The Impatient Addyi Advocate: Flibanserin Pitch by Possible Placebo Patient!

 

Dr. E in the thick of it as usual, with Greenberg and Striecher on C-SPAN at 4:30 yesterday morning.

Dr. E in the thick of it as usual, with Greenberg and Striecher on C-SPAN at 4:30 yesterday morning.

“The first prescription drug to enhance women’s sexual drive…”

…was the opener for Andrew Pollack’s charitable coverage of a blunder the Food Drug Administration (FDA) can never live down. The FDA just approved Sprout Pharmaceuticals’ flibanserin, trade name Addyi. The drug does not enhance a woman’s sexual drive. It’s not even supposed to, if you acknowledge a distinction between drive and desire. I do know of Mr. Pollack’s fine body of work. “FDA Approves Addyi, a Libido Pill for Women” doesn’t enlarge it.

Even-handedness is generally good, but when an FDA assertion boils down to…

fda

…even-handedness requires an explanation. Mr. Pollack failed to disparage a controversial and abandoned diagnosis, hypoactive sexual desire disorder, and was equally tolerant of the controversial new drug. Tolerance seems decent, and it would be if a flibanserin weren’t in the same obscure drug class as the antidepressant Valdoxan (agomelatine). Reading the remarks of people who’ve tried Valdoxan, which is not available in the US, makes me wonder why it is available anywhere. It can be prescribed in the EU, Australia and Canada. It does nothing resoundingly for some, good things ever so timorously for others, and bad things like it really means them for the rest. Novartis bought the right to market the pills in the US, but phase III trials went badly and they threw in the towel.

Here are some comments about flibanserin’s chemical cousin, Valdoxan:

Valdoxan sleep reports

By the way, Valdoxan’s big selling point is that it doesn’t interfere with sleep.

I can’t work up any enthusiasm for flibanserin. The odds of getting off on it without incident are not impressive. Because it was designed along the lines of an antidepressant, it might have a painful withdrawal period after the user gives up on it. What are the odds of getting off of it without incident? Where are the results of “Flibanserin Randomized Withdrawal Trial in Pre-menopausal Women“?

Some wonder how flibanserin works, or more accurately, how it “works.” That’s a pretty corny question to be asking in 2015. Everyone knows that the proposed mechanism of action of flibanserin involves regulation of several brain chemicals that may affect sexual desire, although the exact mechanism is not known. So says Sprout in a brand-new Drugs.com entry, but who cares? One proposed mechanism is as good as the next for an FDA-approved psychotropic drug. Sprout could have said it bores holes in the hippocampus and fills them with radioactive fluoride. Any scholar bold enough to hint that that sounded slightly sub-optimal would have been labeled anti-woman and Timothy-Hunt-ed out of academia.

women_pos

EXPERTS of EVERY STRIPE

Pollack presented uncritical assessments from inexpert or perversely motivated Addyi adherents, balanced with only the weakest of criticisms from well-qualified detractors who’ve made more substantial remarks elsewhere. Three of the latter were lumped into a paragraph toward the end of his piece, with the most damning remark left unexplained. Here’s the critics’ ghetto, with my remarks in brackets:

One letter, written by Dr. Tiefer of N.Y.U. and signed by about 100 others, said it was “absurd” to expect that young women taking Addyi would refrain from drinking alcohol.

[It is absurd to expect that, but Tiefer has also said she doubts HSDD is a physical condition and proposes non-drug ways of helping people with the symptoms of HSDD.]

Another, by the PharmedOut project at Georgetown University Medical Center, which also had more than 100 signatures, said that the “unprecedented and unwarranted manufacturer-funded public relations campaign” may have confused the advisory committee members.

[That sounds purely political, and ignores PharmedOut’s detailed critique of the drug on medical grounds. It’s easy to find on their web site, where you can also read Dr. Tiefer’s letter.]

A third letter, from sex researchers in the Netherlands and Belgium, said the drug was based on the mistaken notion that lack of spontaneous sexual desire, absent stimuli, was abnormal.

[Please steady yourself. Those Europeans are right.]

WHAT DOES A WOMAN WANT TO WANT?

The supposed physical ailment (let’s go with “chemical imbalance”) that this drug [doesn’t] cure treat address is not the failure to become aroused when someone strokes your neck or says you look awfully good in those jeans. Hypoactive sexual desire disorder (HSDD), last seen in DSM-IV, is the failure to have sexual fantasies and dreams regularly, along with some specified concomitants. Here’s how the FDA’s Dr. Janet Woodcock, a senior official, tip-toed around the the markedly non-disorder-like HSDD in the context of the flibanserin flub:

Today’s approval provides women distressed by their low sexual desire with an approved treatment option.

