Saturday, August 06, 2005

Being an American shareholder can be like walking through an unmarked minefield

Merck looks like it's headed for financial ruin from the lawsuits related to failing to disclose its blcokbuster antiarthritis pain killer VIOXX caused serious heart problems. At the trial now underway newsreports indicate the company's scientists' testimony paint a picture of deception and evasiveness with respect to compliance with FDA rules.

I am not surprised because I witnessed much the same thing when I formally objected at the FDA to Procter & Gamble's attempt to license Intrinsa, the supposed female "Viagra". The FDA backed my position and refused to license the drug. I was in deep shock at the hearing by the evasive testimony of PG's scientists' testimony. Posted below is my testimony before the FDA. Lengthy but interesting. Postscript--I no longer own any pharmaceutical stocks. To hold them is to play financial Russian Roulette.

RE: Objections to Instrinsa FDA New Drug Application--(NDA) 21-769
Objector: Mark I. Klein, M.D. Board Certified Psychiatrist
Date: December 2, 2004. Meeting time 8:00 a.m. Public comments 11 a.m..
Place: Hilton Hotel, 620 Perry Parkway, Gaithersburg, MD 20877
Potential conflict of interest: I am Procter & Gambler shareholder.


In my medical and psychiatric opinion Instrinsa is the most hazardous non-narcotic drug ever presented for FDA approval. I urge it be rejected for any use, and if approved by a foreign country, banned from sale in the United States under threat of severe civil and criminal sanctions.

1. Instrinsa is an inherently UNSAFE drug which should not be approved for any use.

Instrinsa is a major threat to the health and safety of girls, non-menopausal women, pregnant women, fetuses and nursing newborns. Almost a certainty in today’s highly sexually charged cultural zeitgeist to be widely abused by non-menopausal females, adolescent girls and pregnant women exposing them to the risks of testosterone induced usually irreversible virilization. Since Instrinsa enhances libido for all women, the abuse risk is all the more heightened. The excerpt to the right from a recent New York Magazine article speaks cogently to the likelihood of Instrinsa abuse. (endnote 1)

The popular press already toots Instrinsa as the female Viagra usually without warning of the dangers to non-menopausal women, fetuses and nursing newborns. Google lists 70,020 Instrinsa listing most of which refer to the drug as the female Viagra without adding the dangers it poses to non-menopausal women, fetuses and nursing newborns.

Instrinsa is today’s potential Thalidomide. Pregnant and nursing mothers improperly taking Instrinsa risk virilization injuries to the fetus and nursing infants.

Every prescription testosterone product sold in the United States is contraindicated in pregnancy, for nursing mothers, and in most cases contraindicated for use in females.
Proctor and Gamble has made no showing Instrinsa would qualify for exemption from regular testosterone labeling. In fact, in Instrinsa studies underlying the current application indicate that some subjects manifested signs of testosterone toxicity even in very low doses.
Female testosterone toxicity causes virilizing effects such as irreversible hair loss, acne, enlarged clitoris, hirsutism, deepened voice, and impaired glucose utilization. (see endnote 3) Breast size may decrease; vaginal mucosa may atrophy; menstruation may change or stop, and increased libido. In prepubertal and pubertal users, bony epiphyses may close prematurely, possibly decreasing final height. Hypertension, increased low density lipoprotein (LDL) cholesterol, and decreased high density lipoprotein (HDL) cholesterol may increase cardiovascular risk.

Psychologic effects include wide and erratic mood swings, irrational behavior, increased aggressiveness ("steroid rage"), irritability, depression, and dependency.
Fetuses with testosterone toxicity can experience congenital developmental abnormalities. Male fetuses and nursing newborns may develop gynecomastia, testicular atrophy, and eventually severely reduced or absent sperm. For testosterone affected female fetuses ambiguous genitalia.

The risk of Instrinsa abuse undermines America’s efforts to discourage the illegal use of anabolic steroids by athletes. In this country, anabolic steroid abuse is 6 to 11% among high-school-aged males, including an unexpected number of nonathletes, and about 2.5% among high-school-aged females presumably to enhance libido. There is a thriving black-market for such drugs. Instrinsa would be a very profitable welcome addition to the pharmacopoeia of drug peddlers’ preying on our children.

Easy access to Instrinsa would enable athletes, particularly males, to easily obtain androgens. Nothing would stop such boys and men from using multiple patches simultaneously to get the end point response they seek along with testosterone’s debilitating side effects, e.g. impaired glucose utilization, disruption of pituitary adrenal axis regulation, gynecomastia, decreased HDL, testicular atrophy, azoospermia, and personality changes like increased aggression. Used by prepubertal and pubertal boys bony epiphyses may close prematurely, possibly decreasing final height.

There is no conceivable marketing scheme to avoid widespread inappropriate use. Nowadays abusers could easily obtain Instrinsa once approved via internet pharmacy sites, overseas outlets, unscrupulous physicians out for a quick buck writing “off label” prescriptions, and from a black market which would undoubtedly quickly appear. (see endnote 5)
Marketing Instrinsa would eventually likely result is a wave of litigation by injured women and children which at the very least seriously damage the company’s reputation and balance sheet, wreck shareholder value and conceivably throw PG into bankruptcy.

