Biogenerics 2005: A New Level of Complexity

Published by: Datamonitor

Published: Oct. 28, 2005 - 286 Pages

Table of Contents

Scope

Datamonitor's opinion on the future of the biogenerics market

Biogenerics could be on the market sooner than many might think. The EU regulatory pathway has progressed rapidly over the last two years, and Datamonitor expects the first biogeneric to be approved by 2006. In the US, the situation is less clear, and immediate progress depends on the FDA's use of the controversial 505(b)(2) pathway for insulin and growth hormones. Datamonitor nevertheless expects biogenerics to launch in the US by 2009.

Biogenerics will require an entirely new development and marketing strategy from traditional generics. Companies need to differentiate their biogenerics: marketing and patient support will be much more important, and this will favor companies with strong financial resources and broad commercial experience. Further in the future, the development of 'superbiogenerics', or second-generation versions of biogenerics, will be a vital new growth opportunity.

Different product types will differ greatly in their suitability as targets for biogenerics. Market size and patent expiry are not the only two considerations, as proven by the minimal interest in developing biogeneric insulin. Nevertheless, epoetin, colony stimulating factors and human growth hormone are expected to account for the majority of the $2.2 billion in forecast biogeneric sales by 2010.

Definition of biogenerics

Lack of regulatory pathways for approval is the limiting factor

Why biogenerics are now an issue

Wave of patent expiries makes biogenerics a priority

High cost of biologics increases the importance of biogenerics

Technological advances allow smaller companies to make good biological copies

Market forces: drivers and resistors to biogeneric entry

Key Industry Organizations

GPhA

Biotechnology Industry Organization (BIO)

PhRMA

Commercial factors driving biogeneric approval and uptake

High healthcare costs

Enabling greater patient coverage

Biotech players need to maintain a positive public reputation

Driving innovation

Commercial factors resisting biogeneric approval and uptake

Branded companies' defense of their franchises

Resistance from consumers/physicians to substitution

Gaining public confidence: adequate clinical testing required

Process is the product

Proving equivalence of the protein

Glycosylation

Proving equivalence of the end product

Differences in formulation

Branded view

Scientific argument

Legal and regulatory arguments

Generics view

Scientific argument

Legal and regulatory arguments

Conclusion

How to demonstrate therapeutic equivalence

Analytical techniques

ExSAR: characterizing 3-D protein structure

Momenta and Procognia: analyzing glycosylation patterns

Preclinical and clinical methods

Pricing of biogenerics - low enough to make an impact?

Cost of product development

Clinical data requirements

Manufacturing costs

Cost of marketing

Pricing strategy of biogenerics

Example of typical gross margins achievable

Would this kind of discount change physician prescribing?

Conclusion

EU regulatory overview

Timeline

Key current documents

European Commission: creating a legal framework

2001: EC starts review of pharmaceutical legislation

Directive 2003/63/EC, including Annex I

Directive 2004/27/EC

EMEA: development of a regulatory framework

Overarching guidelines

Comparability guidelines

Quality issues

Non-clinical and clinical issues

Product-specific guidelines

Future developments

Outlook

US regulatory overview

A history of delays...

FDA points to legal obstructions

...but at least some progress is being made

Timeline

Key chronological events

June 2003: Transfer of protein drugs from CBER to CDER

April 2004: Branded opposition intensifies

June 2004: US Senate hearings on follow-on biologics

September 2004: First FDA workshop

February 2005: Second FDA workshop

May 2005: USP monograph ignites debate on comparability

July 2005: FDA guidance is imminent

July 2005: PhRMA members disagree over new legal argument

Future developments

FDA draft guidance

Legal opposition to 505(b)(2)

New legislation from Congress

Likely approval routes

505(b)(2)

Doubts raised by Pfizer's Norvasc victory over Dr. Reddy's

Sandoz's Omnitrope adds to the uncertainty

New legislation enabling FDA guidelines

Outlook

Market opportunity - size of the global biologics markets

Which biologics are suitable targets for biogenerics?

