Guest Director's Update
The NExT Steps in Drug Development at NCI
The FDA’s recent approval of the new agent pralatrexate (Folotyn) for the treatment of peripheral T-cell lymphoma (PTCL) was especially satisfying news for those of us at NCI who have been involved with this drug. Of course, we are always pleased to see a new, effective cancer treatment reach the clinic, especially one for patients with this rare form of lymphoma who have relapsed after or failed to respond to their initial treatment.
NCI has a particular interest in this drug because it is the first agent from NCI’s Rapid Access to Intervention Development (RAID) program to receive FDA approval for a cancer indication. For a program that was in existence for a decade, the fact that this is the first approval demonstrates how difficult it can be to bring a new treatment to patients. Now that RAID has been incorporated into NCI’s Experimental Therapeutics (NExT) program, we believe that efficiencies and improvements in NCI’s drug development efforts are achievable and real.
There is a great deal of excitement about NExT, which is a collaboration between NCI’s Division of Cancer Treatment and Diagnosis and Center for Cancer Research (CCR). The program’s goal is to speed up the drug development process by getting promising drugs—particularly those for pediatric and rare cancers—into human trials more quickly and to prune agents from the development pipeline that are unlikely to be effective, saving valuable resources.
NExT was designed to bring NCI’s diverse drug development efforts into a single pipeline and to follow a formalized, business-like approach to the development of potentially promising therapeutics. At the same time, the broad array of services and resources such as toxicology testing and drug manufacturing that was available to researchers via RAID is still available with NExT.
Where RAID was more focused on aiding researchers with highly specific tasks, drugs accepted into NExT can provide a more comprehensive approach to advancing agents through the development pipeline, including established milestones that drive “go/no-go” decisions about whether to continue NCI’s role in the development of a given agent. The objective is to move drug candidates through preclinical work into first-in-human studies, including phase 0 trials in which nontoxic doses of the agent are tested in a small number of patients. Using advanced imaging and other techniques, in these trials we can determine in a matter of months whether the drug is reaching its intended target and having the intended biologic effects. This will give us more confidence in the decision to move the agent further along in human trials and help to shave at least a year off of the time it typically takes to develop a drug, while also limiting the resources spent developing treatments that will likely never benefit patients.
A number of agents are already in the NExT pipeline, including agents being investigated by researchers from CCR, large academic medical centers, and private industry. (See the box below.) And we’ve already seen an example of how NExT will function. NCI worked with Abbott Laboratories in the early clinical development of its PARP inhibitor, ABT-888, and in testing it in the first-ever phase 0 trial of only 13 patients. The trial demonstrated that the drug, which interferes with a cell’s ability to repair DNA damage, was in fact hitting its biologic target. Now we are working with Abbott to test this agent in phase I and II clinical trials in patients with a variety of tumors.
Although many of the agents in NExT will be supported from preclinical testing through first-in-human studies, the program is open for applicants to enter and exit at any stage in the process. There may be cases, for example, where a research team or private company is already testing an agent in early stage trials in adults, but they may be interested in using NExT to develop the agent for use in a pediatric population, an area in which NCI has unique expertise and resources.
So whether it is serving as a bridge at critical points in the development path, as was the case for pralatrexate, or as a more comprehensive driver of an agent’s development from the earliest stages of preclinical research, we are confident that with NExT we can have many more successes in the coming decade.
Dr. James H. Doroshow
Director, NCI Division of Cancer Treatment and Diagnosis