More to life

TREAT HEARTBURN AND BEYOND TREAT HEARTBURN AND BEYOND

‘‘ There’s more to my life than GERD

0 Winning Seasons 2 5 County Championships 1 ACIPHEX tablet daily

GERD=gastroesophageal reflux disease

PLEASE SEE INDICATIONS AND IMPORTANT SAFETY INFORMATION ON PAGE 5.

“

Prescribe ACIPHEX to relieve heartburn & other symptoms of nonerosive GERD— regurgitation, belching & early satiety, because…

RECENT research supports an association between BMI and GERD symptoms1-4

received ACIPHEX 20 mg once a day or placebo for 4 weeks

• Analysis

was performed in the ITT population (ACIPHEX, n=126; placebo, n=126)

• Eats meals late • BMI=32, struggles with weight

• Was embarrassed by belching

overweight or obese (BMI≥25) is a risk factor for GERD symptoms1

• Being • The

risk of reflux symptoms doubles for patients who are overweight (BMI 25 to 30)2

• The

risk triples for patients who are obese (BMI>30 to 35)2

ACIPHEX significantly reduced severity of regurgitation, belching and early satiety at 4 weeks*†5

2X

BASELINE WEEK 4

Regurgitation

GREATER FREQUENCY

of heartburn and regurgitation4

• Patients taking placebo had a

reduction in regurgitation from 1.05 at baseline to 0.72 at week 4; a reduction in belching from 1.47 at baseline to 1.06 at week 4; and a reduction in early satiety from 1.28 at baseline to 0.91 at week 4. All P values were <0.0015

‡

Belching ‡

Early Satiety ‡

P<0.001 vs baseline.

‡

0 None

‘‘ There’s more to my life than GERD

1 Mild

AVERAGE SYMPTOM SCORES

2 Moderate

*Symptom severity scores were recorded daily (0=none; 1=mild; 2=moderate; 3=severe; 4=very severe). † Compared with placebo, at week 4 ACIPHEX significantly reduced severity of regurgitation (P=0.006), belching (P=0.007) and early satiety (P=0.04).

ACIPHEX significantly reduced nighttime and daytime heartburn severity§k5 Moderate 2

0 Winning Seasons 2 5 County Championships 1 ACIPHEX tablet daily

AVERAGE HEARTBURN SYMPTOM SCORES

• Woke with heartburn and regurgitation

BMI ≥ 30

“

• Takes medicine to control his diabetes

TREAT HEARTBURN AND BEYOND

• Patients

• Coaches soccer 3 nights a week

GERD SYMPTOMS

FRANK’S CHALLENGE:

In a combined analysis of 2 placebo-controlled studies (N=261) in nonerosive GERD patients with moderate to very severe heartburn5,6 —

Hypothetical representation of a patient with symptomatic nonerosive GERD.

1.92

DAY NIGHT

1.73 Mild 1

0.78¶ 0.68¶

None 0

• Patients taking placebo had a

reduction in nighttime heartburn from 1.82 at baseline to 1.12 at week 4; and a reduction in daytime heartburn from 2.01 at baseline to 1.33 at week 4.

All P values were <0.0015

P<0.001 vs baseline.

¶

Baseline

AVERAGE SYMPTOM SCORES

Week 4

Symptom severity scores were recorded daily (0=none; 1=mild; 2=moderate; 3=severe; 4=very severe).

Compared with placebo, at week 4 ACIPHEX significantly reduced severity of nighttime heartburn (P=0.006) and daytime heartburn (P<0.001).

§ k

78%

of patients in these studies were overweight or obese (BMI≥25); however, BMI was not an enrollment criteria

PLEASE SEE INDICATIONS AND IMPORTANT SAFETY INFORMATION ON PAGE 5.