Licensing Instrinsa could eventually discredit the FDA’s drug approval system in the same way Thalidomide did about 40 years ago by creating the public perception the agency is the big pharmaceutical companies’ rubber stamp.

2. The results of Instrinsa’s efficacy studies presented to the FDA are insufficient to prove efficacy.

Proctor and Gamble incorrectly believes just a statistically significant improvement in the sexual satisfaction of post menopausal women is a satisfactory end point to show efficacy. (see endnote 4) That assumption demonstrates a breathtaking lack of understanding of the sexuality of post menopausal women, particularly those married or in long term, committed loving relationships. Procter and Gamble’s Instrinsa application replies upon very short duration studies involving women in self described good relationships.

In recent years the number of divorces in long married couples has dramatically increased with the majority initiated by women. The key factors involved are sharply increasing longevity for both sexes and contemporary divorce law financial incentives for women to leave, e.g., community property, alimony, strictly enforced statutory child support orders predicated on spousal earnings and today’s very anti-male cultural zeitgeist emphasizing the overarching value for women to seek personal fulfillment. (see endnote 6)

Prolonged longevity increases the likelihood long married older couples will lose sexual interest in each other. Among the reasons they remain together include maintaining their relationships as affectionate, loving friends, prefer divorce but can’t afford to maintain separate households, or stay together for the sake of the children. Unilateral rekindling of sexual desire in such precarious marriages might trigger the collapse of the relationship.
Divorce statistics show marital stability for postmenopausal women, Instrinsa’s target group, is very precarious. Hence in determining Instrinsa’s efficacy the FDA must give equal weight to the social VALUE implications of allowing its use. (see endnote 6)

As a psychiatrist, I believe the future of American marriage is very dismal indeed. Marriages primarily predicated in the rush of romantic feelings have little chance for survival in today’s climate of no fault divorce and financial golden parachute child support and property division divorce settlements. (see endnote 7) Absent making every effort to stabilize American marriage more and more marriages will fail leaving emotionally shattered children in their wake.
November’s election results on gay marriage initiatives demonstrated voters overwhelmingly consider marriage a fundamental American moral and social value. Hence all the more reason the FDA must consider as a paramount variable Instrinsa’s likely destructive effects on marital stability in the assessment of the drug’s efficacy.

In conclusion I believe Instrinsa is the most hazardous non-narcotic drug ever presented for FDA approval. I urge it be rejected for any use, and if approved by a foreign country, banned from sale in the United States under threat of severe civil and criminal sanctions.
Respectfully submitted,

