Le Figaro has more details – leaked ones, apparently – on that recent clinical trial disaster in France. Translating, I have it as this (note that the ANSM is the Agence Nationale de sécurité du Médicament, the French equivalent of the FDA):
It is understood that the patients in the hospitalized group have brain damage in an unexpected area. But which one? Asked about this crucial point, the director of the ANSM said, grudgingly, “At the base of the skull.” True, but when pressed, the reply is just “Medical secrecy.” According to our information, this is the hippocampus and pons in the heart of the brain. We understand now the concern expressed at the press conference on 15 January by Professor Gilles Edan, Head of Neuroscience pole of Rennes University Hospital. He explained: “Three people already have symptoms severe enough to fear an irreversible disability but no definitive prognosis can be made.” Today the five patients seem out of danger (tirés d’affaire).
I hadn’t heard that last part – I have some difficulty figuring out how you can have damage in either the hippocampus or pons and be “out of danger”, unless that’s just in the sense of “not in immediate danger of dying”, but we’ll see what details emerge. And then there’s this:
Moreover, in private, the investigative committee (CSST) believes that the protocol should not have given large doses to five people simultaneously. . .Finally, the so-called pre-clinical data, that is to say tests on animals, could well conceal explosive information. Dog studies on the molecule led to the death of several of them, according to the same source. This is information “of considerable importance. This can be a real warning signal,” said Prof. Daniele Piomelli, professor of neurobiology and pharmacology at the University of California at Irvine. But the real details are always hidden.
Deaths in dog tox are indeed very bad news, and warrant great caution in continuing to humans. As Le Figaro notes, though, we don’t know what these animals actually died of. No matter what, though, that can be a show-stopper, and normally you’d only make it on to human clinical trials, if at all, after a very thorough examination of why the animals died and why you don’t expect it to happen in the clinic. Your reasons had better be extremely convincing. The usual rule is “Drugs kill dogs and dogs kill drugs”, so making an exception to that is not to be done lightly. This, one assumes is what the investigative committee is looking into – whether this drug should have gone into human subjects at all, given the preclinical signs. . .
Update: more at The Guardian.
Update 2: not everyone’s quite as worked up about the dog death incidents as I am, pointing out (quite correctly) that we don’t know the dose and the multiple of the toxic dose over the expected effective dose. All true, but in my own experience, a dog’s death in tox has always slowed things down a great deal, as people tried to figure out just what caused it and what level of sensitivity humans would be expected to display from that mechanism. We also, frustratingly, don’t know the actual cause of death – cardiovascular is the usual suspect in a dog tox run, because as a species they’re quite sensitive to some of those mechanisms. In that case, it would be a slowdown, but not a killer for a drug candidate, because toxicologists, although concerned with such an event, feel as if they have a better handle on it. We need more details!