# Presentation: 134952

## Summary of Efficacy

## Efficacy

- Erection
- Intercourse
- Timing/onset of action
- Couple/physician choice

*Clinical Considerations in ED*

- Efficacy Assessment

## Efficacy

- No standard physical measurement
- No accepted means of determining etiologies in most cases
- Duplex ultra sound, pharmacotesting and Nocturnal Penile Tumescense (NPT) are not used routinely
- The International Index of Erectile Function (IIEF*) and Brief Sexual Function Inventory (BSFI**) are validated clinical trial instruments

*Measurements of ED in Clinical Trials*

- 	*	Rosen et al. *Urology* 49:822-830, 1997.
- 	**	O’Leary et al. *Urology* 46:697-706, 1995.

- Efficacy Assessment

## Efficacy

- Determined after each dose administration (every attempt) from the home-use questionnaire
- Erection firm enough for intercourse based on patient response
- Erection firm enough for intercourse based on partner response
- Intercourse rates based on patient/partner responses

- Efficacy Assessment

*Uprima**® **Endpoints*

## Advantages of Home-Use Questionnairevs. Retrospective Questionnaire (e.g., IIEF)

- Direct assessment of efficacy at each dosing attempt
- Does not require patient to:
- Recall attempts after a 4-week period
- Create an estimate of average erectile function during that 4-week period

- Efficacy Assessment

- Efficacy

**Representative  ****ED Patient Population **

## Patient Population

- Heterosexual males, ages 18 – 70
- Partner consent
- Confirmed presence of ED (inability to attain and maintain erection firm enough for intercourse 50% of attempts 3 months prior to study)
- Physically able to obtain an erection documented by:
- Ability to attain and maintain an erection sufficient for intercourse on some occasion during 3 months prior to study i.e., nocturnal/morning erections or masturbation
- Nocturnal Penile Tumescence (NPT) testing with 55% or greater base rigidity for at least 10 minutes on at least 1 of 2 nights of NPT testing

*Phase III Studies (M96-470, M97-658, M98-941, M97-763)*

## Patient Population (cont.)

- No uncontrolled disease
- Clinically acceptable pre-study laboratory values, including normal testosterone and prolactin
- Diabetic patients: fasting glucose values <250 mg/dL, no episode of ketoacidosis within 3 months prior to study
- Hypertensive patients: Systolic Blood Pressure (SBP) <180 mm Hg and Diastolic Blood Pressure (DBP) <100 mm Hg
- Smokers: 1/2 pack per day
- Patients were excluded with a history of allergic reaction to morphine (or other opiates) or a history of pharmacotherapy for ED (within 3 months prior to study)

*Phase III Studies (M96-470, M97-658, M98-941, M97-763)*

- Patient Population

## Definition of “No Major Organic Component” 

- This term was used to exclude:
- Prostatectomy
- Spinal cord injury
- Parkinson’s disease
- Multiple sclerosis
- Penile prosthesis, penile deformity
- End-stage and unstable disease

- Patient Population

## Patient Demographics

**Age (yrs)****	****55.1****	****21 - 76****	****2379**
**Weight (lbs)****	****199.9****	****112 - 355****	****2376**
**Duration of Erectile Dysfunction****	****4.8 yrs****	****3 mo. - 47 yrs****	****1771**
**Race****	****	**
**   ****Caucasian****	**** 88.6%****	****	****2107**
**   ****Black****	****6.3%****	****	****  150**
**   ****Hispanic****	****3.6%****	****	****    85**
**   ****Asian/Pacific Islander****	****0.8%****	****	****    20**
**   ****Other****	****0.7%****	****	****    17**

**Range**

**N**

**Mean**

*Phase II/III Studies*

- Patient Population

## Representative ED Patient Population

- Subgroups with organic disease
- Baseline ED severity based on IIEF criteria
- RigiScan values compared with established norms
- Duration of ED

