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/