Slide 1

Effect of Combination Therapy with PROSCAR™† (finasteride, MSD) and

Doxazosin on the Risk of Clinical Progression of BPH by

Total Baseline Prostate Volume

New Analysis from the Medical Therapy Of Prostatic Symptoms Trial (MTOPS)

†Trademark of Merck & Co., Inc., Whitehouse Station, NJ, USA

Slide 2

Ref 3, p 18,C1, ¶4,L1-5

Ref 3, p 17,C2, ¶3, L12-18 Ref 3, p 18,C1, ¶2,L1-3,13-16 Ref 4,p 2,Figure

BPH=benign prostatic hyperplasia

Adapted from Roehrborn CG Curr Opin Urol 2001;11:17–25; National Cancer Institute. NIH Publication No. 99-4303, 1999.

Alpha-blockers 5-Alpha-reductase inhibitors

Improve symptoms and increase urinary flow rate by relaxing prostatic and bladder-neck smooth muscle through sympathetic activity blockade

Improve symptoms, increase urinary flow rate, and prevent BPH outcomes by reducing prostate enlargement through hormonal mechanisms

Complementary Mechanism of Action to Provide Both Fast Symptom Relief and Sustained BPH Control

Slide 3

Study Design: Overview

Double-blind, placebo-controlled, multicenter, randomized clinical trial Average follow-up: 4.5 years

AUA=American Urological Association; Qmax=maximum urinary flow

Adapted from Bautista OM et al Control Clin Trials 2003;24:224–243.

RandomizedN=3047

Entry Criteria

• Men 50 years of age• AUA symptom score 8–

30• Qmax 4–15 ml/sec• Voided volume 125 ml

Doxazosin(n=756)

PROSCAR™†

(finasteride)(n=768)

PROSCAR +doxazosin

(n=786)

Placebo(n=737)

MTOPS (Medical Therapy Of Prostatic Symptoms)

†Trademark of Merck & Co., Inc., Whitehouse Station, NJ, USA

Ref 1, p 226, ¶2, L1-5, ¶3, L5-6; p 229, ¶1, L1-4, ¶2, L1-2; p 230, L1-4, ¶1, L1-3; p 231, Table 3; p 233, Table 4

Slide 4

Combination Therapy with PROSCAR™ plus Doxazosin Is Significantly More Effective than Either Drug Alone

Combination therapy with finasteride plus doxazosin is the most effective form of medical therapy for BPH

– 66% reduction in risk of BPH progression (p<0.001)

– 64% reduction in worsening symptoms (p<0.001)

– 81% reduction in risk of AUR (p<0.001)

– 67% reduction in need for invasive BPH therapy (p<0.001)

Long-term monotherapy and combination therapy were well tolerated and effective

AUR=acute urinary retention

Adapted from McConnell JD et al N Engl J Med 2003;349(25):2385–2396.

Ref 7, p 2394,C2, ¶2, L12-17;p 2388, C1,¶1, L10-11, C2,L1-2; p 2390,C1, ¶1, L4-9, C2, ¶1, L5-7;p 2391, C1,¶3, L10-14

Ref 7, p 2394,C2, ¶2, L12-15

MTOPS: Results

PROSCAR™ (finasteride) is a trademark of Merck & Co., Inc., Whitehouse Station, NJ, USA.

Slide 5

Ref 2, C1, Intro,Bullets 2,3Can Baseline Total Prostate

Volume Be Used to Identify Whom to Treat with

Combination Therapy?

MTOPS: A New Analysis

Slide 6

Statistical Methods in New Analysis

Intention-to-treat population

Evaluation of effects of baseline TPV on study measures

Results compared

– Across three clinically relevant baseline TPV subgroups

• <25 ml (small glands)

• 25–<40 ml (moderately sized glands)

• ≥40 ml (enlarged glands)

Ref 2, C1, Intro, Bullet 3, C2, Materials and Methods, Bullet 2

TPV=total prostate volumeAdapted from Kaplan SA et al. Presented at the annual meeting of the European Association of Urology, Istanbul, Turkey, March 16–19, 2005.

MTOPS: A New Analysis

Slide 7

TRUS=transrectal ultrasonography

Adapted from Kaplan SA et al. Presented at the annual meeting of the European Association of Urology, Istanbul, Turkey, March 16–19, 2005.

Demographics and Baseline Characteristics

Number of men 3047

Mean age 62.6 years

Mean AUA symptom score 16.9

Mean Qmax 10.5 ml/sec

Median prostate volume (TRUS) 31 ml

<25 ml 31%

25–<40 ml 38%

≥40 ml 31%

Ref 2,C1, ¶2, L7-9, C2, Materials & Methods, Bullet 1, L1

MTOPS: A New Analysis

No differences among groups

Slide 8

Relative Risk of BPH Progression by Baseline TPV Category

Ref 2, C3, Fig 1A

MTOPS: A New Analysis

CI=confidence interval

Adapted from Kaplan SA et al. Presented at the annual meeting of the European Association of Urology, Istanbul, Turkey, March 16–19, 2005.