- Patient Population

## Major Subgroups

**Hypertension****	****31%**
**Diabetes****	****16%**
**Coronary Artery Disease****	****16%**
**Benign Prostatic Hyperplasia****	****16%**
**Alcohol Use****	****63%**
**Smoking****	****16%**

*Phase II/III Studies*

- Patient Population

## Baseline ED Severity Based on IIEF*

- Severe	39.3%
- Moderate	35.4%
- Mild	24.9%
- No ED	0.5%

*Phase III Studies **(M97-658, M97-763, M97-804, M98-941 and M98-876)*

- *	 <10	= Severe
- 		11-16	= Moderate
- 		17-25	= Mild
- 	 >25	= No ED

- Patient Population

## ED Population

**Medical Condition (%)****	****	****Hypertension****	****31%****	****25%****	****33% ****	****Coronary Artery Disease (CAD) ****	****16%****	****14%****	****  16%  ****	****Hyperlipidemia****	****16%****	****14%****	**** — ****	****	****Diabetes****	****16%****	****18%****	****9%**

- 1	Approval Package for Viagra® (Sildenafil Citrate). FDA.GOV/CDER/CONSUMERINFO/VIAGRA/VIAGRA/HTM. *Joint Clinical Review *p. 14. April 1999.
- 2	Johannes et al. *J. Urology* 163: 460-463, 2000.

**Uprima****®**** Studies**** **

**Viagra****®**** Studies****1**

**MMAS****2**

- Patient Population

## Comparison of Uprima® NPT Valueswith Values for Normals

- Maximum Tip RAU Values

- Note:	Data from Normals Extrapolated from Graph in Levine and Carroll,*Journal of Urology*, Vol. 152, 1103-1107, Oct. 1994.

*Maximum Tip Rigidity Activity Unit (RAU)*

- 

**®**

- %

- Patient Population

## Comparison of Uprima® NPT Valueswith Values for Normals

- Maximum Base RAU Values

- Note:	Data from Normals Extrapolated from Graph in Levine and Carroll,*Journal of Urology*, Vol. 152, 1103-1107, Oct. 1994.

*Maximum Base RAU*

- 

**®**

- %

- Patient Population

## Representative ED Patient Population Conclusion

- Reflective of the ED patient population as a whole including both organic and non-organic disease
- Clearly defined and relevant to clinical practice
- Consistent with the Viagra® patient population
- Consistent with MMAS
- Included patients with mild, moderate and severe ED
- RigiScans abnormal
- The patient population studied does support the proposed indication

- Patient Population

## Efficacy Endpoints

## Efficacy Endpoints for Phase III Studies

- Primary Endpoint
- Percent of patient “Yes” responses to the question:“Did you attain and maintain an erection firm enough for intercourse?”
- Secondary Endpoints
- Percent of partner “Yes” responses to the question:“Was the erection firm enough for intercourse?”
- Percent of patient/partner “Yes” responses to the question:“Did you have intercourse with your partner?”
- Time to erection

- Efficacy Endpoints

## Efficacy Endpoints for Phase III Studies

- Patient Brief Sexual Function Inventory (BSFI) data
- Partner Brief Sexual Function Inventory data
- Patient International Index of Erectile Function (IIEF) data

- Efficacy Endpoints

## Uprima®-Efficacy Endpoints

- Consistent
- Clear
- Relevant
- Rigorous

- Efficacy Endpoints

## Efficacy

- Crossover studies
- Primary endpoint (patient and partner)
- Subgroup analyses
- Validated questionnaires
- Diabetes
- Parallel study (M97-763)
- Long-term studies

- Results are shown from the 3 crossover studies combined, but the results from the individual
- studies are consistent with the combined data

