Fw: Women With Irritable Bowel Syndrome ~ Alosetron

[Guest guest]

From: " ilena rose " <ilena@...>

Sent: Saturday, July 28, 2001 10:57 PM

Subject: Women With Irritable Bowel Syndrome ~ Alosetron

> ~~~ thank you Nurse Boone ... so many of our women suffer from IBS ~~~

>>

http://internalmedicine.medscape.com/reuters/prof/2001/07/07.25/20010724clin

007.

> html

>

> Alosetron Helpful in Subset of Women With Irritable Bowel Syndrome

> ------------------------------------------------------------------------

>

> WESTPORT, CT (Reuters Health) Jul 24 - Alosetron hydrochloride is

effective

> in treating irritable bowel syndrome (IBS) in certain female patients,

> researchers report in the July 23rd issue of the Archives of Internal

> Medicine.

>

> Dr. M. Mangel, of Glaxo Wellcome Inc., Research Triangle Park, North

> Carolina, and colleagues randomized 626 women with IBS in a double-blind

> fashion to 1 mg of alosetron or placebo twice daily for 12 weeks. The

> patients were then observed for a further 4 weeks.

>

> Altogether, 71% of patients were classified as having diarrhea-predominant

> IBS and 43% of alosetron-treated patients in this group reported at least

2

> weeks per month with " adequate " pain relief for all 3 months. This was

true

> of only 26% of such patients given placebo.

>

> The researchers report that there were no significant differences in

> response to alosetron between diarrhea-predominant patients and those who

> alternated between diarrhea and constipation; " however, the magnitude of

> efficacy was numerically greater in diarrhea-predominant patients. "

>

> In the diarrhea-predominant group, alosetron treatment " significantly

> decreased urgency and stool frequency and caused firmer stools within 1

> week of starting treatment. " However, no significant improvement was seen

> in the first 4 weeks in percentage of days with a sense of incomplete

> evacuation or bloating. Constipation was the most common side effect.

>

> The researchers conclude that alosetron " is effective in relieving pain

and

> some bowel-related symptoms in diarrhea-predominant female patients with

> IBS. "

>

> [Alosetron was withdrawn from the US market in 2000. See related Medscape

> newsbeat.] Arch Intern Med 2001;161:1733-1740.

>

> There are many related articles here:

>

http://www.medscape.com/Medscape/features/newsbeat/2000/0800/Alosetron.html

>

> http://www.medscape.com/reuters/prof/2001/05/05.18/20010517rglt008.html

> Lancet Questions FDA Integrity, Claiming Drug Industry Influence

> ------------------------------------------------------------------------

>

> LONDON (Reuters Health) May 17 - Patients taking a controversial new drug

> for irritable bowel syndrome may have died because the US Food and Drug

> Administration has become the " servant of the drug industry, " the editor

of

> The Lancet claimed on Thursday.

>

> In a devastating editorial, Horton said that although

> GlaxoKline voluntarily withdrew alosetron (Lotronex) from the US

> market last November after the deaths of five patients, senior FDA

> officials were now seeking to reintroduce it.

>

> " This story reveals not only dangerous failings in a single drug's

approval

> and review process but also the extent to which the FDA, its Center for

> Drug Evaluation and Research (CDER) in particular, has become the servant

> of industry, " Horton said.

>

> The 2-page editorial, entitled " Lotronex and the FDA: a fatal erosion of

> integrity, " accuses the FDA of receiving hundreds of millions of dollars

in

> funding from industry.

>

> It claims the views of FDA scientists who raised safety questions about

the

> drug were dismissed by FDA officials and that the scientists were excluded

> from further discussion about the drug's future.

>

> The editorial also alleges that negotiations between the FDA and

> GlaxoKline on Lotronex's future involved a " two-track process, one

> official and transparent, one unofficial and covert. "

>

> Lotronex, a new 5-HT antagonist class of drug for irritable bowel

syndrome,

> was licensed by the FDA in February 2000, but was never approved by the

> European Medicines Evaluation Agency.

>

> The company withdrew the product in the US on November 28 after 49 cases

of

> ischaemic colitis and 21 cases of severe constipation, including instances

> of obstructed and ruptured bowel, were reported. In addition to 5 deaths,

> 34 patients required admission to hospital and 10 needed surgery.