It’s not low sex drive. It’s not low sexual desire. It’s being distressed by low sexual desire, and a bit more, which Dr. Woodcock left out: interpersonal difficulty. Indeed, per DSM-IV, “[t]he disturbance causes marked distress or interpersonal difficulty.” Flibanserin can be prescribed for a feeling you don’t have, if someone else wishes you had it.

HSDD’s symptoms were not enough on their own to persist as a disorder, but paired with the understandably distressing inability to become physically aroused, are subsumed in female sexual interest/arousal disorder, which made its debut in 2013’s DSM-5. The symptoms found  a home, but HSDD is history.Why not take a drug for a disorder whose symptoms appear in your husband, and which was kicked to the curb by a professional organization that’s ordinarily only too happy to have another diagnosis its members can treat with 10 minute med-checks in perpetuity?

THE ART OF THE SPIEL

To his credit, Pollack did not quote the flibanserin clinical trial participant who sought and got a lot of publicity for her story of success. She made her plaint for the FDA and took her show on the road, and has been interviewed, written about, written, launched a blog and started a business that has something to do with women and sex. That she did not know whether she was on the drug or the placebo during or after the trial didn’t stifle her enthusiasm, we learn from a 2015 Buzzfeed piece:

[She] didn’t know (and still doesn’t know) whether the pills she popped every night were the real thing or a placebo, even though she was invited to check once the trial was over. Given her total turnaround, she decided she didn’t need to check: She was convinced they were flibanserin.

That was published in February. Five mothers earlier, at an FDA-hosted pow-wow called “Female Sexual Dysfunction: Patient-Focused Drug Development Public Meeting,” the patient informed the professional panel and her fellow sufferers that she was treated with flibanserin, and that it definitely elevated the whole level of intimacy in her marriage. Not only that, but once she stopped taking flibanserin, “it returned to normal and unfortunately the whole burden falls in his shoes.” (Transcripts for Part 1 and Part 2 of the Oct 27 session are here and here. You can find out more about what happened to her husband’s shoes on page 80.)

We are always told that this enthusiast was a sales rep. I always think of laser printer supplies when I hear “sales rep,” which is so uninteresting that I stop thinking about the person at all. I made a mistake in this case. Until June, she was a sales rep for Noven. Not Noven, the French interactive agency with an English slogan, and not Noven, the Colorado investment advisors who would do well to get in touch with their French name-fellow for a web site update…

 

noven_etc

Noven Pharmaceuticals.

[I had so much to say about Noven’s products and marketing that I moved it to a new post, Starve, or Sell Mind-wrecking Poisons? ]

You’d have to be more fond of money than people to work for Noven and push the junk they make, in my opinion. Has money been a motivation for the motor-mouth matron who apparently can’t say enough about her need to take pills in order to contemplate sex with her husband? I don’t know.

I do know that her LinkedIn profile shows a switch from Noven to self [un]employment in June, 2015, the month she addressed the FDA committee that voted to recommend that the FDA approve flibanserin at its August gabfest, which it did. And there’s this item on her résumé on indeed.com:

amanda_advocate_job

In addition to advocating and spokes-personing, she founded and directs SHE 4 Women, an organization dedicated to “the promotion of women’s sexual health excellence and equality.” Her blog, SHE (Sexual Health Equality) for Women lets us learn more than I ever wanted to know about the sufferings of the HSDD-afflicted. In her own words, colors, and font choice:

amandaswordsshorter
I was unable to form big words after I came upon her LinkedIn profile and learned that for many years, she’d sold drugs for a living. I shot a link with a message like “Dude, whoa. Drug rep” over to a clear-headed Twitterer who’s on top of the flibanserin story and well worth a follow, @PhDefunct. She had the presence of mind to search the web for “SHE 4 Women.” Other than the blog, no results: A flibanserin clinical trial of a business.

shehealth
APPEALS TO AUTHORITY; VOLUME DISCOUNT

Pollack found two credentialed experts who, remarkably, were not railing against the FDA’s decision, but nor were they all in for Addyi. Given the syncope side effect, faint praise from those in the know is to be expected, but he didn’t even get that. There’s a positive tone to this MD’s statement…

Dr. Lauren Streicher, associate professor of clinical obstetrics and gynecology at Northwestern University, said she sensed great interest for a drug like Addyi among her patients. She said the drug’s availability would encourage many women to talk to doctors about their sexual problems for the first time.

lovedog…but it’s not about the drug. Great interest in a drug like Addyi, sensed by Dr. Streicher, you say? And such outcome. Many women talking to their doctors. Streicher’s a team player, no doubt about it. But if the drug worked, her patients would be talking to bankers, plumbers, laser printer supply salesmen and “handsome strangers,” too.