## Crossover Study Schematic

- Open-Label
- Flexible Dose Long-Term Study

- Baseline

- 24-96 Hours
- Washout

- 2-4 Week
- Baseline

- 4 Week
- Treatment Period 1

- 4 Week
- Treatment Period 2

- Washout
- Period

- Washout
- Period

- 2 mg

- Placebo

- Placebo

- 2 mg

- Uprima®

- Uprima®

- Washout
- Period

- Washout
- Period

- Placebo

- 4 mg

- Placebo

- 4 mg

- Uprima®

- Uprima®

- Washout
- Period

- Washout
- Period

- Placebo

- 6 mg

- Placebo

- 6 mg

- Uprima®

- Uprima®

- Randomization

- Washout
- Period

- Washout
- Period

- Placebo

- 5 mg

- Placebo

- 5 mg

- Uprima®

- Uprima®

- Phase IIIM96-470, M97-658 & M98-941

- Efficacy-Crossover Studies

## Crossover Studies

- Suggested by the FDA and provided a powerful design
- Allows patients to be their own control
- All patients are exposed to study drug
- Appropriate for stable chronic diseases

- Rationale for Crossover Study Design

- Efficacy-Crossover Studies

## Patient Response (per attempt)“Erection Firm Enough for Intercourse”

- p<.001

- p<.001

- Patient Response (per attempt)“Erection Firm Enough for Intercourse”

- Phase III – CrossoverM96-470, M97-658 & M98-941

- p<.001

- %
- “Yes”

*Combined Data – Phase III Crossover Studies*

**®**

- Efficacy-Crossover

## Patient Response (per attempt) “Did Attempt Result in Intercourse”

- p<.001

- p<.001

- p<.001

- %
- “Yes”

- p<.001

- Phase III – CrossoverM96-470, M97-658 & M98-941

**®**

*Combined Data – Phase III Crossover Studies*

- Efficacy-Crossover

## Intercourse RatesComparison of Uprima® to Viagra®

- Uprima® vs. Viagra®

**Uprima****®**

**Viagra****®1**

- %

- %

- 1	Calculated from data provided in the Approval Package for Viagra® (Sildenafil Citrate). FDA.GOV/CDER/CONSUMERINFO/VIAGRA/VIAGRA/HTM. *Joint Clinical Review*. April 1999.

- Phase III Crossover Studies

- Phase III Studies

- Efficacy-Viagra

## Partner Responses

## Partner Involvement in Uprima® Studies

- Partner responses were a unique factor for the Uprima®  clinical trials
- Partner BSFI was developed, utilized and validated
- Partner consent and participation were required for all studies
- ED is a couple’s issue

- Efficacy-Crossover

## Partner Response (per attempt)“Erection Firm Enough for Intercourse”

- p<.001

- p<.001

- Partner Response (per attempt)“Erection Firm Enough for Intercourse”

- Phase III – CrossoverM96-470, M97-658 & M98-941

- p<.001

- %
- “Yes”

*Combined Data – Phase III Crossover Studies*

**®**

- Efficacy-Crossover

## Partner Response (per attempt) “Did Attempt Result in Intercourse”

- p<.001

- p<.001

- Partner Response (per attempt) “Did Attempt Result in Intercourse”

- p<.001

- %
- “Yes”

*Combined Data – Phase III Crossover Studies*

- Phase III – CrossoverM96-470, M97-658 & M98-941

**®**

- Efficacy-Crossover

## Primary Endpoint Subgroup Analyses

- Organic
- Non-organic
- Hypertensive Patients
- Diabetic Patients
- Coronary Artery Disease

- Benign Prostatic Hyperplasia
- Alcohol Users
- Smokers
- Age >65
- ED Severity

- Efficacy-Crossover/Subgroups

## Patient Response (per attempt)“Erection Firm Enough for Intercourse”

- Patient Response (per attempt)“Erection Firm Enough for Intercourse”

- Phase III – CrossoverM96-470, M97-658 & M98-941

- p<.001

- %
- “Yes”

