It's not been a great day for Germany. First, they lost to Serbia in the footy. Then German pharmaceutical company Boehringer Ingelheim suffered an equally vexing setback after their allegedly libido-boosting new drug,flibanserin, failed to get approval to be sold in the US.
The FDA panel's unanimous decision was no surprise to anyone who read their briefing report which came a few days ago (here) as it was pretty scathing about the strength of the evidence that Boehringer submitted in support of the drug's efficacy. Take this bit (from page 38)
Although the two North American trials that used the flibanserin 100 mg dose showed a statistically significant difference between flibanserin and placebo for the endpoint of Sexually Satisfying Events, they both failed to demonstrate a statistically significant improvement on the co-primary endpoint of sexual desire. Therefore, neither study met the agreed-upon criteria for success in establishing the efficacy of flibanserin for the treatment of Hypoactive Sexual Desire Disorder (HSDD). At issue and a major concern of the Division are the following findings:
Ouch. Basically, the FDA concluded that as an aphrodisiac flibanserin doesn't work very well, if at all, and hence it can't be considered an efficacious treatment. For more background on flibanserin see my old post here and more recently Petra Boynton's excellentcoverage. But what was flibanserin supposed to treat in the first place? Something called "hypoactive sexual desire disorder" (HSDD). What is hypoactive sexual desi...oh, hang on. I think I can work it out. It's a disorder where you have hypoactive sexual desire. The clue is in the name. The truth is that HSDD is nothing more than its name. In fact, the word "disorder" is superfluous, and "hypoactive" is needlessly technical. HSDD is simply a fancy term for "low sexual desire." As such, it is wrong to say that HSDD doesn't exist - clearly some people do have low sexual desire, and some of them (though not all) would prefer to have more. But giving it a fancy name and calling it a disorder is misleading: it gives the impression of depth (i.e. that this is some kind of medical illness) when in fact it is simply describing a surface phenomena, like saying "I'm bored" or "I'm tired". Psychiatry - or more specifically the DSM-IV textbook of the American Psychiatric Association - is chock full of these the-clue-is-in-the-name disorders. Essentially, if the symptoms of the condition are simply summarized in the name, it's almost certainly of this type. You have "Generalized Anxiety Disorder" if you're... generally anxious. According to the next DSM-5, your kid will have "Temper Regulation Disorder with Dysphoria" if... oh, guess. Not all psychiatric disorders are like this though. The word "Schizophrenia" is a name, in that it refers to something which isn't defined by the name itself. "Schizophrenia" describes a cluster of quite diverse symptoms that are not contained in the name (and indeed if you take the name literally, you would end up with the wrong idea of what schizophrenia refers to.) Likewise for "Bipolar Disorder" and, to some extent, "Depression". "Schizophrenia" and "Depression" are names for groups of symptoms which tend to go together and saying that someone has "Depression" is meant to tell you several different things about them - e.g. that they have low mood, certain kinds of sleep disturbance and appetite disturbance, etc. In fact not every patient shows all of symptoms, all of the time, but most people show most of them. So to diagnose someone with, say, schizophrenia, on the basis that, say, they believe an alien is controlling their thoughts through a radio in their head, is to assert something. The diagnosis of schizophrenia might be correct, or it might be wrong e.g. they could in fact be bipolar, or the alien radio could be a culturally based belief, or they might even be right. But if you "diagnose" someone with HSDD, you cannot be wrong - assuming they have low sexual desire, which is the only possible reason you would make that "diagnosis" in the first place. HSDD is just a re-description of the complaint. Yet it also smuggles in the implication that behind the complaint is a medical problem which could be treated with drugs. Maybe there is. Maybe there isn't. We just don't know. HSDD doesn't appear to be treatable with flibanserin. But then, maybe that's because it's not a medical issue at all in most cases.
The trials did not show a statistically significant difference for the co-primary endpoint, the eDiary sexual desire score.
The Applicant’s request to use the FSFI [a questionnaire] desire items as the alternative instrument to evaluate the co-primary endpoint of sexual desire is not statistically justified and, in fact, was not supported by exploratory data from Study 511.77, which also failed to demonstrate a statistically significant treatment benefit on desire using the FSFI desire items.
The responder rates on the important efficacy endpoints for the flibanserin-treated subjects, intended to demonstrate the clinical meaningfulness, are only 3-15% greater than those in the placebo arm.
There were many significant medical and medication exclusion criteria for the efficacy trials, so it is not clear whether the safety and efficacy data from these trials are generalizable to the target population for the drug.
