Report reveals under-reported problems, patient safety concerns
Sanofi’s clinical trial continues months after reported brain damage. Toll: 1 dead, 7 injured.
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Tuesday, January 28, 2014… Sudden collapse of the big multinational Sanofi study of its myelofibrosis drug fedratinib exposed serious problems in clinical trial patient safety monitoring. That’s the conclusion of a Special Patient Safety Report appearing today in MPNforum.
The abrupt termination of the Sanofi Phase III clinical trial in November stunned patients and site investigators. Reportedly, one death and seven cases of Wernicke’s encephalopathy (WE), a potentially deadly neurological disorder, occurred in the course of the clinical trial.
A Mayo Clinic (Rochester) neurologist confirmed one WE case this spring, a 71 year old woman with myelofibrosis on clinical trial. That case study was published in the medical literature in August but the Sanofi drug trial continued until mid-November. News of the severe adverse event did not reach supervisors, the FDA, or field investigators. Despite this confirmation of Wernicke’s encephalopathy, no change was made in the clinical trial protocol. Physicians at the clinical trial sites remained ignorant of this unanticipated serious and potentially fatal development. Patients were not informed of the expanded trial risk.
The FDA confirmed to MPNforum: “Sponsors investigating a drug under an IND (Investigative New Drug) are required to notify the FDA and all participating investigators, in a written IND safety report, of any adverse experience associated with the use of the drug that is both serious and unexpected.”
According to the MPNforum report: “Revealing the deep and deadly ignorance that permeated the trial, just a few weeks before Sanofi pulled the plug, the company made a milestone payment confirming fedratinib achieved acceptable safety and efficacy results. Sanofi was only days away from filing its FDA approval application when it reversed course and unceremoniously backed out. Trial closed. Drug development terminated. Every myelofibrosis patient on the trial out in the cold. Doctors, patients and overseers all taken by surprise as the seemingly successful study of a good drug spectacularly blew up right at the finish line….”
On November 18, 2013 Sanofi terminated its trial and advised patients to seek medical testing and advice from their physicians. The giant French drug company released scant details and refused to answer questions. The FDA claimed it was unable to respond to Freedom of Information Act requests for additional information due to mandated restrictions.
According to the MPNforum report: “More than two full months past trial termination, no official public accounting has been provided, no data on death or injury was made available to patients or their physicians. At least some of the patients are believed to have suffered irreversible neurological and cognitive damage. No one has taken responsibility for failure to diagnose, failure to report, or failure to terminate the trial earlier.” The full story can be accessed at: www.mpnforum.com/jakarta
- Wernicke’s encephalopathy (WE) is a serious neurological disorder that can result in disability and death, The disease, caused by depletion of thiamine (vitamin B1) resources, is characterized by confused mental state, unsteady gait, and vision issues. It can be difficult to diagnose but is easily treated in early stages and irreversible in later stages.
- MPNforum Magazine (www.mpnforum.com) is an international on-line publication serving the myeloproliferative neoplasm patient, caregiver,and healthcare provider communities. A not for profit collective effort of the MPN community, MPNforum, founded in 2011, also publishes the MPN Quarterly Journal.www.mpnjournal.org
- Myelofibrosis is a myeloproliferative neoplasm, a rare blood cancer in which fibrosis of the bone marrow capsule can lead to blood production in distant organs, reduced hematopoiesis, severely restricted quality of life and reduced longevity.
Comments on: "Patient Safety Report" (4)
Thanks for the updates. I am curious if the Vitamin B1 deficiency caused by this drug has been seen with other Jak-2 drugs? I’ve been on Cytopia for a few years. Any comments? Thanks, Ron
Thank you, Zhen for keeping us informed. Clearly, there is a serious ethics issue here. We are empowered to partner with our medical team and I, for one, cannot partner with those I do not trust, which begs the question, “who can you trust?”
Brilliant report delving into the facts and not the fiction.
Well done Zhen and the new panel, great work.
I hope this alerts the FDA to do something regarding Sanofi for hiding the truth and causing damage to patients who are trying to help them discover the cure for MF.
I hope they are going to compensate the patients who withstood this trial as it could have killed them all.
As you say in this report had people known about W.E. and the S.A.E. they may not have entered their trial.
Good luck on this and I hope this can make a difference to future drug trials.
On the one hand they cannot test new drugs without us enrolling in clinical trials. On the other hand, who wants to enroll in a clinical trial if they are not going to be more careful?