*Subgroup: Documented Organic Disease**(Hypertension, CAD or Diabetes)*

**®**

- p<.001

- p<.001

- Efficacy - Subgroups

## Patient Response (per attempt) “Erection Firm Enough for Intercourse” 

- p=.002

- Patient Response (per attempt) “Erection Firm Enough for Intercourse”

- p<.001

- Phase III – Crossover M96-470, M97-658 & M98-941

- p<.001

- %
- “Yes”

*Subgroup: Age >65*

**®**

- Efficacy - Subgroups

## ED Severity

## Assessment of Effect of ED Severity on Efficacy

- Analyses were performed in patients with:
- mild, moderate and severe ED severity scores at baseline
- no success during baseline
- abnormal RigiScan scores at inclusion into study

- Efficacy - ED Severity

## Definition of ED Severity Based on IIEF

- ED severity was determined based on the sum of 6 questions from the IIEF (questions 1-5 and 15)
- 	    Severe	<10
- 	    Moderate	11-16
- 	    Mild	17-25
-         No ED	>25

- Efficacy-ED Severity

*IIEF Scoring For Erectile Dysfunction*

## Patient Response (per attempt)“Erection Firm Enough for Intercourse”

- p<.001

- p<.001

- Patient Response (per attempt)“Erection Firm Enough for Intercourse”

- Phase III – Crossover M97-658 & M98-941

- p<.001

- %
- “Yes”

*Erectile Dysfunction: Severe* **(39% of patients)*

**®**

- * IIEF scores: no ED >25, mild ED 17-25, moderate ED 11-16, severe ED <10.

- Efficacy-ED Severity

## Patient Response (per attempt) “Erection Firm Enough for Intercourse”

- Phase III – Crossover M96-470, M97-658 & M98-941

- p<.001

- %
- “Yes”

- p<.001

- p<.001

- p<.001

*For Patients (39%) With No Success During Baseline*

**®**

- Efficacy-ED Severity

## Patient Response (per attempt)“Erection Firm Enough for Intercourse”

- Patient Response (per attempt)“Erection Firm Enough for Intercourse”

- p=.008

- p=.002

- p<.001

- %
- “Yes”

- p=.001

**®**

- Phase III – Crossover

*Patients with Maximum Tip RAU ****9.5*

- Efficacy-ED Severity

## ED Severity Conclusion

- Uprima® is effective in patients with severe ED as 	evaluated by:
- Baseline IIEF ED severity
- Baseline success rate
- Abnormal NPT (Tip RAU 9.5)
- Uprima® is also effective in patients with mild or moderate ED

- Efficacy-ED Severity

## Other Endpoints

## Other Endpoints

- Home-Use (per attempt) Endpoints
- Timing of erections
- Treatment Success (% achieving erections sufficient for intercourse in >50% of attempts)
- Diary Satisfaction Scale (per attempt)
- Validated Questionnaires
- Partner Satisfaction Scale (PBSFI)
- IIEF (4 point improvement in erectile function)

- Efficacy-Other Endpoints

## Median Time to Erection (Using Only Attempts When an Erection Was Achieved)

- Median Time to Erection (Using Only Attempts When an Erection Was Achieved)

- Phase III – CrossoverM96-470, M97-658 & M98-941

- More erections occurred with Uprima® than with placebo.
- IQR = interquartile range.

*Combined Data – Phase III Crossover Studies*

**2 mg (271, 309)****	****16.3****	****(10 – 25)****	****17.5****	****(10 – 25)**
**4 mg (271, 318)****	****15.0****	****(9 – 25)****	****16.4****	****(10 – 28)**

- Efficacy-Other Endpoints

**Erection firm enough for intercourse 33.8% on placebo and 54.4% on 4 mg **
**Natural time course (in context of clinical trial)**
**Not dose related**

## Patient Assessment Percentage of Patients Deemed a Treatment Success

- %

- p<.001

- p<.001

- p<.001

- Definition of Success:	A treatment is deemed a “success” for a patient if at least 50% of all attempts  	while using the treatment resulted in erections firm enough for intercourse.

