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Lotronex, the first product for the treatment of irritable
bowel syndrome (IBS), was voluntarily withdrawn by Glaxo
Wellcome on November 28 2000. Reports of adverse events
initially led the FDA to require the inclusion of a patient
Medication Guide with each prescription.
However, the deaths of five women, that may have been linked
to Lotronex use, prompted the recent withdrawal. Another
treatment for IBS, Novartis' Zelmac, is expected to be launched
during the first half of 2001.
Voluntary withdrawal
Glaxo Wellcome voluntarily withdrew Lotronex, its drug for
the treatment of irritable bowel syndrome, from the US market
on November 28 2000, at the request of the US Food and Drug
Administration (FDA).
Glaxo has also stated that it will not market Lotronex in
countries where it has already received approval (Mexico,
Argentina, Brazil and South Korea) and that it will relinquish
licenses granted and withdraw all regulatory submissions.
In short, Glaxo has abandoned plans to market Lotronex worldwide.
A brief history
The cause of IBS is unknown, however it is a common condition
and is thought to affect about 20% of the US population
with twice as many women as men suffering. Symptoms include
abdominal pain, irregular pattern of defaecation, and bloating
or abdominal distention.
Traditional treatments include anticholinergics, barbiturates,
antidepressants, benzodiazepines, fibre supplements and
opioids - but none are effective for relieving
overall symptoms.
Lotronex, a 5-HT3 receptor
antagonist, was the first product in a new class of
drugs for the treatment of IBS. Lotronex (alosetron) was
indicated for the treatment of IBS in female patients who
had diarrhoea as the predominant symptom (as opposed to
constipation) - it was not indicated for use in men.
US launch
Glaxo received its first approval for Lotronex in the USA
in February 2000 and launched the product in March. It was
the first treatment for IBS to reach the global market and
analysts were predicting potential blockbuster status.
Glaxo's US strategy was to raise awareness of IBS among
female consumers, through an intense direct-to-consumer
(DTC) advertising campaign. Since March, Lotronex has amassed
sales of $44 million to the end of September 2000.
Lotronex Sales March to September 2000
Source: MIDAS
Warning signs
In early June 2000, the FDA called a meeting, to be held
at the end of the month, to discuss revisions to Lotronex's
labeling because of reports of adverse events involving
ischaemic colitis and severe constipation. At this time,
Glaxo made a decision to delay its DTC campaign until the
review was complete.
Incorrect prescribing was one of the FDA's concerns, since
some of the Lotronex adverse events appeared to have been
caused by physicians prescribing the drug to women who should
not have taken it in the first place. As a result, Glaxo
planned a campaign to educate doctors to make sure they
were correctly using Lotronex and to provide patient leaflets
explaining side effects and outlining who should avoid the
drug.
Labeling change
On August 24 2000 the FDA announced that Lotronex was to
be the first product required to have a patient Medication
Guide provided with each prescription - informing patients
of the risk of constipation and ischaemic colitis. This
decision was reached to ensure that patients "will understand
the rare but serious risks of Lotronex and how they can
recognize those risks and take early action to prevent serious
harm".
Also in August, the US consumer group, Public Citizen, petitioned
the FDA to withdraw Lotronex, but the FDA stated that it
believed the benefits of Lotronex outweighed the risks.
Withdrawal
At the end of October however, the FDA began investigating
the deaths of five women, which may have been linked to
Lotronex use. At the same time, Glaxo announced that it
planned to go ahead with the launch of Lotronex in the UK
market. The UK launch did not take place and Glaxo's voluntary
withdrawal means the end to further Lotronex launches.
Future of IBS treatment
The withdrawal of Lotronex means that there continues to
be an unmet need in the treatment of IBS. Other products
are in development, but the next product most likely to
reach the market will be Zelmac (tegaserod) from Novartis.
Novartis applied for approval of Zelmac in the USA and European
Union in early 2000. Zelmac is a partial agonist of 5-HT4
receptors and is indicated for the treatment of constipation-predominant
IBS in women.
In August, the FDA deemed the product approvable, but requested
additional data. Nevertheless, Novartis still expects to
launch Zelmac in the USA during the first half of 2001.
In October 2000, Novartis entered into a co-marketing agreement
for Zelmac with Bristol-Myers Squibb, for all major markets
except Japan.
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