JANET’S CHALLENGE:

• Recently quit smoking

With ACIPHEX, patients were without relapse of nighttime heartburn severity at 1 year*6-8

• BMI=28, battles with her weight • Making dietary changes

• Suffered bouts of nighttime and daytime heartburn

ACIPHEX maintained endoscopic healing at 1 year§6-8 ACIPHEX 20 mg

ACIPHEX 20 mg

98%

†

Study 1

• Takes medicine to control high blood pressure • Previously healed erosive GERD (H pylori negative)

TREAT HEARTBURN AND BEYOND

91% 20

40

60

80

K

86%

K

Study 2 † ‡

0

90%

Study 1

‡

Study 2

HEALING & SAFETY INFORMATION

• Heads local volunteer organization

ACIPHEX delivered symptom relief and maintained healing

Ps0.001 vs placebo.

0.001<P<0.05 vs placebo.

P<0.001 vs placebo.

||

100

0

% OF PATIENTS WITHOUT RELAPSE OF HEARTBURN SEVERITY

* Two US multicenter, double-blind, randomized, parallel-group studies of patients with previously healed erosive or ulcerative GERD treated for 1 year (N=209; N=285).

20

40

60

80

% OF PATIENTS WHO REMAINED HEALED

100

Two US multicenter, double-blind, randomized, parallel-group studies of patients with previously healed erosive or ulcerative GERD treated for 1 year (N=209, N=285).

§

• Of

• 97%†

and 94%† of patients were without relapse of daytime heartburn severity at 1 year in study 1 and study 2, respectively

patients taking placebo, 29% remained healed at 1 year in both studies§6-8

CONTROLLED STUDIES DO NOT EXTEND BEYOND 12 MONTHS.

• Of

patients taking placebo, 66% to 74% were without relapse of nighttime heartburn severity and 69% to 74% were without relapse of daytime heartburn severity at 1 year*6-8 CONTROLLED STUDIES DO NOT EXTEND BEYOND 12 MONTHS.

‘‘ There’s more to my life than GERD 30 Dedicated Weekends 7 Homes Built 1 ACIPHEX tablet daily

Hypothetical representation of a patient with previously healed erosive GERD.

“

SYMPTOM RELIEF

IN EROSIVE GERD…

Indications ACIPHEX 20 mg is indicated for: treatment of daytime and nighttime heartburn and other symptoms of GERD; short-term, up to 4 weeks, treatment in the healing and symptomatic relief of duodenal ulcers; short-term, 4 to 8 weeks, treatment in the healing and symptomatic relief of erosive GERD; and maintenance of healing and reduction in relapse rates of heartburn symptoms of erosive GERD (controlled maintenance studies do not extend beyond 12 months).

Important Safety Information In clinical trials the most common side effect assessed as possibly or probably related to ACIPHEX with a frequency greater than placebo was headache (2.4% vs 1.6% for placebo).

Symptomatic response to therapy does not preclude the presence of gastric malignancy. ACIPHEX is contraindicated in patients with known hypersensitivity to rabeprazole, substituted benzimidazoles, or to any component of the formulation.

Patients treated with a proton pump inhibitor and warfarin concomitantly may need to be monitored for increases in INR and prothrombin time.

POTENT ACID SUPPRESSION

ACIPHEX—Potent Acid Suppression

ACIPHEX is not solely metabolized by the cytochrome P450 system6,9

Potent gastric acid suppression*5,6

ACIPHEX Metabolism

ACIPHEX 20 mg placebo

Day 1

44%

8%

†

CYP3A CYP2C19

60%

11%

rabeprazole thioether

†

rabeprazole sulphone †

0

20

40

60

80

% OF TIME GASTRIC pH>4 DURING 24 HOURS

P<0.001 vs placebo.

100

*A single-center, double-blind, placebo-controlled, randomized crossover study in healthy H pylori-negative male subjects (N=24). Analysis was performed in 23 evaluable subjects.

• ACIPHEX

desmethyl rabeprazole • Nonenzymatic

reduction is a primary route of metabolism for ACIPHEX

significantly maintained gastric pH>4 for 44% and 60% of the 24-hour period on day 1 and day 8,* respectively 5,6

THE CORRELATION OF THESE DATA TO CLINICAL EFFECT HAS NOT BEEN ESTABLISHED.