- p<.001

- Phase III – CrossoverM96-470, M97-658 & M98-941

**®**

*Combined Data – Phase III Crossover Studies*

- Efficacy-Other Endpoints

## Percent of Patients with Mean Intercourse Attempt Satisfaction >3 and an Improvement Over Baseline

- Phase III – Crossover M96-470, M97-658 & M98-941

- p<.001

- p<.001

- p<.001

- p<.001

**®**

*Combined Data – Phase II/III Studies*

**	****Scale:**
- 	1=Very dissatisfied
- 	2=Mostly dissatisfied
- 	3=Neutral or mixed (about     equally satisfied and dissatisfied)
- 	4=Mostly satisfied
- 	5=Very satisfied

- Efficacy-Other Endpoints

## Percent of Partners with Mean Intercourse Attempt Satisfaction >3 and an Improvement Over Baseline

- Phase III – Crossover M96-470, M97-658 & M98-941

- p<.001

- p<.001

- p<.001

- p<.001

**®**

*Combined Data – Phase II/III Studies*

**	****Scale:**
- 	1=Very dissatisfied
- 	2=Mostly dissatisfied
- 	3=Neutral or mixed (about     equally satisfied and dissatisfied)
- 	4=Mostly satisfied
- 	5=Very satisfied

- Efficacy - Other Endpoints

## Percent of Patients with 4 Point Improvement in the Erectile Function Domain Index of the IIEF

- p<.001

- Percent of Patients with 4 Point Improvement in the Erectile Function Domain Index of the IIEF

- p<.001

- Phase III – Crossover StudiesM97-658 & M98-941

- p<.001

- %

**®**

*Combined Data – M97-658 & M98-941*

- Based on a scale of 1 to 30, with higher scores being better.

- Efficacy-Other Endpoints

## Phase III Crossover Studies Conclusion

- Clinical significance has been shown at all dose strengths and demonstrated in all subgroups (organic, non-organic, hypertensive, etc.) with these endpoints
- The robustness of the Uprima® efficacy results has been demonstrated across a variety of home-use efficacy endpoints and is confirmed by the results of validated questionnaires

- Efficacy-Crossover

## Phase III Crossover Studies Conclusion (cont.)

- Clinical Relevance of 2 mg
- Statistically superior compared to placebo in all Phase III Crossover studies for the primary endpoint and virtually all secondary endpoints
- Shows a 4-point improvement on IIEF in 45% of patients (compared to 27% of placebo)
- Statistically significant compared to placebo in patients with moderate to severe ED as well as patients with a variety of organic diseases (hypertension, diabetes, CAD, etc.)
- Intercourse rates increase from a placebo rate of 29% to 42% for Uprima® 2 mg (13% increase) compared to 16% increase seen with Viagra® 25 mg

- Efficacy-Crossover

## Efficacy

- Crossover studies
- Diabetes
- Parallel study (M97-763)
- Long-term studies

## Diabetes Study Baseline ED Severity

**4 mg**
**n          (%)**

**5 mg**
**n         (%)**

**Baseline IIEF **
**Severity Rating***

**Severe****	****61****	****71.8****	****42****	****50.0****	****103****	****61.0**
**Moderate****	****20****	****23.5****	****24****	****28.6****	****44****	****26.0**
**Mild****	****  4****	****4.7****	****18****	****21.4****	****22****	****13.0**

**Combined****
**n          (%)**

*M97-804*

- 	*	Severity rating determined by Erectile Function total.
- 		Severity Score; Mild (17-25), Moderate (11-16), and Severe (<10).		Note: No NPT required for enrollment.
- 	**	Due to randomization imbalance, the 4 and 5 mg were combined to represent the overall diabetic population.