E-mail to Proctor & Gamble CEO Lafley & board member Robert Story
Mon, 1 Nov 2004 14:03:14 -0800 (PST)
"MARK KLEIN, M.D." View Contact Details
Better to ditch Instrinsa & take a writedown than face endless litigation
Top of Form 1
&& &&&&&
Bottom of Form 1
This morning sold my 3300 Merck shares plus those in trust and custodial accounts I manage. Don't think Merck's ultimate Vioxx liability is that great but mass tort litigation becomes a terrible distraction for management. Can easily see Merck's directors, officers, scientists, and administrators spending the remainder of their careers in depositions, answering interrogatories, and spending endless hours in conferences discussing the case. Do you really want plaintiffs' counsel rifling through PG files, e-mails, etc?
Got some insight into the toll all that has on companies and directors when I formally appeared as shareholder objector to a Bank of America proposed class action settlement. Really a total bullshit case. The class sued the directors personally as well as the bank. In hallway conversations before court started with defense counsel I learned the suit, already then about 5 years old, was a terrible emotional drain on the directors and a big distraction for management. I objected to the $5 million in attorneys' fees B of A wanted to pay in my opinion to buy off plaintiffs' counsel. In the settlement the plaintiffs received ZERO dollars. The trial court level hearings last several months! The trial judge approved the fees but other objectors appealed. The appellate court won't hear oral arguments until next year at the earliest. In the meanwhile the lawyers' meters are running. Plaintiffs’ counsel are demanding more dough, and undoubtedly defense counsel is secure knowing junior's Harvard tuition this semester and many more to come are covered!
I think Proctor & Gamble is a terrific company. Believe me I wouldn't have invested if I didn't think that. You just made a MISTAKE with Instrinsa. Given our balance sheet a write down would be no big deal. Better a few red faces than spoiling the company's future. Time for PG to move on.
I certainly have other things to do including among other things not spending a grand to come to the hearing for the privilege of addressing the FDA for 2-5 minutes. But I'll come if necessary. In a situation like this you'll find me a very persistent, determined adversary.
Mark Klein, M.D.
1-I postulate such manic, often loveless, pubescent and adolescent sexual behavior reflects the failure to develop neuropsychological structures necessary for deep, lasting emotional attachments by children daycare raised from infancy, or were very young when their parents divorced. Such developmental neuropsychological failures may help explain today’s 50% plus divorce rate, low marriage rates, and about 50% of marrieds of both sexes admitting to adultery.
Regardless of the presence, or absence, of postulated neurophysiological deficits, children’s loveless sexual acting out reflects a disturbed emotional mixture of identification and simultaneous competition with divorced parents reprising adolescence when reentering the dating scene.
2.-(New York Magazine 5/10.04) Intelligencer Briefing
The Paris Hilton Effect
Daphne Merkin on the new video that’s been making the private-school rounds—and the culture of teenage exhibitionism. By Daphne Merkin
To be a teenager, as many of us can still painfully recall decades after the fact, is to live in a nearly constant state of lonely mortification—and an almost equally constant state of intense socialization, otherwise known as gossip. Although the endless trading in personal details helps to spread the mortification around, the self-doubt that comes with adolescence is peculiarly resilient: Am I pretty enough? Normal enough? Popular enough? Thin enough? And, most important, in this Age of Britney: Am I hot enough? That one dopey word—hot—is my 14-year-old daughter’s highest term of regard for a peer, male or female. It’s not clear to me that she knows exactly what she means by this, but it has something to do with a pungent essence—an eau de sex—that she imagines wafts off those kids she considers to be the lucky ones.
In the latest instance of a teenager attempting to convey her hotness factor, a Horace Mann eighth-grader used a digital camera to tape herself masturbating and simulating oral sex, then e-mailed the gawkily explicit video—which resembles an audition for a pedophiliac porn film—to a male classmate she had a crush on. The boy in question chivalrously rushed the three-minute clip onto the Web, and its contents quickly made the private-school circuit.
3- America can ‘t afford another new source for diabetes. A sign the current obesity driven diabetes epidemic is out of control is amongst the leading advertisers on Fox News are diabetic testing suppliers. Today’s obesity epidemic is the result of too few adults and children regularly eating home cooked, balanced, portion controlled meals. Restaurant, takeout and fast foods are usually atrociously overloaded with fats and carbohydrates with little protein. The rate of increase in adult and childhood obesity over the past 30 years closely tracks in the steady rise in the number of mothers entering the fulltime workforce.
4-Before the DEA mandated “triplicate” prescription blanks for most narcotics, many physicians did a thriving business knowingly supplying addicts with drugs. In the Vietnam War era many physicians made huge sums by writing fraudulent letters to draft boards to convert young men likely 1A eligible for the draft into 4Fs. Unscrupulous, greedy, conscienceless physician behavior will always be with us.
5-The widespread abuse of Viagra-type drugs by younger men, unlikely to have ED, speaks to the complexities of human sexuality. Like what will happen with Instrinsa, there are thriving black and gray markets illegally selling authentic and counterfeit Viagra type drugs.
The reason so many young men take Viagra type drugs is widespread “Portnoy‘s” syndrome. In “Portnoy’s Complaint’ Roth’s world class lothario Alexander Portnoy couldn’t get an erection with the tough Israeli girl soldier. Today’s sexually aggressive women create in guys what we called castration anxiety in my med school days.
The psychodynamics of Viagra-type drug commercials are very informative re today’s sexual zeitgeist. Contrast Viagra and Cialis commercials. Re the Viagra commercial, I associate to the celebrating men dancing in the street with the thought finally having successful intercourse get their wives, no longer sexually alluring to them for any number of reasons, off their cases about sex for awhile. Cialis takes the tack of the woman being affectionate, attentive, and available. Nice sentiments but given today’s housing prices and cost of living two working parents are probably too dead tired after work to have sex.
6-Today’s 50% plus divorce rate and about the same percentage of married men and women admitting to adultery suggests romantic love as the predicate for marriage often doesn‘t outlive today‘s increased longevity for men and women. In fact, romantic love is a very late comer to the reasons people marry. In that connection I wrote in a recent private letter to the publisher of AARP Magazine, “…I suggest a change in editorial emphasis to downplay senior romance which is really a ridiculous notion in today‘s world of a 50%+ divorce rate, and about half of married women admitting being unfaithful…AARP should run articles showing how men can create fulfilling lives alone.”
7- Most cultures down through the ages recognized how inherently difficult marriage is by making divorce very difficult to obtain. Perhaps the best evidence of this are marriage jokes which usually comprise the largest section in joke anthologies. Some samples: (Rita Rudner)-Asked mother how she and dad stayed married 50 years. She said, “Just close your eyes and pretend it’s not happening.” (Groucho Marx)-Marriage is a wonderful institution, but who wants to live in a institution; (Jean Kerr)-Marrying a man is like buying something you’ve been admiring for a long time in a shop window. You may love it when you get it home, but it always doesn’t go with everything else in the house. (Milton Berle)-Told my wife black underwear turns me on, so she didn’t wash my shorts for a month; (Zsa Zsa Gabor)-A man in love is incomplete until he marries. Then he’s finished. (Joan Collins upon shedding husband #5 or 6) What I need is a wife! (Sir James Goldsmith)-The trouble with marrying your mistress is you create a job vacancy.
(Anonymous) Marriage is the high sea for which no compass has yet been in


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