up patients into small cohorts who would be given a therapy on a dose escalation basis. A safety monitoring committee could be created to watch out for danger signs and the data could be monitored for safety, efficacy as well as futility.
The groups also want to relax manufacturing standards for very early testing, dropping some of the requirements now in place and reserving them for later stages of development, if the candidate therapy goes on to the next stage of development. “Representative” viral vectors, for example, could be used in gene therapy work, speeding the clinical effort without exposing patients to a significant degree of added risk.
We note that if remarkable efficacy were seen for a product development candidate tested in an “exploratory IND, the requirement for a full IND with more standard manufacturing process development would still apply with the potential for associated delays.
Why not eliminate FDA requirements on cGMP grade plasmids and let the sponsor handle that, bypassing the queues that are forming around a few select providers, they ask. Eliminating the need for an E. coli master cell bank would help cut the time and money needed for one of the first human trials. And adopting “parent-child” INDs, where a main IND could provide the basic content required to approve additional INDs around T cell therapies.
Done properly, they add, the time needed to set up the manufacturing for one of these early-stage therapies could be cut in half.
The biggest challenge, though, could be in advancing their ideas of seeing the FDA coordinate with academia and industry on new “pre-competitive” consortiums that could work together to test various approaches and therapies aimed at the same target — something industry has been loathe to adopt.
Collaborations that promote and facilitate prospective data collection using common data elements and controlled vocabularies to enable cross-study analyses are essential to significantly advance development of cell and gene therapies in oncology. Occurring well before commercialization, such collaborations would provide a proof-of-concept for generating standardized data to inform the early stages of investigational product development. The establishment of a common study platform would foster collaboration across multiple approaches with consistent design, standardized data collection, and analysis.
Taken together these proposals would fundamentally alter the way much early-stage cancer R&D is done. With the phenomenal success of PD-1 therapies like Opdivo and Keytruda and the introduction of the first CAR-Ts, the R&D world has shifted a massive amount of capital into oncology over the past 5 years. That, in turn, has spurred a big increase in the cancer drug pipeline, while also testing the system’s ability to find all the patients and resources needed to prep these drugs for human trials.
Whether the industry can see past the present limitations and adopt a different approach of their own while urging the FDA to evolve its standards will test everyone’s resolve.