Speaking for the FDA, Janet Woodcock said the FDA is

committed to supporting the development of safe and effective treatments for female sexual dysfunction.

I hope they get on top of that soon, because Addyi doesn’t fill the bill. Not only is it unsafe and ineffective, it’s not for a sexual dysfunction. It’s for a mental disorder in the dust-binned DSM-IV. Part of the problem in this whole C-section of justice was that, as @PhDefunct is fond of mentioning, flibanserin was evaluated the by FDA’s Bone, Reproductive and Urologic Drugs Advisory Committee, whose members might not be appropriately cynical about the utility of retrospective self-reports of subjective phenomena or the validity of DSM disorders. They might not know that when the American Psychiatric Association chucks a diagnosis, there’s a good chance it should stay chucked.irwinsexdoc

We know Sprout was in it for the money, and though it’s unforgivable, it’s forgettable. In contrast, doctors are our first line of defense against bad drugs, but too often they are co-opted by money interests, especially when those line up with their own points of view, but sometimes just because they’re more fond of money more than people. Pollack included two ill-boding statements by MDs that validate PharmedOut’s and Tiefer’s misgivings about flibanserin in the wild:

Dr. Streicher said that although the drug was approved for premenopausal women only, she “absolutely” would prescribe it for postmenopausal women as well.

Stroke. Seizure. Tachycardia. Oh well! And then…

Dr. Irwin Goldstein, a sex-medicine doctor in San Diego with a “provision staff” appointment at UCSD on his C.V., who has been a consultant to Sprout, said he would not necessarily withhold the drug from casual drinkers. Some women might find the risk of side effects acceptable if their relationships are in jeopardy because of a lack of desire, he said. “That’s a risk, too.”

Jesus Joseph and Mary. Do they snack on kittens between meals with drug reps?

cancers“This is the biggest breakthrough for women’s sexual health since the pill,” declared Sally Greenberg, executive director of the National Consumers League (NCL). Sally was a poli-sci major at Antioch College. Her arch-liberal arts pedigree excuses a head-in-the-sandy belief in the health-enhancing properties of hormonal birth control. Sure, it’s been found to reduce the rates of ovarian and endometrial cancers. There’s a downside, too. Beyond stroke and weight gain, ten years on the pill quadruples a woman’s likelihood of developing cervical cancer, and that’s not all. Birth control pill use was compared in 1102 breast cancer patients and 21,952 healthy women in a 2014 study. Use of birth control pills other than low-dose estrogen formulations was seen to double and even triple the odds of a breast cancer diagnosis, and quickly, within a year of use. Nine percent failure rate, too, says the Centers for Disease Control.

Pollack lets slip later on that Sprout, Addyi’s maker, donated to Greenberg’s NCL. That might be why she left out the thing about women on the pill experiencing less arousal, fewer orgasms, difficulties with lubrication, decreased pleasure and less frequent sex. (How long until there’s a birth control/Addyi combo product? 😞)

Greenberg’s organization sounds all right but there’s something screwy going on. They have two web sites, www.nclnet.org and natlconsumersleague.org. They’re different in layout but not markedly different in content at first glance. I don’t what that means, but it’s screwy. Second glance led me to their annual report (on just one of the sites), and a list of donors who’d given $1000 or more. Nearly every drug company I could think of was listed: Allergan, Amgen, AstraZeneca, Johnson & Johnson, Lilly, Merck, Macneil, Procter & Gamble, Sanofi, Teva, not to mention three pharmaceutical trade groups. Perturbing, but the priming meant I didn’t freak out noisily when I wandered into “Take Your Meds.” However, another minute on that site and I’d have taken this guy’s meds.

meds

 


 

DRUGS AND MONEY, MONEY AND DRUGS

“The big question now is how many people will use Addyi”

Pollack wound up his introduction thus, catching his breath before going on to wind up his readers with a neutratorial that’s no credit to America’s newspaper of record.