- Efficacy-Diabetes

## Patient Response (per attempt)“Did You Achieve an Erection Firm Enough for Intercourse”

- 5.1

- 12.2

- 8.1

- 14.5

- 27.2

- 20.4

- 24.6

- 34.1

- 28.9

- 0

- 10

- 20

- 30

- 40

- 50

- 4 mg (N=90)

- 5 mg (N=86)

- Combined (N=176)

- Baseline

- Placebo

- Uprima®

- Patient Response (per attempt)“Did You Achieve an Erection Firm Enough for Intercourse”

- Phase III – Diabetic

- p=.020

- p=.179

- %
- “Yes”

- p=.009

*M97-804*

- Efficacy-Diabetes

## Patient Response (per attempt) “Erection Firm Enough for Intercourse”

- p=.038

- p=.021

- 19.6

- 6.4

- 13.4

- 11.5

- 22.4

- 18.3

- 25.9

- 30.0

- 40.3

- 29.2

- 36.2

- 45.2

- 0

- 10

- 20

- 30

- 40

- 50

- 2 mg (N=30)

- 4 mg (N=113)

- 5 mg (N=111)

- 6 mg (N=8)

- Baseline

- Uprima®

- p=.004

- %
- “Yes”

- p=.090

- Patient Response (per attempt) “Erection Firm Enough for Intercourse”

- Phase III – Crossover M96-470, M97-658, M98-941 & M97-804

*Diabetic Patients– Phase III Crossover Studies**(M96-470, M97-658, M98-941 & M97-804)*

- Efficacy-Diabetes

- Placebo

## Diabetes Efficacy Conclusion

- Similar to the results seen in the Viagra® studies, efficacy in diabetic patients is lower than seen in the general population
- Although there was a randomization imbalance, statistically significant results were noted in the 4 mg arm and both dosing groups combined from the M97-804 Diabetes Study
- In diabetic patients enrolled in the Phase III Crossover studies, efficacy improved approximately 10-20% over placebo in all dose strengths

- Efficacy-Diabetes

## Uprima® Efficacy

- Crossover studies
- Diabetes
- Parallel study (M97-763)
- Long-term studies

## Parallel Study Schematic Design

- Open-Label
- Long-Term Extension Study

- Placebo

- 6 mg

- Baseline

- Baseline
- 2-4  Weeks

- Day 1

- 5 mg

- Informed Consent

- Randomization

- Placebo

- 6 mg Fixed Dose VOLUNTARY TITRATION

- 5 mg Fixed Dose

- Week 1

- Week 2

- Week 3

- Week 4

- Week 8

- 2 mg

- 4 mg

- 5 mg

- 6 mg

- Optimal Dose

- Phase III – ParallelM97-763

- Efficacy-Parallel

## Patient Response (per attempt)“Erections Firm Enough for Intercourse”

- Average Percent

- p<.001

- p<.001

- p<0.001

- N=114

- N=112

- N=112

- N=114

- N=84

- N=82

- N=232

- N=230

- N=230

- N=232

- 2, 4, 5, 6 mg

- 2, 4 mg

- p=.003

- Phase III – ParallelM97-763

- Patient Response (per attempt)“Erections Firm Enough for Intercourse”

**®**

- Based on last 8 attempts.

*M97-763*

- Efficacy-Parallel

## Partner Response (per attempt)“Erections Firm Enough for Intercourse”

- p<.001

- p<.001

- p=.002

- N=112

- N=112

- N=114

- N=112

- N=80

- N=84

- N=225

- N=228

- N=228

- N=224

- 2, 4, 5, 6 mg

- 2, 4 mg

- p=.004

- Phase III – ParallelM97-763

- Partner Response (per attempt)“Erections Firm Enough for Intercourse”

- Based on last 8 attempts.

*M97-763*

- Average Percent

**®**

- Efficacy-Parallel

## Patient Response (per attempt)“Did Attempt Result in Intercourse”

- p<.001

- p<.001

- p=.003

- N=114

- N=112

- N=112

- N=114

- N=84

- N=82

- N=232

- N=230

- N=230

- N=232

- 2, 4, 5, 6 mg

- 2, 4 mg

- p=.005

- Phase III – ParallelM97-763

- Patient Response (per attempt)“Did Attempt Result in Intercourse”

- Based on last 8 attempts.

