# Presentation: 909165

## EXUBERA®(insulin [rDNA origin] powder for inhalation)

*Endocrinologic and Metabolic Drugs**Advisory Committee Meeting**September 8, 2005**Dr. Neville Jackson *

## Agenda

|   Dr. Neville Jackson |  Introduction |
| --- | --- |
|   Dr. Anne Cropp |  Overview of Clinical Program |
|   Dr. William Cefalu |  Medical Need |
|   Dr. Neville Jackson | Benefit and Managing the Risk |
|  |  |

## Attending Experts

| William Cefalu, MD
Professor and Chief, Division of Nutrition and Chronic Diseases
Pennington Biomedical Research Center, LSU System | Tim Heise, MD
Chief Executive Officer
Profil Institute for Metabolical Research, Neuss, Germany |
| --- | --- |
| Edwin Fineberg, MD
Emeritus Professor of Endocrinology and Metabolism 
Indiana University School of Medicine | Claudio Cobelli, PhD
Professor of Biomedical Engineering
University of Padua, Italy |
| Joseph Brain, S.D.
Professor of Environmental Physiology
Harvard School of Public Health | Gary Williams, MD
Professor of Pathology
New York Medical College |
| Richard Ahrens, MD
Professor of Pediatrics, Pediatric Allergy and Pulmonary Division
University of Iowa | Marcia Testa, MPH, MPhil, PhD
Senior Lecturer on Biostatistics
Harvard School of Public Health |

**Christine T Rathbun:**
**This needs to replace slide 3 after Mock III**

## The Diabetes Epidemic

**Prevalence of diagnosed diabetes increased 40% from 4.9% in 1990 to 6.9% in 1999**
**Estimated lifetime risk of developing diabetes for individuals born in 2000 is 32.8% for males and 38.5% for females**
**If diagnosed at age 40, men will lose 11.6 years and 18.6 quality-adjusted-life-years. Women will lose 14.3 years and 22 quality-adjusted-life-years**

- Source: Narayan KMV, Boyle JP, Thompson TJ, et al.
- Lifetime Risk for Diabetes Mellitus in the United States JAMA. 2003;290:1884-90.

## Glycemic Control is Sub-optimal

**Insulin is the most effective treatment for diabetes and mandated for type 1 patients **
**67% of type 2 diabetes patients in United States are not achieving target glycemic control**
**Insulin therapy is initiated too late in type 2 diabetes patients**
**Intensive insulin therapy is underutilized in both type 1 and type 2 diabetes patients**

## Video

- Video Describing the Inhaler and How to Use the Inhaler Shown

## Inhaled InsulinProposed Indication and Usage

**Treatment of adult patients with diabetes mellitus for the control of hyperglycemia **
- Combination therapy with intermediate/         long-acting SC insulin or oral agents
- Monotherapy (type 2)

## Clinical Development Program

**Clinical Development Program**

**IND 43313 **

**NDA **

**EOP 2 **

**Phase 2 **

**Phase 3         Group I**

**Phase 1 **

**102 **

**103 **

**104 **

**1036 **

**102 E**** **

**103 E **

**104 E **

**Phase 1 Studies**** ****Developmental**

**1001/1002**

**106 **

**108 **

**110 **

**107**** **

**109 **

**1009**

**111 **

**1026 **

**1027**

**1022****   ****1029 **

**1017**

**1028  1030**

**Phase 1 Studies Final Formulation**

**FDA Interactions**

**Pre-NDA **

**Phase 3 **
**Group II**

**Phase 3b**

**Exploratory**

**Efficacy **

**Long-term Safety **

## Assessment of Pulmonary Function

**> 43,000 PFT measurements performed in > 4000 adult subjects**
**Characterized PFT changes and reversibility in short- and long-term studies**

## The Inhaled Insulin Clinical Development Program

**Efficacious as short-acting SC insulin **
**Provides long-term glycemic control**
**More patients preferred INH to previous therapy**
**Safety profile characterized**
- Well tolerated, hypoglycemia comparable to injected insulin
- Insulin antibodies
- Small, early, non-progressive, reversible declines in FEV1 and DLco
- Mechanism unknown but under continued exploration

## Agenda

|   Dr. Neville Jackson |  Introduction |
| --- | --- |
|   Dr. Anne Cropp |  Overview of Clinical Program |
|   Dr. William Cefalu |  Medical Need |
|   Dr. Neville Jackson | Benefit and Managing the Risk |
|  |  |

## Slide 12