I don’t think it’s such a big question. It’s probably overdetermined. Plenty of people have lousy sex lives and plenty of people believe the FDA would not approve an ineffective, unsafe drug. The medicalising of womens’ sex lives is bound to pick up some of the slack as the Prozac era comes to an end without anything like a blockbuster antidepressant in years to keep the cash coming in. Alongside obesity-as-a-brain disease and You Need Speed® (expanding the indications for stimulants like methylphenidate, detroamphetamine, and methamphetamine, i.e. Ritalin, Adderall, and Desoxyn) the seven-year itch should prove lucrative.

palatin6“Signs point to yes” for sex drugs for women, and Sprout has company in believing that. I  just found out serendipitously the value of the search term “HSDD.” My clumsily-typed search for DSM-IV’s description of HSDD was supposed to read “dsm-iv hsdd” but came out as depicted in the screen shot to the right, top: “cdm-ix hsdd”. Palatin is paying for keyword “HSDD” even if it looks like a web-searcher lacks dishwasher parts or mastery of Roman numerals, not spontaneous sexual desire. Investment in search keywords is usually more discriminating. “Family mileage ford” brings up ads for Ford automobiles, while “kayak mileage ford” brings up directions to river fords useful to kayakers.

Why is Palatin casting that wide net? Because they’re in Stage III trials of subcutaneous Bremelanotide, a drug that does seem to be an aphrodisiac, if Wikipedia can be trusted (just this once).

Why Bremelanotide trials instead of, say, a cure for toenail fungus? One that works, I mean. Because they, like Sprout (and Valeant, as we’ll soon see), believe there’s money in it.

Why now? Maybe because anti-depressants impair sexual functioning in a good chunk of the 21% of American women over age 21 who reportedly take them. Problems can be as straightforward and disabling as outright lack of sensation where it counts, but might include sexual inhibition due to changes in appearance. Hair loss, acne, and unprecedented weight gain are among antidepressants’ side effects. Lookee here: 2015 … Increased Body Mass Index in women on selective serotonin re-uptake inhibitors, but not those on tricyclic antidepressants or nothing, and not in men. Imagine the strife when she correctly attributes her weight gain to the SSRI she’s on, and he points out that he’s on it too, and hasn’t gained an ounce. Throw in the effect of birth control pills on sexuality and you’ve got a substantial customer base of naive or gullible women willing to take a pill to solve a problem they’ve unwittingly caused themselves by taking pills they had reason to believe are salutary and benign.

So, the answer to the question Andrew Pollack posed is “a lot.”

The bigger question is why would anyone want to use Addyi? Partly because articles like Mr. Pollack’s don’t give it the thrashing it deserves, and partly because their doctors may not give a damn about their health.

I hope the experienced and accoladed Andrew Pollack will tolerate a bottom-feeding blogger’s ex post facto egress-emending, now that the equine has exited.

Mr. Pollack should have checked ProPublica’s Dollars for Docs before pressing send. All journalists should. It turns out Dr. Goldstein of San Diego was in the game for a fat $120,000 from August 2013 to the end of 2014. Don’t look all shocked yet, unless your eyes open wider than that. Dr. Lauren Streicher pulled in an impressive $229,000 for 17 months of jaw-waggery, about $13,500 a month. Her most lucrative handler, with the most individual payments and the most travel, enriched her by $61,636, almost all of it for hawking (Please cover your eyes for a sec … wait … Okay, now you can open them. Look: Brisdelle!)

Brisdelle, by Noven.

Noven, where the patient/enthusiast used to perch.

boughtusadrone
I’d instructed my broker to purchase 50,000 shares on my behalf when Sprout IPOed, but within days of FDA approval, cynical hucksters Cindy and Robert Whitehead, Sprout’s owners, indicated there was something worth more to them than woman’s sexual health, namely, the $1,000,000,000 in cash they took from Valeant Pharmaceuticals International in exchange for their little charade. #YesOneBillion.


Postscript

 

jellieterrierThe first company to make a killing on a sex drug for women did it by getting rid of it. That might or might not tell us what lies ahead. 

Lisa Rosenbaum can reconnect the dots in this ugly mess; she’s obviously got the temperament of a Staffordshire terrier, whereas I’m set up more like an Aurelia aurita, or Chrysaora hysoscella, as my people are sometimes called.

I’m am grateful I don’t want to want something, and that no one who wants me (N=1) wants me to want anything I don’t want.

Related News

If you missed Dr. Edie with Greenberg and Streicher on 60 Minutes last week, it’s on YouTube with about a million hits and 30,000 shares. Unfortunately, Dr. Evie was fresh from her daily mud-bath. Streicher’s an OB-GYN out of University of Chicago; what hasn’t she seen? Greenberg, on the other hand, threw up.

PSA: If you’d like to help a community of people who believe the drug should not have been approved, there’s a petition still collecting signatures at Change.org. At the moment they are 869 858 847 838  833  818  813  874 760 shy of their goal of 2500. Clickez-vous the banner to get to the page.

antiflibpettition


 

4 Comments

Add a Comment