We don’t need new regulation to form n=1 trials and offer them to patients. It is time to stop looking for changes in regulation to give us permission to pursue these activities. In short it is time to deliver on the promise of precision medicine.
This morning I received word from a medical oncologist in Southern California that his 13 year old nephew had died following his fight with glioblastoma multiforme (GBM). I oftentimes receive requests from physicians and patients who are trying to successfully navigate the clinical trials landscape. In this particular case, I was asked to try and find open and accruing clinical trials for this adolescent. We were armed with an informative genomic report and had hope of finding a targeted treatment to help. When publicly listed studies were found to be closed to accrual, we worked to identify an Expanded Access opportunity for this patient. Unfortunately, although FDA approves almost all applications, the number of Expanded Access opportunities are embarrassingly low (less than 1,200 individual cases are approved by FDA annually[1]) and, in this case and in many others we were unable to secure access to a targeted treatment in time.
My next e-mail alerted me to an editorial in The Hill written by two neurosurgeons at Weill Cornell Medicine. These physicians essentially retold the story of this young GBM patient. They called for n=1 studies where customized treatment is provided based upon genetic analysis. In my case the patient had whole genome sequencing performed and actionable mutations. They call for access before patients are imminently terminal. In my case we were able to apply omic recommendations to open and accruing clinical trials, excluded studies unlikely to offer potential benefit, and focused in on the studies we did find that had an informed chance of working. None of the listed studies were available. I am convinced that had these studies still been accruing patients, or the promising investigational product been for compassionate use and we convinced a biopharmaceutical company to release a targeted investigational product, the outcome in this case would have been positively impacted.
Dr. Souweidane and Dr. Greenfield’s editorial is a call to action for the FDA, biopharmaceutical companies, foundations, researchers, oncologists and patients. It is the same call to action issued by former Vice President Joe Biden at ASCO in 2016. It is the same call to action issued by Janet Woodcock, M.D. in 2017 and it is the same call to action I issue today.
We don’t need new regulation to form n=1 trials and offer them to patients. Clinical trials are largely consistent and as such we can standardize the way data is collected across pathways. Right now we can agree upon core safety and efficacy endpoints for protocols, match patients to targeted therapies, deliver investigational products efficiently, make it easier for oncologists to participate and collect quality data to inform the development of investigational product and the care of patients facing difficult diseases today and those who will face these situations in the future. Studies like I-SPY, MATCH, SIGNATURE and TAPUR are already testing promising investigational products in smaller populations of patients.
It is time to stop looking for changes in regulation to give us permission to pursue these activities. In short, it is time to deliver on the promise of precision medicine.
My day ended with an e-mail stating that Right-to-Try was passed and is heading for the President’s desk. In short, biopharmaceutical companies and treatment sites will no longer need to fear product development or legal risks when deciding to provide promising investigational treatments to patients. As a community let’s meet these companies half way, by providing a viable operational solution to make precision medicine a reality by offering better access to investigational product as well as approved treatments to those that need it.
[1] The average number of single patient emergency and non-emergency Expanded Access cases approved between 2010 -2015 was 1,185.
