近年の安全問題とぺリオキシソーム増殖因子活性受容体（PPAR）ガンマ作動薬

Abstract

Introduction

The peroxisome proliferator-activated receptor (PPAR)-gamma agonist class of drugs is the fastest-growing drug class in the type 2 diabetes market. Sales of the two PPAR-gamma agonists, GlaxoSmithKline' s Avandia and Takeda' s Actos, are signifi cant drivers of type 2 diabetes market sales. However, a recent study has questioned the safety of Avandia and has triggered a debate about the use of PPAR-gamma agonists, thereby presenting commercial opportunities for new agents in the treatment of type 2 diabetes.

Questions Answered in This Spectrum Report

• PPAR-gamma agonists are among the most popular therapies in the treatment of type 2 diabetes. However, a recent meta-analysis has highlighted the potential for cardiovascular side effects with Avandia and has affected both sales of the agent and GlaxoSmithKline' s stock price. What are the strengths and weaknesses of the Avandia study? Are the safety concerns raised by the study relevant only to Avandia or to the entire PPAR-gamma agonist class?
• The safety concerns about PPAR-gamma agonists present a commercial opportunity for new agents that offer a unique mechanism of action, an improved safety profi le, and evidence of effi cacy. Which newly launched agents threaten to compete with the PPAR-gamma agonists for the position of preferred third-line therapy in type 2 diabetes? What advantages-and shortcomings-do these new agents have?
• Novartis is developing a drug that that promises to compete heavily with newly launched agents and further change the landscape of the type 2 diabetes market. How will this agent differentiate itself from the currently available type 2 diabetes therapies?

Scope

• Overview of PPAR-gamma agonists: mechanism of action, side effects, role in the treatment of type 2 diabetes.
• Avandia controversy: safety concerns, the response to the recent meta-analysis, implications for the PPAR-gamma agonist drug class.
• Commercial opportunities for new agents: description of agents that are newly launched or in development.
• Outlook: how recent developments will affect the PPAR-gamma agonist drug class and the type 2 diabetes market.

Table of Contents

• Executive Summary
  • Strategic Considerations
  • Stakeholder Implications
• Introduction
• An Overview of PPAR-Gamma Agonists
  • Mechanism of Action
  • Side Effects of PPAR-Gamma Agonists
  • PPAR-Gamma Agonists in the Treatment of Type 2 Diabetes
  • PPAR-Gamma Agonists in the Type 2 Diabetes Market
• The Controversy Surrounding Avandia
  • New Concerns Arise Over Avandia Use
  • Response and Repercussions
  • Are the Cardiovascular Risks a Class Effect?
• Do Avandia' s Safety Concerns Represent a Commercial Opportunity?
  • The Incretin Pathway
  • Eli Lilly/Amylin' s Byetta
  • Merck' s Januvia
• Outlook for PPAR-Gamma Agonists and the Type 2 Diabetes Market

Sidebar/Expert Commentary

• How Important Is Avandia to GlaxoSmithKline?
• Greater Transparency Needed for Clinical Trial Results

Tables

• 1. Results from Large-Scale Trials Involving Avandia

Figures

• 1. Mechanism of Action for PPAR-Gamma Agonists
• 2. Worldwide Sales of PPAR-Gamma Agonists, 1999-2006
• 3. Results from a Meta-Analysis of Trials Involving Avandia
• 4. Incretin Pathway
• 5. Growth of Key Drug Classes in the Type 2 Diabetes Market, 1999-2006
• 6. Comparison of Sales for Actos and Avandia, 1999-2006