Watchdog group files amendment to FDA Citizen Petition
With deaths in clinical drug trials every month since December 2015, Center for Responsible Science (CRS) has updated its July 2015 citizen petition. The petition urges the FDA to update 29 regulations to allow the preclinical test method most predictive of human response is used during drug testing. Current regulations mandate the use of animal models, despite great progress in more human relevant tests.
It is unknown how many deaths and other serious adverse events have occurred in U.S. clinical trials. Serious adverse events are either not required to be reported in public databases (phase I), or are simply not reported as required (phase II and III).
However, given what is known, CRS is strongly encouraging FDA to no longer delay its response to this petition.
On March 15th, six clinical trials on a cancer drug (idelalisib) were halted because of serious adverse events, including several deaths. This followed the FDA’s termination of a phase III trial in February of a blood cancer drug (Pacritinib) after patients died from “intracranial hemorrhage, cardiac failure and cardiac arrest.”
In January, a previously healthy man participating in a clinical trial in France died and five others were hospitalized due to severe adverse reactions, including brain damage. The drug had undergone preclinical tests in four species of animals before first-in-human tests. Even with doses 400 times stronger than those given to the human volunteers, no adverse effects were noted in the animals. The trial was conducted in “full compliance with worldwide regulations,” which further underscores the urgency for new regulations.
In December 2015, a clinical trial participant died from bilateral pulmonary emboli, two months after FDA temporarily halted part of the clinical trial (Zafgen) due to the previous death of a 23 year-old clinical trial volunteer.
In August of 2012, Bristol-Myers Squibb discontinued development of a potential hepatitis C drug after nine participants in a phase II clinical trial of the therapy were hospitalized and one died.
These echo an event in 2006 when six healthy men suffered multiple organ failure during testing of an arthritis and cancer drug candidate called TGN1412, even with a dose 500 times smaller than the dose found safe in preclinical animal studies.
Further tests performed by officials showed that in vitro testing using human cells could have predicted the danger that TGN1412 posed to humans, which the animal tests failed to predict.
“With the recent documented failure of animal-based preclinical test methods to predict safety in humans, it is more urgent than ever that FDA update regulations to broaden drug sponsors’ options to use the most predictive tests available,” said CRS President Dr. Neil Wilcox.
There are human-relevant models that better predict toxicity in humans, but regulations, as currently written, do not include the use of these tests. More predictive test methods will better ensure the safety of volunteers and patients involved in clinical trials and beyond. It is in the best interests of investigators, drug manufacturers, human trial subjects and American consumers that the IND and IDE regulations are modified as requested in this petition, without further delay.
The Center for Responsible Science is a non-partisan, nonprofit advocating for more modern and predictive test methods in drug development.