Monoclonal Antibodies: Pipeline Analysis and Competitive Assessment

In the nearly 35 years since the first process for creating mAbs was introduced, they have remained a centerpiece of the growing biotechnology industry. Thirty therapeutic mAbs have been approved around the world, including 23 in the United States. A number of these drugs have attained blockbuster status, with sales reaching the coveted billion-dollar mark and well beyond. Rituxan, Remicade, Avastin, Herceptin, and Humira alone generated...

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In the nearly 35 years since the first process for creating mAbs was introduced, they have remained a centerpiece of the growing biotechnology industry. Thirty therapeutic mAbs have been approved around the world, including 23 in the United States. A number of these drugs have attained blockbuster status, with sales reaching the coveted billion-dollar mark and well beyond. Rituxan, Remicade, Avastin, Herceptin, and Humira alone generated sales of over $4 billion each in 2008, and global sales for this entire sector surpassed $30 billion last year.

Key challenges and implications presented in this new report include:

• Future products and their indications
• Merits of human versus chimeric structures
• Costs of mAb therapy and the US healthcare debate
• Clinical pipeline with over 250 candidates
• A focus on "engineered" antibodies

Monoclonal Antibodies: Pipeline Analysis and Competitive Assessment reviews the broad drug development effort that is focused on bringing improved mAb-based products to the market, concentrating on those used for therapeutic applications. It surveys the latest technologies being applied to the development of these compounds and profiles the major companies, drugs, and projects. It then draws conclusions about the future market potential for mAbs and discusses the major challenges faced by the industry.

The biotech industry devoted years to reducing the immunogenicity of mAbs, developing the technologies—detailed in this report—to progress from chimeric, to humanized, to fully human antibodies. These succeeding generations of mAbs have demonstrated incremental improvements in safety and activity, and the industry is currently in the middle of a major shift toward humanized and human products.

Much work has also been done on altering antibodies’ outward form to boost their efficacy, enabling them to more readily penetrate tumors, enhancing their ability to stimulate beneficial immune responses, or otherwise improving their characteristics. Into this realm fall such constructions as antibody fragments, diabodies, synthetic antibodies, bispecific antibodies, and antibody conjugates. This report looks at some of the engineered forms of antibodies and the companies that are leading the way in this research. Other complementary technologies, such as PEGylation and glycosylation, are also presented.

Monoclonal Antibodies: Pipeline Analysis and Competitive Assessment presents an analysis for the current state of mAb drug development. It identifies more than 250 therapeutic products now in clinical trials, which are largely concentrated in the areas of cancer, immunological and inflammatory diseases, as well as infectious diseases. Beyond these, hundreds more candidates are at the preclinical stage of development. Reviewed here are the products that are already available, those in clinical development, and those still at the preclinical stage that are likely to play an important role in the advancement of the field.

Please note, this report is delivered as a zip file.  
 

Pharmaceutical Industry in North America

Executive Summary

Chapter 1

BACKGROUND AND SCIENTIFIC OVERVIEW:

ANTIBODIES AND MONOCLONAL ANTIBODIES

1.1. What Is an Antibody?

1.2. What Is a Monoclonal Antibody?

Chapter 2

CURRENT AND EMERGING TECHNOLOGIES:

IMPROVING MONOCLONAL ANTIBODY

DESIGN AND PRODUCTION

2.1. Key Breakthroughs in the First 35 Years of Monoclonal Antibody

Development

Murine-Derived Monoclonal Antibodies

Chimeric Monoclonal Antibodies

Humanized Monoclonal Antibodies

Fully Human Monoclonal Antibodies

Antibody Fragments

Antibody Conjugates

2.2. Monoclonal Antibody Libraries and Display Technologies

Phage Display

MedImmune (AstraZeneca)

Dyax

Crucell

MorphoSys

Affitech

Biosite (Inverness Medical Innovations)

Affimed Therapeutics

XOMA

Ribosome Display

MedImmune (AstraZeneca)

Discerna

Other Library-Based Technologies

Alexion Pharmaceuticals

BioInvent International

viii • www.InsightPharmaReports.com • Reproduction prohibited

Table of Contents

Adimab

MSM Protein Technologies

Vaccinex

Morphotek (Eisai Corp. of North America)

