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Wednesday, November 18, 2009

Hard to Get Excited about BI's Flibanserin

You might have missed the 12th Congress of the European Society for Sexual Medicine in Lyon, France, this week. If you did, US Phase III results for Boehringer Ingelheim's flibanserin might have passed you by, too.

The drug--a serotonin 5-HT1A receptor agonist, 5-HT2A antagonist and partial dopamine agonist--is in development for Hypoactive Sexual Desire Disorder among pre-menopausal women. The condition is characterized by a decrease in or lack of sexual desire "that causes distress to the patient, may put a strain on relationships, and is not due to the effects of a substance....or another medical condition."

So we're not going to downplay the importance of this condition, despite suspecting that many might be surprised to learn that it is one--including most women suffering from it, according to Dr. Sheryl Kingsberg of University Hospitals Case Medical Center in Cleveland, Ohio. (Prevalence may, according to Kingsberg, be as high as one-in-ten.) We won't downplay it, even while predicting it will provide more fodder, if ever there was fodder, for industry critics seeking evidence that pharma invents diseases.

But we can't help raise some red flags when it comes to the likelihood of getting this drug past the regulators (let alone the reimbursers) for HSDD. Aside from whether the disease exists (and granted, we mustn't forget that depression was ignored/denied for many years), there's the issue of highly-subjective scoring and accounts in the trials. (How else to run a study measuring how many 'satisfying sexual events' (SSEs, another new acronym for you) a woman has, and just how satisfying they are, aside from asking her to write it into her e-diary?)

Then there's the issue that the pooled data from these two, six-month Phase III trials among a total of over 1,300 pre-menopausal women wasn't exactly compelling (at least to our untrained eye...): women in the highest-dose flibanserin group enjoyed an increase of only about one SSE per month compared to those on placebo. (And it doesn't appear from the release that there was even a statistically significant increase in primary endpoint SSEs in the European flibanserin trials.)

Meantime, and here's the real crunch, 15% of women in that same high-dose flibanserin arm dropped out due to side-effects (versus just 7% on placebo) which included daytime sleepiness, dizziness, fatigue, anxiety, dry mouth, nausea and insomnia. Not to worry, said lead study author and professor of psychiatry and neurobehavioral sciences at the University of Virginia, Anita Clayton, MD, on a webcast announcing the results. "These are side-effects often seen with CNS-acting medications, which affect the brain. They tended to be transient."

For the women, we can only hope those discomforts were worth it for the additional SSE. As far as the regulators go, we reckon it's unlikely that they wave through a centrally-acting drug (in the same broad class as Arena's Phase III obesity candidate lorcaserin, or Sanofi Aventis' insomnia hopeful eplivanserin, which received a complete response letter in September) whose complete mechanism of action is unknown, and which leads to considerable (if not apparently too serious) side-effects, for an indication that took 20 minutes to describe on a recent webcast announcing the results. (Flibanserin is thought to affect the sexual desire/drive component of HSDD, by acting on brain neurotransmitters.)

We're not saying this drug candidate will never be approved; we're just saying we think it's unlikely to happen fast. (Fortunately, Boehringer has other, far bigger, fish to fry.)

Granted, there aren't currently any FDA-approved drugs for HSDD among pre-menopausal women, explains Anita Clayton; couples counseling is about it. And if the SSE data wasn't that exciting, women did report significantly improved sexual desire & functioning, and less distress related to low sexual desire.

image from flickr user michelle brea used under creative commons license

3 comments:

Anonymous said...

Oh my god, so much is wrong with the news about flibanserin! Thank you for pointing out the problems!

I love how the placebo group also experienced a significant improvement in their libido. They went from 2.7 SSEs (satisfying sexual events) per month to 3.7. The flibanserin group went from 2.8 to 4.5. Since 15% of the flibanserin users dropped out because of adverse reactions, it seems that the placebo is the better choice. :)

But here's a more fundamental issue: how can 10-25% of a any group be abnormal and require therapy? I would say if 10-25% of a group has a particular characteristic, then it is actually normal. By what standard are we measuring sex drive? In our hyper-sexed culture, it seems we're expecting women to want to have sex multiple times per day, and if they don't there must be something wrong with them. Well that might be the attitude of the drug company because they need a treatment-worthy condition in order to sell their drug, but they are not the best judges. Perhaps what we should do is accept that women are different from men, and one of those differences is a lower sex drive. Nothing wrong with it.

I think for most women, stress and overwork is the #1 libido killer. No pill is going to fix that.

Anonymous said...

Although the findings may not have been statistically significant, this is a well known and very disturbing condition many women suffer, especially throughout the menopause cycle. I am elated to see them moving forward with helping women feel better about their physical and intimate sexual experiences, whether it was due to placebo affect or not.

We do not have to belong to a hyper-sexual culture to want to feel the sexual desire and drive towards our partner again. This is a feeling that, due to hormones, has put many of us asking why. As much as we may be in a loving, stable relationship by that point of our lives, why do we no longer feel the desire to share that sexual contact; why is it no longer important. We may have wonderful self-esteem, feel great about who we are at this point in our lives, aging well, vibrant - and yet feel as if a huge part of us is missing - not something that can always come back thru cognitive therapy because our body just doesn't respond.

Not to get into a moral debate - but if we no longer feel the desire to share sexual intimacy with our partner, doesn't that in turn reject him? Which, in some (OK - please no debate on this), may lead for him to find a younger, more sexually willing partner?

I say thank you - and a long time coming. Looking forward to seeing more in the future.

john said...

I find the skepticism about this to be fascinating. It is interesting that in our highly sexually repressed society anything that seems to increase sexual desire or is sexual in nature is immediately poo-pooed as sick or meaningless, made-up, in our minds, due to all kinds of "other" things usually related to the persons morality or lack thereof.

The major cause of breakups in relationships is incompatible sexual desire. Lack of sexual behavior is associated with depression and why not? Sex is life-affirming, it is pleasure we can share with others. It is a blessing and when it doesn't exist it creates insecurity, depression, just plain lack of fun in life. This is not trivial. It may not be life or death but it is important, arguably very important to the happiness of many people.

This drug doesn't seem like a panacea by any means but if it helps some people and doesn't cause lasting side effects it should be approved immediately. Even if most people take it and get only a placebo level effect that is a lot more happiness in the world. Why would we be so blase about that? Why would we be so skeptical?