Patent expiries

Market sizes

Comparison of products most at risk from biogenerics

Second wave of biogeneric products

Monoclonal antibodies and fusion proteins

Analysis and forecasts of products likely to face the 'first wave' of biogenerics

EPOs

Overview

Market size and competitors

Second-generation epoetins

Renal failure-induced versus chemotherapy-induced anemias

Patent situation

Suitability for biogenerics

Regulatory situation

Testing requirements for biogeneric epoetins

Biogeneric epoetins marketed or in development

Epoetin market forecast

Conclusion

Insulins

Overview

Market size and competitors

Insulin analogs

Future market development

Patent situation

Suitability for biogenerics

Regulatory situation

Testing requirements for biogeneric insulin

Biogeneric insulin marketed or in development

Insulin market forecast

Conclusion

Human growth hormone

Overview

Market size and competitors

Patent situation

Suitability for biogenerics

Regulatory situation

Sandoz's Omnitrope: landmark negotiations

Testing requirements for biogeneric somatropin

Biogeneric somatropin marketed or in development

Human growth hormone market forecast

Conclusion

Colony stimulating factors (CSFs)

Overview

Market size and competitors

Patent situation

Suitability for biogenerics

Regulatory situation

Testing requirements for biogeneric G-CSF

Biogeneric CSFs marketed or in development

Colony stimulating factor market forecast

Conclusion

Interferon alpha

Overview

Market size and competitors

Future market entrants

Patent situation

Suitability for biogenerics

Regulatory situation

Biogeneric interferon alpha marketed or in development

Interferon alpha market forecast

Conclusion

Interferon beta

Overview

Market size and competitors

Patent situation

Regulatory situation

Suitability for biogenerics

Biogeneric interferon beta marketed or in development

Interferon beta market forecast

Conclusion

Other proteins

Cerezyme (imiglucerase)

Factor VIII

Interferon gamma

Urokinase

Alteplase

Streptokinase

Hepatitis B vaccines

Interleukins

Second-wave biogenerics

Other biologics not immediately amenable to biogenerics

Blood or plasma-derived products and their recombinant alternatives

Other complex biologic products

Vaccines

Antibodies

Heparins: not classified as biogenerics

Forecast sales of biogenerics

Barriers to biogeneric market entry

The key factor is higher development costs for biogenerics

Clinical trials: can (or will) generics companies get involved?

Development costs will primarily discourage late market entrants

Marketing: a new type of generic business model

Biotechnology expertise

Cell lines

Pharmacovigilance monitoring

Regulatory expertise and compliance

Complex patent situation: legal expertise required

Case study: Dynepo

Controlling manufacturing cost

Acquisition/partnership

Outsourcing

Build own facility

Strategies for success: remaining competitive in a dynamic market

Low cost base

Differentiation of biogenerics against competitors

Effective marketing and strong brand reputation

Line extensions, novel formulations

Superbiogenerics - the next level

Superbiogeneric products under development

Neose Technologies: PEGylated interferon alpha and several other partnered projects

BioGeneriX: PEGylated G-CSF and other undisclosed protein

Maxygen: various pegylated interferons, CSF and Factor VII

BioPartners: various slow-release products

Phage Biotechnology: various PEGylated products

Inhaled insulins: Nektar Therapeutics'/Pfizer's Exubera, Aradigm/Novo Nordisk's AERx and MannKind's Technosphere Insulin System

Cangene: long-acting human growth hormone

Dragon Pharmaceutical: slow-release EPO

Biosimilar or "me-too" stand-alone development approach

Key biogenerics companies profiled

Teva (and its subsidiary SICOR)

Overview

Biogeneric product portfolio and pipeline

Partners

Strategy

Outlook

Sandoz

Overview

Biogeneric product portfolio/pipeline

Partners

Strategy

Outlook

BioPartners

Overview

Biogeneric product portfolio/pipeline

Partners

Strategy

Outlook

BioGeneriX (ratiopharm group)

Overview

Biogeneric product portfolio/pipeline

Partners

Strategy

Outlook

Stada (through Bioceuticals)