AnaptysBio

Sorrento Therapeutics

2.3. Other Technologies for Designing Monoclonal Antibodies

Techniques for Improving Hybridoma Production

Abeome

New Techniques for Generating Animal-Derived Monoclonal

Antibodies

GENOVAC (Aldevron)

Epitomics

North Coast Biologics

Xori

Chiome Bioscience

Humanization Technology

Abmaxis (Merck)

Arana Therapeutics

MRC Technology

ImmunoGen

KaloBios Pharmaceuticals

PDL BioPharma

XOMA

Antitope

Xencor

Massachusetts Institute of Technology

Transgenic Mice

Amgen

Medarex

AVANIR Pharmaceuticals

Regeneron Pharmaceuticals

Human Hybridoma Technology

Morphotek (Eisai Corp. of North America)

Patrys

Kenta Biotech

2.4. Alternative Antibody Formats

Antibody Fragments

ESBATech

MacroGenics

Genmab

Synthetic Antibodies

Ablynx

Affibody

Domantis (GlaxoSmithKline)

AdAlta

Enzon Pharmaceuticals/Micromet

Arana Therapeutics

Bispecific Antibodies

Elusys Therapeutics

Monoclonal Antibodies: Pipeline Analysis and Competitive Assessment

Micromet

TRION Pharma

Affimed Therapeutics

Affitech/Pharmexa

Biotecnol

Other Antibodies That Enhance Effector Function

BioWa

MacroGenics

Tolerx

Vaccibody

InNexus Biotechnology

Xencor

2.5. Antibody Conjugates

Antibody-Radioisotope Conjugates

Affibody

PBL Therapeutics

Aduro BioTech

Antibody-Drug Conjugates

Medarex

HERMES Biosciences

Celldex Therapeutics

Scancell

Paladin Labs

Antibody-Toxin Conjugates

2.6. Technologies for Improving Monoclonal Antibody

Characteristics

Protein Engineering

Applied Molecular Evolution (Eli Lilly)

Arana Therapeutics

Morphotek

MilleGen/Accuro Biologics

Facet Biotech

Xencor

Merus

Algonomics

f-star

PEGylation

Alternatives to PEGylation

Glycosylation

GlycArt (Roche)

GlycoFi (Merck)

Glycotope

Synageva BioPharma

LFB

Alternative Modes of Administration

Altus Pharmaceuticals

Baxter BioPharma Solutions

Chapter 3

MARKETED AND EMERGING MONOCLONAL

ANTIBODIES: PRESENT AND FUTURE

THERAPEUTICS

3.1. Approved Therapeutic Monoclonal Antibodies

Profiles of Therapeutic Monoclonal Antibodies Approved for

Marketing

Orthoclone OKT3 (Muromonab-CD3) (1986)

ReoPro (Abciximab) (1994)

Rituxan (Rituximab) (1997)

Zenapax (Daclizumab) (1997)

Simulect (Basiliximab) (1998)

Synagis (Palivizumab) (1998)

Remicade (Infliximab) (1998)

Herceptin (Trastuzumab) (1998)

Mylotarg (Gemtuzumab Ozogamicin) (2000)

Campath (Alemtuzumab) (2001)

Zevalin (Ibritumomab Tiuxetan) (2002)

Humira (Adalimumab) (2002)

Xolair (Omalizumab) (2003)

Bexxar (Tositumomab) (2003)

Raptiva (Efalizumab) (2003)

Erbitux (Cetuximab) (2004)

Avastin (Bevacizumab) (2004)

Tysabri (Natalizumab) (2006)

Lucentis (Ranibizumab) (2006)

Vectibix (Panitumumab) (2006)

Soliris (Eculizumab) (2007)

Cimzia (Certolizumab Pegol) (2008)

Ilaris (Canakinumab) (2009)

3.2. Monoclonal Antibodies in Development for Cancer

Unconjugated Monoclonal Antibodies for Cancer

Genmab

Medarex

Biogen Idec

Genentech

Human Genome Sciences

Pfizer

Wilex

Immunomedics

ImClone Systems (Eli Lilly)

Morphotek (Eisai Corp. of North America)

