Indacaterol is Novartis's long-acting beta agonist (LABA) for use in the treatment of chronic obstructive pulmonary disease (COPD). EMEA approved the drug for use in Europe where it is marketed as Onbrez™. However, FDA issued a Complete Response Letter last October, apparently raising concerns related to the proposed dosing regimen. Novartis has not disclosed any details about the FDA letter, but initiated several new studies since receiving it. This report explores the likely reasons for the FDA action, as well as probable routes and timelines to resolution, including an in depth assessment of the history of safety issues associated with LABAs and their potential impact on indacaterol’s approvability. The report also reviews the COPD market and competitive landscape, as well as indacaterol’s commercial prospects.

Published: July 7th, 2010

Number of pages: 58

Authors: Dr. Ellen Brady and Dr. Ilana Fogelman

TABLE OF CONTENTS:
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INTRODUCTION
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1. Chronic Obstructive Pulmonary Disease
- Clinical picture
- Epidemiology
- Current treatments

THE INDACATEROL (QAB149) PROGRAM
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1. Pharmacology
2. Phase I/II
3. Phase II
4. Phase III
- The INHANCE trial (B2335S)
- The INVOLVE Study (B2334)
- Study B2346 (INLIGHT, n=416)
- Other indacaterol studies
- Studies initiated after FDA's issuance of a Complete Response Letter

CLINICAL AND REGULATORY DISCUSSION
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1. Does the indacaterol program meet standards set by current guidance?

a. Indications and their endpoints
- Improving airflow obstruction:
- Symptom relief:
- Modification or prevention of exacerbations
- Alteration of disease progression:
- Alteration of lung structure
b. Dose finding
c. Duration and number of efficacy trials
d. Other design considerations for efficacy trials
e. Does the indacaterol NDA measure up to this and other relevant guidance?

2. What about the dose selection?

3. Could LABA-related safety issues drive FDA concerns?
a. Historical background on LABA safety issues
b. Subsequent FDA Advisory Panels
c. FDA's February 18, 2010 release

4. What are the implications for indacaterol?
a. Cardiovascular safety as a separate issue
5. In summary

MARKET ISSUES
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1. Market overview
2. Competitive concerns
3. Novartis’s pipeline products may address competitive concerns
- Indacaterol + mometasone furoate combination (QMF149)
- Glycopyrrolate (NVA237) is a long-acting anti-muscarinic
- NVA237 + indacaterol (QVA149)
4. Several other long-acting β-agonists are in the pipeline
- Carmoterol (Chiesi)
- Relovair (Theravance/GSK):
- Olodaterol (Boehringer-Ingelheim):
- LAS100977 (Almirall/Forest Laboratories):
- AZD3199 (AstraZeneca):
- PF-00610355 (Pfizer):
5. Other pipeline products
- Eklira (Almirall/Forest Laboratories):
- Daxas (Nycomed/Forest Laboratories):
- Formoterol + mometasone (Schering-Plough/Merck):

SUMMARY OPINION
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1. Most probable issue(s) driving FDA’s Complete Response Letter
2. Indacaterol’s competitive prospects
3. Most likely approval timeline