Zelnorm

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Zelnorm

• John J. Driscoll
• Brown Crouppen, P.C.
• 720 Olive St., Ste. 1800
• St. Louis, MO 63101
• 314-421-0216
• jdriscoll_at_brownandcrouppen.com

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How much revenue was produced by Zelnorm?

• In 2006, global sales grew 34 to 561 million,
  488 million came from the United States market.

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Why were Zelnorm sales suspended?

• An analysis of 29 clinical trials showed that of
  the 11,614 patients who took Zelnorm, 13 had
  cardiovascular events such as angina, heart
  attacks or stroke, at a rate of 0.11.
• For placebo patients, the rate was 0.01.
• Norvartis claims that the patients who had
  problems had underlying cardiovascular risk
  factors or disease.

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What is IBS?

• IBS is an intestinal disorder characterized by
  abdominal pain or discomfort, cramping or
  bloating, and diarrhea or constipation.
• Many people with IBS have alternating periods of
  constipation and diarrhea but often one is more
  common than the other.
• IBS is a long-term but manageable condition. It
  does not become worse over time and it does not
  lead to more serious diseases.

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Who is affected by IBS?

• IBS affects about 10 -15 of people in North
  America. UP to 20 of people have symptoms of
  IBS such as abdominal pain and altered bowel
  habits, although less than half of them see a
  doctor for their symptoms.
• IBS is twice as common in women than men.
• In the US it is estimated that 14-24 of women
  and 5-19 of men are affected by IBS.
• IBS is also common in India, Japan and China.
• IBS is less likely to develop for the first time
  in people over the age of 50.

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What increases your risk?

• IBS tends to be more common in people with

• People under the age of 35. One half of the
  people with IBS develop symptoms before the age
  of 35. 40 develop symptoms between the ages of
  35-50.
• Women. IBS is 2-3 times more common in women
  than in men.
• People with panic disorder or other psychological
  conditions.
• Individuals with a family history of IBS
• Individuals with a history of physical or sexual
  abuse or other psychological trauma.
• Individuals with chronic fatigue syndrome.
• Individuals with Fibromyalgia.
• Individuals with Temporomandibular disorder.

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Women and Heart Disease

• According to the AHA, heart disease is the 1
  cause of death of women. The number of women who
  die every year exceeds the number who die as a
  result of the next seven causes of death
  combined.
• Women are 15 more likely than men to die of a
  heart attack (Myocardial Infarction).
• Women are twice as likely as men to have a second
  Myocardial Infarction within the first 6 years
  following the first.

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Zelnorm Label History

• There have been four label changes approved by
  the FDA

• First Label approved 7/24/2002
• First Label change approved 4/15/2004
• Second Label change approved 4/21/2004
• Third Label change approved 8/21/2004
• Fourth Label change approved 3/1/2007

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Zelnorm Approval HistoryNDA 021200
http//www.accessdata.fda.gov/scripts/cder/drugsat
fda/index.cfm?fuseactionSearch.Label_ApprovalHist
ory.com
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First Label approved 7/24/2002

• Original PRECAUTIONS section read as follows

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First Label approved 7/24/2002
Original INFORMATION FOR PATIENTS section read
as follows
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First Label approved 7/24/2002
Original ADVERSE RECATIONS section included the
following adverse reactions as indicated with
Phase III clinical trials (but not limited to)
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First Label change approved 4/15/2004
DEAR DR. LETTER ISSUED 4/26/2004 FROM Novartis
Pharmaceuticals Corporation. All information
below can be found on the first label change
SUBMITTED ON 3/3/2004 approved by the FDA on
4/15/2004 Novartis informs health professionals
about the rare but serious consequences of
diarrhea
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First Label change approved 4/15/2004
Novartis revises the Zelnorm-Induced Diarrhea
section in ADVERSE REACTIONS by adding the
following sentence (see underlined text)
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First Label change approved 4/15/2004

• The PRECAUTION section is revised as follows to
  include information about Ischemic Colitis

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First Label change approved 4/15/2004
The INFORMATION FOR PATIENTS section now reflects
the following sentence about persistent abdominal
pain
The POST MARKETING EXPERIENCE section is changed
as follows (see underlined text)
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Second Label change approved 4/21/2004
FORMULATION REVISION AND LABEL CHANGES SUBMITTED
BY NOVARTIS ON 12/22/2003 APPROVED BY FDA ON
4/21/2004.
WARNING section is removed from the
label. PRECAUTIONS section now reads as follows
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Second Label change approved 4/21/2004
INFORMATION FOR PATIENTS section now reads as
follows
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Third Label change approved 8/21/2004
THE FOLLOWING WAS SUBMITTED ON 10/20/2003 AND WAS
APPROVED BY THE FDA ON 8/21/2004
The following was changed in the CLINICAL STUDIES
section to distinguish the difference in efficacy
in regards to gender For men, there were no
significant differences between placebo and
Zelnorm response rates. CLINICAL STUDIES section
was also changed to reflect the effectiveness of
Zelnorm for patients with Chronic Idiopathic
Constipation For women under 65, Zelnorm was
statistically significant in reducing the
symptoms associated with Chronic Idiopathic
Constipation. For women over age 65, there were
no significant treatment effects for Zelnorm over
placebo.
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Third Label change approved 8/21/2004
INDICATIONS AND USAGE section now reflects the
indication for Chronic Idiopathic Constipation
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Third Label change approved 8/21/2004
GERIATRIC section now reads as follows reflecting
the data gathered on patients over age 65
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Fourth Label change approved 3/1/2007
THE FOLLOWING WAS SUBMITTED BY NOVARTIS ON
8/31/2006 AND WAS APPROVED BY THE FDA ON 3/1/2007.
POST MARKET EXPERIENCES now reads as follows with
the addition of evelvated ALT, AST and bilirubin,
hepatitis and alopecia
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NOVARTIS

• Novartis AG is engaged in the research,
  development, manufacture and marketing of
  medicines.
• The company is divided into four different
  operating divisions Pharmaceuticals, Vaccines
  and Diagnostics, Sandoz, and Consumer Health.

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John J. DriscollBrown Crouppen, P.C.720 Olive
St., Ste. 1800St. Louis, MO 63101314-421-0216j
driscoll_at_brownandcrouppen.com