Targacept is developing TC-5214 for adjunctive use in major depressive disorder. It is a selective neuronal nicotinic receptor antagonist and the S-isomer of mecamylamine (Inversine), a drug previously marketed for use in resistant hypertension. This report reviews phase II data and the probability that phase III trials will show efficacy. Although Chantix (indicated for smoking cessation) and Wellbutrin/Zyban (indicated for depression/smoking cessation) also impact this receptor family, TC-5214's pharmacology is unique enough that those experiences may not fully predict FDA's response to this novel agent. If successful, the adjunctive therapy niche seems promising. To date, only Abilify and Seroquel, two atypical antipsychotics compete in that space. However, many novel agents are in the pipeline and thus competition will be stiff.

Published: April 21st, 2010

Number of pages: 42

Authors: Ellen Brady, MD, MPH, and Ilana Fogelman, MD, MPH

TABLE OF CONTENTS


BACKGROUND
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1. Depression
- Clinical Picture
- Epidemiology
- Disease Mechanisms
- Current Treatment Paradigms
- Where Will Neuronal Nicotinic Receptors (Nnrs) Fit In This Picture?

Tc-5214
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1. Preclinical Profile
2. Clinical Data
- Mecamylamine
- Tc-5214 --Phase Iib

CLINICAL AND REGULATORY DISCUSSION
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1. Guidance Documents And Precedents Provide Insight Into FDA Thinking
2. What Nnr-Specific Issues Are Likely To Surface?
- Chantix As Precedent
- Bupropion (Wellbutrin And Zyban) As Precedent
- Other Potential Uses Suggest Opportunity And Risk

MARKET ISSUES
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1. Overview
2. The Adjunctive Therapy Niche
3. Pipeline

SUMMARY OPINION
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