>

> Horton writes that as early as July, it was known that seven patients had

> developed serious complications. The clinical data confirmed " substantial

> and potentially life-threatening risks " but instead of withdrawing

> Lotronex, the FDA issued a medication guide. " This decision was to prove

> fatal. "

>

> The editorialist also points out that FDA scientists knew that the

> medication guide, which advised patients to stop taking Lotronex if they

> felt " increasing abdominal discomfort " was impractical since abdominal

pain

> is also a " cardinal symptom of an irritable bowel. "

>

> " FDA scientists argued that it was unreasonable to expect either patients

> or their physicians to judge pain as an early warning of possibly fatal

> ischaemic colitis, " he continues. " This view was dismissed by FDA

> officials.

>

> " The scientists who raised these issues felt intimidated by senior

> colleagues and were excluded from further discussions about Lotronex's

> future. "

>

> In a memorandum dated November 16, FDA scientists said: " Early warning of

> the dire side effects of this drug is clearly not feasible " and added a

> " risk management plan cannot be successful. "

>

> However, this conclusion was blurred by the time of the key November 28

> meeting between GlaxoKline and FDA officials. Rather than reject the

> company's risk management proposal and withdraw Lotronex, the FDA offered

> several conciliatory options including voluntary withdrawal pending

further

> discussion.

>

> Horton claims " many within the FDA leadership now want to bring Lotronex

> back. An advisory committee meeting set up to do so is being planned for

> June or July. "

>

> Horton told Reuters Health he became interested in Lotronex because The

> Lancet published some of the trial data that led to the FDA approving the

> drug. " As the year went on, we noticed that there were increasing reports

> of adverse events. "

>

> " Then as I got more intrigued about what was happening, it opened up into

> an issue of how science is dealt with by the FDA and how, because of

> industry funding, it has fatally compromised its independence. "

>

> " The scientists within the FDA who analyse and interpret adverse drug

> reactions have been largely ignored after the drug was approved and

> marketed. That is where there has been a terrible failure in evaluating

the

> safety of this drug. "

>

> " The FDA is not only compromised because it receives so much funding from

> industry, but because it comes under incredible Congressional pressure to

> be favourable to industry. That has led to deaths. "

>

> Horton pointed out that irritable bowel syndrome may be an extremely

> unpleasant condition, but is not life-threatening. To approve a drug that

> can lead to ruptured bowel and death is at odds with the normal balance

> between risk and benefit, he said.

>

> " This is a drug whose application was approved for full unrestricted

> marketing within 7 months. That is insufficient to gather safety data.

> Pushing through an application so quickly is irresponsible. "

>

> Horton said that GlaxoKline " has failed to gather sufficient evidence

> to justify the safety of this product. " He added that the company had

> applied pressure through private communication to senior FDA officials.

> " Instead of an accountable review process, one has a covert, unofficial

> process. "

>

> This is not Horton's first attack on the drug industry. In recent

> editorials, he has criticised the " tightening grip of big pharma " over

what

> researchers can publish in medical journals.

>

> In his current Lancet editorial Horton recommends that:

>

>

> * Lotronex should be reclassified as an investigational new drug,

> limiting its use to experimental settings only.

>

> * Covert private communications between FDA officials and industry

> must stop.

>

> * Drug approvals and safety reviews should take place through

> accountable procedures.

>

> * Greater weight should be given to the epidemiological advice

> provided to advisory committees.

>

> * There should be an independent congressional audit of the FDA's

> drug approval processes.

>

> * Pharmacovigilance should be removed from CDER's control because

> safety cannot be overseen by a center that receives industry funding.

>

> * FDA should welcome, not censure, differences of opinion within the

> organization.

>

> * The FDA's new commissioner should be an epidemiologically trained

> physician experienced in conducting clinical trials and independent of

> industry.

>

>

> GlaxoKline spokesman Sutton told Reuters: " We regard the

> editorial as misleading. There have been discussions between FDA and

> GlaxoKline officials. These meetings have all been conducted

according

> to usual regulatory and industry practices. Both the FDA and ourselves are

> trying to find a resolution that will benefit and protect patients. "

>

> Sutton added that the timing of any advisory committee meetings was a

> matter for the FDA.

>

> An FDA spokesperson said the agency is still formulating its response to

> the editorial.

>

> GlaxoKline chief executive Jean-Pierre Garnier said in April he

> believed the odds were low that Lotronex would be relaunched because of

the

> difficulty of predicting which patients might be at risk of severe side

> effects.

>

> However, industry analysts who have met R & D head Tachi Yamada more

recently

> told Reuters that the company now appeared to be more optimistic about a

> Lotronex relaunch.

>

> Lancet 2001;357(9268):000-000 http://www.thelancet.com [registration

required]

>

>

>