From: EXECSEC
Sent: Monday, November 27, 2000 9:55 AM
To: Dockets, FDA
Subject: FW: Lotronex



-----Original Message-----
From: Emeran Mayer [mailto:emayer@ucla.edu] 
Sent: Monday, November 27, 2000 11:33 AM
To: EXECSEC
Subject: RE: Lotronex


November 24, 2000



Jane Henney, MD
Commissioner, Food and Drug Administration
5600 Fishers Lane
Rockville, MD 20857

RE:  FDA Advisory Meeting:   Lotronex: Assessment of Risk vs. Benefit;
Nov. 13, 2000


Dear Dr. Henney:

This letter is written in follow-up to the above meeting which I attended
on behalf of Glaxo Wellcome (GW).  As I indicated in my presentation, I did
not accept any honorarium or travel reimbursement from GW for my
attendance.  My sole motivation to attend the meeting was my desire to
prevent a premature ban of the first effective medical treatment for one of
the most common chronic medical conditions, i.e. IBS.   Having spent the
better part of my career in identifying a neurobiological basis for IBS,
changing the perception of the disorder from a "disorder of neurotic,
middle-aged housewives" to a medically treatable visceral pain disorder,
and convincing the pharmaceutical industry that it is possible to develop
effective medications for this disorder,  I have a vested interest in
preventing a turning back of the clock to point zero in IBS medical
treatment.  

I would like to reemphasize the key points of my presentation:

 Two thirds of women with a diagnosis of IBS suffer from chronic abdominal
pain at least three months out of the year, and 40% consider this pain
intolerable without some form of relief.
 The impact of moderate to severe IBS on quality of life is comparable to
some of the most debilitating chronic medical and psychiatric conditions.
 Despite this evidence, two independent groups came to the same sobering
conclusion from an extensive review of the literature: except for the
repeated demonstrations of superiority of Lotronex over placebo, there is
no scientific evidence that ANY drug currently available drug in the US is
superior to placebo treatment.   This has several devastating consequences:
 The most prevalent medical treatments are archaic (i.e. not better than
traditional folk medicines), associated with frequent side effects, and
many women who are refractory to such treatments, end up with unnecessary
hospitalizations, diagnostic procedures and surgeries (cholecystecomies,
hysterectomies, surgery for endometriosis or adhesions).
 The reason for this surprising situation is largely a result of the
unwillingness of the pharmaceutical industry for many years to invest in a
risky drug development program for a disease which not too long ago was not
considered amenable to rational drug therapy.  With the demonstration of
plausible biological models for symptom generation in IBS, the research
community has only recently been able to change this situation, and several
major companies, including GW have embarked on developing novel medical
treatments.
 With the advent of Lotronex, this situation has changed dramatically:
the effectiveness of the drug demonstrated to funding agencies and to the
pharmaceutical industry that this disorder can be treated medically, and
that it no longer should be considered a psychosomatic disorder.
 A banning of this pioneering treatment will send a signal to the industry
that despite an effectiveness of this drug comparable to some of the most
effective medical treatments for pain, depression, and heartburn, the FDA
has a much lower threshold for tolerating side effects in this group of
chronic pain conditions than any other medical conditions.  This signal
could result in all major companies currently involved in drug development
in this field to discontinue their efforts, and let the field return to the
realm of folk medicine once again.  On the other side, a success of
Lotronex will stimulate GW's competitors to invest an even greater effort
in developing even better medical therapies. It is ironic that so called
consumer advocates want to have a medication withdrawn from the market,
which will return hundred of thousands of affected women to their miserable
lifes of chronic pain and discomfort.

I want to emphasize that as a responsible physician, I am very much
concerned about the troubling side effects some patients have experienced
while being on Lotronex treatment.  However, none of the
gastroenterologists within our program, or those within the UCLA Digestive
Disease Division has seen a single case of ischemic colitis, or severe
constipation develop in any of our patients on Lotronex, despite the fact
that we have participated in all clinical trials with Lotronex for the past
3 years, and despite having prescribed the medication to a large number of
patients.  I am therefore firmly convinced that the reported complications
with the drug are largely related to physician errors in indication,
instruction to the patients, and lack of sensitivity to possible warning
signs (symptom exacerbation, or development of constipation while on drug
treatment).  It would be tragic if a highly effective medication would be
banned based not on a problem with the medication, but on a lack of
knowledge of the prescribers of this medication. 

Based on the above reasons, I urge you not to take Lotronex off the market
but rather to work with GW and academic throught leaders on IBS across the
country to develop better education of patients and prescribers, and
optimized dosing schedules  to further reduce the side effects of this drug.

Thank you for your consideration.

Kind regards, 


Emeran A. Mayer, M.D.
Professor of Medicine and Physiology
Head, CURE Neuroenteric Disease Program
Associated Director, CURE:  Digestive Diseases Research Center
UCLA Division of Digestive Diseases




At 08:27 AM 11/27/2000 -0500, you wrote:
>Emeran Mayer:
>
>Due to computer security concerns, we do not open attachments from the
>public.  Please resend your message without an attachment.
>
>FDA
>Executive Secretariat
>
>-----Original Message-----
>From: Emeran Mayer [mailto:emayer@ucla.edu]
>Sent: Friday, November 24, 2000 6:52 PM
>To: JHENNEY@OC.FDA.GOV
>Subject: Lotronex
>
>
>Please see attached letter.
>






Emeran A. Mayer, M.D.
Professor of Medicine, Biobehavioral Sciences & Physiology
UCLA Mind Body CRC & CURE Neuroenteric Disease Program
UCLA Division of Digestive Diseases
GLA VA HS. Bldg. 115/CURE
11301 Wilshire Blvd., Los Angeles, CA 90073
Tel.  310 312-9276
FAX   310 794-2864
http://www.med.ucla.edu/Cure
http://www.med.ucla.edu/ndp/