*M97-763*

- Average Percent

**®**

- Efficacy-Parallel

## Efficacy

- Crossover studies
- Diabetes
- Parallel study (M97-763)
- Long-term studies

## Discontinuations in Long-Term Studies

## Long-Term Studies

- The long-term studies were designed primarily to collect safety information
- A number of factors contributed to patient discontinuation in the long-term studies
- Lack of efficacy
- Adverse events
- Approval of new compounds (MUSE®, Viagra®)
- Length of studies and stringent patient requirements (office visits, diary completion after every attempt, etc.)
- Competing investigational studies

- Efficacy-Long -Term

## Percentage of Erections Firm Enough for Intercourse

- Phase III – Long-Term Open-LabelM96-471, M97-659, M97-682 & M98-936

- N=1,008

- N=887

- N=728

- N=599

- N=492

- N=426

*All Doses (2, 4, 5, and 6 mg)*

- N=1,019

- Efficacy-Long -Term

## Long-Term Studies

- Short-term studies show that treatment success is achieved in 50-60% of patients, yet approximately 80% of eligible patients enrolled into long-term studies
- Dropout rates of 20-30% are not unexpected based on the number of patients who enrolled from the short-term studies who had no efficacy
- Dropout rates were also influenced by adverse events, approval of Viagra®, other competing ED trials and the burden of patient inconvenience associated with frequent visits, diary completion, etc.
- Despite this, over 42% of patients reached the 6-month time point in the long-term studies and demonstrated sustained and reliable efficacy

- Efficacy-Long -Term

## Percentage of Erections Firm Enough for Intercourse

- Phase III – Long-Term Open-LabelM96-471, M97-659 & M97-682

- N=417

- N=425

- N=422

- N=425

- N=426

- N=426

*All Doses (2, 4, 5, and 6 mg)*

- Includes only patients who remained on drug for at least 6 months.

- N=426

- Efficacy-Long -Term

## Percentage of Erections Firm Enough for Intercourse

- Phase III – Long-Term Open-LabelM96-471, M97-659 & M97-682

- N=126

- N=123

- N=117

- N=117

- N=125

- N=128

*2 and 4 mg*

- N=129

- Includes only patients who remained on drug for at least 6 months.

- Efficacy-Long -Term

## Efficacy in Long-Term Studies Conclusion

- Patients remaining in long-term studies have sustained and reliable response with erections in more than 80% of attempts
- Patients obtaining efficacy in the long-term studies are similar to all Uprima® patients as evidenced by their baseline success rates

- Efficacy - Long -Term

## Overall Efficacy Conclusions

## Overall Efficacy Conclusions

- Clinical trials included patients representative of the general ED population, similar to Viagra® and MMAS
- Uprima® 2 and 4 mg has been shown to be statistically and clinically significantly better than placebo in large scale controlled studies
- Uprima® 2 and 4 mg have demonstrated a clinically relevant improvement in the IIEF Erectile Function Domain (4-point) compared to placebo
- Uprima® partner efficacy data has been shown to be almost identical to Uprima® patient efficacy data
- Patients remaining in the long-term studies have substantial and reliable responses with erections in more than 80% of attempts

- Efficacy-Conclusions

## Overall Efficacy Conclusions (cont.)

- Uprima® efficacy has been demonstrated in subsets of patients with:
- organic disease			 - benign prostatic hyperplasia
- hypertension			 - alcohol users
- diabetes				 - smokers
- coronary artery disease
- Uprima® efficacy has been demonstrated in all severities of ED
- Uprima® has been shown to have a rapid onset of erectile response
- Uprima® has demonstrated significance in all satisfaction and erectile function indices (BSFI, IIEF, Partner BSFI)

- Efficacy-Conclusions