00.20.40.60.81.01.200.20.40.60.81.01.21.41.6

Relative risk (95% CI) of BPH progression

≥40

25–<40

<25

Baseline TPV (ml)

Favorscombination therapy

Favorsdoxazosin

Favorscombination therapy

FavorsPROSCAR™

PROSCAR™ (finasteride) is a trademark of Merck & Co., Inc., Whitehouse Station, NJ, USA.

Slide 9

Relative Risk of Invasive Therapy by Baseline TPV Category

Ref 2, C3, Fig 1B

0123456700.511.522.53

Favorscombination therapy

Favorsdoxazosin

Favorscombination therapy

FavorsPROSCAR™

Relative risk (95% CI) of invasive therapy

MTOPS: A New Analysis

≥40

25–<40

<25

Baseline TPV (ml)

PROSCAR™ (finasteride) is a trademark of Merck & Co., Inc., Whitehouse Station, NJ, USA.

Adapted from Kaplan SA et al. Presented at the annual meeting of the European Association of Urology, Istanbul, Turkey, March 16–19, 2005.

Slide 10

Change in AUA Symptom Scores by Baseline TPV Category

Ref 2, C3, Fig 1C

–3–2–101

MTOPS: A New Analysis

–3–2–101

Favorscombination therapy

Favorsdoxazosin

Favorscombination therapy

FavorsPROSCAR™

Mean (95% CI) between-group difference in change from baseline at year 4

≥40

25–<40

<25

Baseline TPV (ml)

PROSCAR™ (finasteride) is a trademark of Merck & Co., Inc., Whitehouse Station, NJ, USA.

Adapted from Kaplan SA et al. Presented at the annual meeting of the European Association of Urology, Istanbul, Turkey, March 16–19, 2005.

Slide 11

Change in Maximum Urinary Flow Rate by Baseline TPV Category

Mean (95% CI) between-group difference in change from baseline at year 4 (ml/sec)

42–1 0 1 3 42–1 0 1 3

FavorsCombination Therapy

Favors doxazosin

FavorsCombination Therapy

FavorsPROSCAR™

MTOPS: A New Analysis

Ref 2, C3, Fig 1D≥40

25–<40

<25

Baseline TPV (ml)

PROSCAR™ (finasteride) is a trademark of Merck & Co., Inc., Whitehouse Station, NJ, USA.

Adapted from Kaplan SA et al. Presented at the annual meeting of the European Association of Urology, Istanbul, Turkey, March 16–19, 2005.

Slide 12

Conclusions

In patients with LUTS and TPV ≥25 ml– Combination therapy with PROSCAR™ plus

doxazosin led to superior overall management of BPH compared to either doxazosin or PROSCAR alone

In patients with LUTS and TPV < 25 ml– Combination therapy with PROSCAR plus

doxazosin led to a similar level of overall improvement versus doxazosin alone and a superior level of overall improvement relative to PROSCAR alone

MTOPS: A New Analysis

PROSCAR™ (finasteride) is a trademark of Merck & Co., Inc., Whitehouse Station, NJ, USA.

LUTS=lower urinary tract symptoms

Adapted from Kaplan SA et al. Presented at the annual meeting of the European Association of Urology, Istanbul, Turkey, March 16–19, 2005.

Ref 2, C3, Conclusions

Slide 13

MTOPS Results—Medical Therapy Decision Tree

MTOPS: A New Analysis

Adapted from Kaplan SA et al. Presented at the annual meeting of the European Association of Urology, Istanbul, Turkey, March 16–19, 2005.

LUTS patient withAUA symptom score ≥8

Determine TPV

TPV <25 ml TPV 25–<40 ml TPV ≥40 ml

Doxazosin Doxazosin + PROSCAR™

PROSCAR™ (finasteride) is a trademark of Merck & Co., Inc., Whitehouse Station, NJ, USA.

Ref 2, C3, Fig 2

Slide 14

References

Please refer to notes page.

Slide 15

Copyright © 2005 Merck & Co., Inc., Whitehouse Station, NJ, USA.

All rights reserved. 6-07 PSC 2004-W-14313-SS

VISIT US ON THE WORLD WIDE WEB AT http://www.merck.com

New Analysis from the Medical Therapy Of Prostatic Symptoms Trial (MTOPS)

Before prescribing, please consult the manufacturers’ prescribing information.

Merck does not recommend the use of any productin any different manner than as described

in the prescribing information.