癌治療薬パイプライン：将来の標的療法

Abstract

Introduction

Drug companies' cancer pipelines are bulging, and hundreds of new drugs are in development-the modern equivalent of a gold rush. Remarkable successes have been recorded with targeted oncology, but the treatment of more than 200 types of cancer remains a daunting task. Today' s three principal modalities of cancer treatment-surgery, radiotherapy, drug treatment-have begun to give way to new targeted techniques. Genentech/Roche/Chugai' s Herceptin and ten other blockbuster “targeted” therapies have shown that drugs designed to interact with specifi c molecular targets can hit cancer where it hurts. However, targeted therapies are no panacea; to continue advancing cancer treatment, investigators must continue to improve their understanding of specifi c drug targets and continue to explore gene regulation and protein networks, to which targeted oncology therapies owe their existence.

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• In 2007, there were 11 highly successful targeted cancer blockbusters. Which drugs were they, and which blockbusters also carried a strong warning label: namely, the dreaded “black box” authorized by the FDA?
• Amgen recently suffered several setbacks, including unfavorable trial results from a Phase III trial of Vectibix in fi rst-line, metastatic colorectal cancer. But Amgen still has upward of 60 ongoing development programs. Why is this company still in need of a more vibrant pipeline?
• Bristol-Myers Squibb has a solid presence in targeted oncology drugs with its blockbuster drug Erbitux. Which other drug in Bristol-Myers Squibb' s portfolio represents a signifi cant achievement in the rational design of drugs to overcome drug resistance in cancer?
• With Avastin, Herceptin, and Rituxan/MabThera, Genentech and Roche are on track to rack up more than $11 billion in combined worldwide revenues in 2007. Competition is on the way, however. Which companies have drugs in Phase III trials for non-small-cell lung cancer? What are Genentech/Roche' s strategies for expanding their prolifi c oncology franchise?
• For the last few years, ImClone has been sidetracked by legal issues; yet ImClone still claims a legitimate cancer blockbuster: Erbitux, the fi rst targeted cancer therapy approved for colorectal cancer. Why have unfavorable results of Amgen' s Vectibix made clinicians, investigators, and investors anxious about Erbitux' s future potential?
• Much excitement accompanied the completion of sequencing the human genome, circa 2000. But the excitement soon gave rise to somber refl ection: the sequencing itself did not immediately point the way to a bevy of new oncology drugs. What work still needs to be done for human genome sequencing to realize its promise of helping to provide personalized, targeted cancer therapies? Scope

Scope

• Cancer therapy today and tomorrow: limitations of the three principal modalities of current cancer treatment; addressing unmet needs; targeted cancer therapy and personalized medicine; changes in the drug development paradigm.
• Leaders in oncology: the world' s best-selling oncology drugs and the key products in 11 leading oncology franchises.
• Oncology pipelines: Amgen' s woes; AstraZeneca' s disappointment; Bristol-Myers Squibb' s expansion; Exelixis' s aggressive discoveries; Genentech/Roche' s leading oncology franchise; Genmab' s waves; GlaxoSmithKline' s oncological advances; ImClone' s legitimate blockbuster; ImmunoGen' s “armed” technology; Novartis' s kinase inhibitors; Pfi zer' s bandwagon-jumping.
• Waves of the future: human genome sequencing; the oncology gold rush; RNA targeted therapies.
• Spectrum expert commentaries: two separate commentaries in which leading oncology experts

Table of Contents

• Executive Summary
  • Strategic Considerations
  • Stakeholder Implications
• Cancer Therapy Today and Tomorrow
• Targeted Therapy-Hitting Cancer Where it Hurts
• Leaders in Oncology
• Today' s Reality-Diffi culties in Developing Targeted Therapies
  • Toxicities and Black Box Warnings
  • Personalized Medicine
    • Murphy' s Law in Effect
    • Key Products in Development
  • AstraZeneca' s Initial Disappointment Gives Rise to Changes
  • Bristol-Myers Squibb Expands into Biologics
  • Exelixis Engages in Aggressive Drug Discovery and Development
    • Third-Party Clinical Financing Vehicle
    • Small-Molecule Kinase Inhibitors
  • Genentech/Roche Lead the Way with Oncology Biologics
  • Genmab Makes Waves with Largest European Product Deal Ever
  • GlaxoSmithKline Advances into Herceptin' s Space in Breast Cancer
  • ImClone Faces Ongoing Strife but Boasts a Legitimate Blockbuster
  • ImmunoGen Innovates with Armed Antibody Technology
  • Novartis Banks on Small-Molecule Kinase Inhibitors
  • Pfi zer Moves Beyond Historical Reliance on Small-Molecule Drug Technologies
• Waves of the Future
  • Somber Refl ection on Human Genome Sequencing
  • Mainstay Cancer Treatment Circa 2015
  • Personalized Targeted Therapies
  • Tomorrow' s RNA Targeted Therapies

Spectrum Expert Commentaries:

• “Targeted Oncology Therapy: Trend Toward Personalized Treatment,” by David Z. Chang, M.D., Ph.D., Gastrointestinal Medical Oncology & Immunology, The University of Texas, M.D. Anderson Cancer Center
• “The Potential of MicroRNA Modulators as Targeted Oncology Therapies,” by Fabricio F. Costa, Ph.D., Cancer Biology and Epigenomics Program, Children' s Memorial Research Center, Northwestern University' s Feinberg School of Medicine, and Thomas Wurdinger, Ph.D., Molecular Neurogenetics Unit, Department of Neurology, Massachusetts General Hospital, and Program in Neuroscience, Harvard Medical School

Tables:

• 1. Amgen' s Targeted Oncology Pipeline-Select Products, 2007
• 2. AstraZeneca' s Targeted Oncology Pipeline-Select Products, 2007
• 3. Bristol-Myers Squibb' s Targeted Oncology Pipeline-Select Products, 2007
• 4. Exelixis' s Targeted Oncology Pipeline-Select Products, 2007
• 5. Genentech and Roche' s Combined Targeted Oncology Pipeline-Select Products, 2007
• 6. Genmab' s Targeted Oncology Pipeline-Select Products, 2007
• 7. GlaxoSmithKline' s Targeted Oncology Pipeline-Select Products, 2007
• 8. ImClone' s Targeted Oncology Pipeline-Select Products, 2007
• 9. ImmunoGen' s Targeted Oncology Pipeline-Select Products, 2007
• 10. Novartis' s Targeted Oncology Pipeline-Select Products, 2007
• 11. Pfi zer' s Targeted Oncology Pipeline-Select Products, 2007

Figures:

• 1. Leading Sites of New Cancer Cases and Deaths-2007 Estimates
• 2. Considerations for Successful Anticancer Drug Development
• 3. Best-Selling Oncology Products, 2006 and 2012
• 4. Leading Oncology Franchises-Key Products, 2006
• Expert Commentary. Epidermal Growth Factor Receptor Targeted Drugs