NDA 21-272 Remodulin™ (treprostinil sodium) Injection

8/21/01


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Table of Contents

NDA 21-272 Remodulin™ (treprostinil sodium) Injection

Presentation and Speakers

Additional Representatives for Treprostinil

Pulmonary Arterial Hypertension

Symptoms of PAH

Commonly Used Treatments for PAH

Epoprostenol

Treprostinil Sodium

Development Rationale

Epoprostenol Delivery System

Treprostinil Delivery System

Epoprostenol vs. Treprostinil

Clinical Development

Pilot Study P01:03 Efficacy Results - Change from Baseline

P01:04 and P01:05 International, Multicenter, Double-Blind, Placebo-Controlled Trial Program (40 Centers)

Entry Criteria

Study Design

Efficacy Measures

6-Minute Walk Test

Symptoms and Signs

Symptoms and Signs

Dyspnea-Fatigue Rating

Dyspnea Fatigue Rating Magnitude of Task

Hemodynamic Measurements

Quality of Life (Minnesota Questionnaire)

Prespecified Endpoints

Statistical Analysis

Pre-specified Primary Analysis Plan

Baseline Characteristics Study 04/05

Baseline Characteristics Study 04/05

Baseline Hemodynamics Study 04/05

Baseline Treatment Study 04/05

Dosing Principles Study 04/05

PPT Slide

Effect of Treprostinil on 6-Minute Walk Distance at Weeks 1, 6, 12 (Placebo-Corrected; Study 04/05)

Change in 6-Minute Walk Distance Week 12

PPT Slide

PPT Slide

Time to Initiation of epoprostenol Discontinuation due to AE vs Deterioration Since discontinuation

Survival Distribution Since Discontinuation

PPT Slide

PPT Slide

PPT Slide

Distribution of Exercise Responses at Week 12 Study 04/05

Influence of Baseline Walk on 6-Minute Walk Distance at Week 12 Study 04/05

Influence of NYHA Class on 6-Minute Walk Distance Study 04/05

Severity of Dyspnea During Exercise Borg Dyspnea Score

Effect of Treprostinil on Distance and Symptoms During 6-Minute Walk Test (Placebo-Corrected, Study 04/05)

Cumulative Frequency Distribution Analysis of Distance and Symptoms During 6-Minute Walk Test (Study 04/05, Week 1)

Cumulative Frequency Distribution Analysis of Distance and Symptoms During 6-Minute Walk Test (Study 04/05, Week 6)

Cumulative Frequency Distribution Analysis of Distance and Symptoms During 6-Minute Walk Test (Study 04/05, Week 12)

PPT Slide

Signs and Symptoms of PAH Composite Score

Individual Symptoms Any Time During Double-Blind Therapy Compared With 4 Weeks Prior to Randomization

Individual Symptoms Last 6 Weeks of Double-Blind Therapy Compared With 4 Weeks Prior to Randomization

Syncope

Dyspnea Fatigue Score

Magnitude of Task Change from Baseline Percent of Patients Study 04/05

Patients Experiencing Clinical Deterioration (Prespecified Analysis) Study 04/05

Patients Experiencing Clinical Deterioration (Expanded Analysis) Study 04/05

Hospitalizations Study 04/05

Hemodynamic Effect Week 12 Study 04/05

Quality of Life (Minnesota Scale) Study 04/05

PPT Slide

Long-term Effects on 6-minute Walk (Study P01:06)

Efficacy Conclusions

Treprostinil Safety Experience/Exposure

Duration of Exposure (As of Oct. 1, 2000)

Doses of Treprostinil Used During Long-term Treatment

Adverse Events Reported by ᡂ% of Patients

Adverse Events Reported by ᡂ% of Patients

Adverse Events Reported by ᡂ% of Patients

Adverse Events by Dose at First Onset

Adverse Events by Duration of Treatment

Serious Adverse Events

Adverse Events Leading to Discontinuation

Local Infusion Site Pain and Reaction

Infusion Site Treatments Prescribed to ᡌ% Patients Study 04/05

Prescribing of Narcotic Analgesics

Infusion Site Pain Treatment Prescribed Narcotic Analgesics

Use of Narcotic Analgesics Study 06 Survey (535 of 545 patients)

Other Safety Considerations

PPT Slide

Risks of Epoprostenol Therapy

Treprostinil

Benefits of Treprostinil

Relation of Benefits to Risks of Treprostinil

PPT Slide

Author: Teresa Bongartz