Esophageal pH≥4 on day 7‡5,6

ACIPHEX—convenient once-daily dosing for your GERD patients6 ACIPHEX 20 mg

95%

Day 7

actual size

(22.8 hours)

0

METABOLISM & DOSING

Day 8

NONENZYMATIC REDUCTION (systemic)

20

40

60

80

% OF TIME ESOPHAGEAL pHt4 DURING 24 HOURS

• •

Small tablet Can be taken with or without food

100

A single-center, double-blind, randomized, two-way crossover study of 20 and 40 mg rabeprazole in GERD patients (N=20). In the 20 mg arm, percentage of time esophageal pH<4 decreased from a baseline of 24.7% to 5.1% on day 7.

‡

• ACIPHEX

maintained esophageal pH≥4 for the majority of the day‡5,6

THE CORRELATION OF THESE PHARMACODYNAMIC DATA TO CLINICAL EFFECT HAS NOT BEEN ESTABLISHED.

PLEASE SEE INDICATIONS AND IMPORTANT SAFETY INFORMATION ON PAGE 5.

References: 1. El-Serag HB, Graham DY, Satia JA, Rabeneck L. Obesity is an independent risk factor for GERD symptoms and erosive esophagitis. Am J Gastroenterol. 2005;100:1243-1250. 2. Nilsson M, Johnsen R, Ye W, Hveem K, Lagergren J. Obesity and estrogen as risk factors for gastroesophageal reflux symptoms. JAMA. 2003;290:66-72. 3. Hampel H, Abraham NS, El-Serag HB. Meta-analysis: obesity and the risk for gastroesophageal reflux disease and its complications.

Ann Intern Med. 2005;143:199-211. 4. Murray L, Johnston B, Lane A, et al. Relationship between body mass and gastrooesophageal reflux symptoms: The Bristol Helicobacter Project. Int J Epidemiol. 2003;32:645-650. 5. Data on file, Eisai Inc. 6. ACIPHEX full prescribing information. 7. Caos A, Moskovitz M, Dayal Y, Perdomo C, Niecestro R, Barth J, and the Rabeprazole Study Group. Rabeprazole for the prevention of pathologic and symptomatic relapse of erosive or ulcerative gastroesophageal reflux disease. Am J Gastroenterol. 2000;95:3081-3088. 8. Birbara C, Breiter J, Perdomo C, Hahne W, and the Rabeprazole Study Group. Rabeprazole for the prevention of recurrent erosive or ulcerative gastro-oesophageal reflux disease. Eur J Gastroenterol Hepatol. 2000;12:889-897. 9. Yasuda S, Ohnishi A, Ogawa T, et al. Pharmacokinetic properties of E3810, a new proton pump inhibitor, in healthy male volunteers. Int J Clin Pharmacol Ther. 1994;32:466-473.

7

Prescribe ACIPHEX to relieve heartburn & other symptoms of nonerosive GERD— regurgitation, belching & early satiety, because…

TREAT HEARTBURN AND BEYOND

‘‘ There’s more to my life than GERD

“

TREAT HEARTBURN AND BEYOND

Prescribe ACIPHEX 20 mg once daily

PLEASE SEE INDICATIONS AND IMPORTANT SAFETY INFORMATION ON PAGE 5.

PLEASE SEE FULL PRESCRIBING INFORMATION. FOR SALES REPRESENTATIVE USE ONLY. NOT TO BE LEFT WITH PHYSICIAN. FURNISH PHYSICIAN WITH FULL PRESCRIBING INFORMATION. Manufactured and Marketed by

Woodcliff Lake, NJ 07677

Marketed by

Raritan, NJ 08869-0602

ACIPHEX is a registered trademark of Eisai Co., Ltd. © 2007 Eisai Inc. and Ortho-McNeil, Inc. 01AX1509 Jun. 2007

In clinical trials, ACIPHEX helped relieve heartburn and beyond by treating associated symptoms in nonerosive GERD patients, including those who were overweight and obese LIFT FOR STUDY DESIGN.