Antisoma

Micromet

UCB

AVEO Pharmaceuticals

Lpath

Northwest Biotherapeutics

Anti-idiotype Monoclonal Antibodies for Cancer

Monoclonal Antibodies: Pipeline Analysis and Competitive Assessment

Menarini Group

Onyvax

Conjugated Monoclonal Antibodies for Cancer

Active Biotech

Antisoma

ImmunoGen

Immunomedics

MedImmune

Seattle Genetics

Merck Serono

Celldex Therapeutics/Curagen

3.3. Monoclonal Antibodies in Development for Immunological

Diseases

Human Genome Sciences

Novartis

UCB

Amgen

Biogen Idec/Genentech

MedImmune

Genmab

Millennium Pharmaceuticals (Takeda Pharmaceutical)

Medarex

NovImmune

BioTie Therapies

Micromet

ZymoGenetics/Novo Nordisk

Glenmark Pharmaceuticals

CSL

LigoCyte Pharmaceuticals

Sanofi-Aventis/Kyowa Hakko Kirin

3.4. Monoclonal Antibodies in Development for Infectious Diseases

Novartis

MedImmune

Human Genome Sciences

Taimed Biologics

Medarex

Elusys Therapeutics

Emergent BioSolutions

Crucell

Progenics Pharmaceuticals

Roche

Genmab

Theraclone Sciences

iBioPharma

3.5. Monoclonal Antibodies in Development for Cardiovascular

Diseases

Ablynx

ThromboGenics/BioInvent International

Affimed Therapeutics

Table of Contents

Lexicon Pharmaceuticals

3.6. Other Therapeutic Antibodies in Development

Amgen

Elan/Wyeth

Eli Lilly

Pfizer

Others

Chapter 4

BUSINESS AND STRATEGIC OUTLOOK: MARKET

POTENTIAL FOR MONOCLONAL ANTIBODIES AND

TRENDS IN THE FIELD

4.1. General Trends

4.2. The Market for Therapeutic Monoclonal Antibodies

Cancer: Solid Tumors

Cancer: Non-Hodgkin’s Lymphoma

Immune and Inflammatory Diseases

Transplant Rejection

Rheumatoid Arthritis

Crohn’s Disease

Psoriasis

Lupus

Multiple Sclerosis

Asthma

Other Emerging Markets

Age-Related Macular Degeneration

HIV

Alzheimer’s Disease

Chapter 5

CHI INSIGHT PHARMA REPORTS MONOCLONAL

ANTIBODIES SURVEY—JULY 2009

References

Company Index with Web Addreses

Monoclonal Antibodies: Pipeline Analysis and Competitive Assessment

Tables

Table 3.1. FDA-Approved Therapeutic Monoclonal Antibodies

Table 3.2. Unconjugated Monoclonal Antibodies in Clinical Trials for Cancer

Table 3.3. Conjugated Monoclonal Antibodies in Clinical Trials for Cancer

Table 3.4. Monoclonal Antibodies in Clinical Trials for Immunological Diseases

Table 3.5. Monoclonal Antibodies in Clinical Trials for Infectious Diseases

Table 3.6. Monoclonal Antibodies in Clinical Trials for Cardiovascular Diseases

Table 3.7. Other Therapeutic Monoclonal Antibodies in Clinical Development

Table 4.1. Worldwide Sales of Therapeutic Monoclonal Antibodies,2007 and 2008

Table 4.2. Estimated New Cancer Cases in United States, Total and Selected Types, 2009

Figures

Figure 1.1. Structure of an Antibody

Figure 2.1. Monoclonal Antibody Production

Figure 2.2. Antibody Engineering

Figure 2.3. Engineered Forms of Antibodies

Figure 1A. Please classify your organization

Figure 2A. Focus of Respondents’ Organizations

Figure 3A. Professional Responsibilities of Respondents

Figure 4A. Changes in mAb Pipelines

Figure 5A. Magnitude of Increase in mAb Pipelines

Figure 6A. Recent Changes in Level of Activity Related to mAbs

Figure 7A. Future Changes in Level of Activity Related to mAbs

Figure 8A. Rate of New mAb Approvals

Figure 9A. Challenges to mAb Development

Figure 10A. Key Technologies

Figure 11A. Future Improvements to mAbs

Figure 12A. Relevant Disease Areas