Overview

Biogeneric product portfolio/pipeline

Partners

Strategy

Outlook

Pliva

Overview

Biogeneric product portfolio/pipeline

Partners

Strategy

Outlook

Cangene

Overview

Biogeneric product portfolio/pipeline

Partners

Strategy

Outlook

GeneMedix

Overview

Financial position

Products

Manufacturing

Technology

Partners

Strategy

Outlook

Phage Biotechnology

Overview

Technology

Biogeneric product portfolio/pipeline

Partners

Strategy

Outlook

Dragon Pharmaceutical

Overview

Biogeneric product portfolio/pipeline

Strategy

Partners

Outlook

Indian biogenerics players

Wockhardt

Biocon

Bharat Biotech

Shantha Biotech

Dr. Reddy's

Chinese biogenerics players

Other biogenerics companies

Barr Pharmaceuticals: Duramed Research

Neose Technologies

Microbix Biosystems

Aceto

CJ Corporation

Strategies to maintain market share

Patent protection

Pegylation

Nektar Therapeutics

Neose Technologies

BiopolyMed

Other pegylation technologies

Limitations of pegylation as a lifecycle management strategy

Novel delivery systems

Pricing strategy

Case studies-companies at risk

Roche

Roferon-A

NeoRecormon

Amgen

Epogen

Neupogen

Johnson & Johnson

Procrit/Eprex

Eli Lilly

Humulin

Humatrope

Novo Nordisk

Novolin

Norditropin

Serono

Serostim/Saizen

Rebif

Biogen Idec

Avonex

Sanofi Aventis

Insuman

Schering-Plough

Intron A

Pfizer

Genotropin

Financial data

Exchange rates

Methodology of sales data collection and forecasting

Forecasting methodology

List of Tables

Table 1: Production systems used for different biological product types

Table 2: Sales of biologics and total pharmaceuticals by 56 leading pharmaceutical companies, 2001-2010

Table 3: Patent expiries of selected key biologic pharmaceuticals

Table 4: Global combined market sizes** for sales of key first-generation biologic product types (assuming no biogenerics), 2003-10

Table 5: Analysis of classes most at risk from biogeneric competition

Table 6: Sales of leading epoetin products worldwide

Table 7: Biogeneric epoetin products

Table 8: Biogeneric epoetin is forecast strong uptake in the five major EU markets between 2006 and 2010

Table 9: Sales of leading human insulin products worldwide

Table 10: Sales of leading insulin analog products worldwide

Table 11: Biogeneric insulin products

Table 12: Biogeneric insulin is expected to have minimal impact on sales of insulin products in the five major EU markets, 2004-10 ($m)

Table 13: Sales of leading somatropin products worldwide

Table 14: Biogeneric somatropin products

Table 15: Biogeneric human growth hormone is expected to capture just under half of the branded market size in the five major EU markets by 2010 ($m)

Table 16: Biogeneric human growth hormone is expected to capture just under half of the branded market size in the five major EU markets by 2010 ($m)

Table 17: Sales of leading CSF products worldwide

Table 18: Biogeneric colony stimulating factors marketed or in development

Table 19: Sales of biogeneric G-CSF are expected to exceed branded G-CSF sales in the five major EU markets by 2010 ($m)

Table 20: Sales of leading interferon alpha products worldwide

Table 21: Biogeneric interferon alpha marketed or in development

Table 22: Sales of biogeneric interferon alpha are expected to almost eradicate branded interferon alpha sales in the five major EU markets by 2010 ($m)

Table 23: Currently marketed interferon beta products

Table 24: Sales of leading interferon beta (IFN beta) products worldwide

Table 25: Key patents covering interferon beta

Table 26: Biogeneric interferon beta marketed or in development

Table 27: Sales of biogeneric interferon beta are expected to have little impact in the five major EU markets by 2010 ($m)

Table 28: Teva's biogeneric product portfolio and pipeline

Table 29: Sandoz' biogeneric product portfolio and pipeline

Table 30: BioPartners' biogeneric product portfolio and pipeline

Table 31: BioGeneriX's biogeneric product portfolio and pipeline

Table 32: Bioceuticals' biogeneric product portfolio and pipeline

Table 33: Pliva's biogeneric product portfolio and pipeline

Table 34: Cangene's biogeneric product portfolio and pipeline

Table 35: GeneMedix's biogeneric product portfolio and pipeline

Table 36: Phage Biotechnology's biogeneric product portfolio and pipeline

Table 37: Dragon Pharmaceutical's biogeneric product portfolio and pipeline

Table 38: Biogeneric products already marketed in India

Table 39: Marketed products from Chinese biogenerics manufacturers

Table 40: Superbiogeneric products developed by Neose Technologies

Table 41: Key products using Nektar Therapeutics' technology

Table 42: Companies with key products at risk from biogenerics

Table 43: Exchange rates*, 2004

List of Figures

Figure 1: Datamonitor expects the initial market leaders to be those with the greatest financial backing and commercial expertise

Figure 2: Global combined market sizes for key first-generation biologic product types (assuming no biogenerics), 2003-10

Figure 3: Comparison of numbers of biogeneric products in development shows that CSFs and epoetin are the two most popular classes

Figure 4: Forecast sales of the six major classes of biogenerics in Western markets, 2005-2010

Figure 5: Timelines of legal and regulatory progress towards a biogeneric approval pathway in the EU

Figure 6: Global sales of biologics and total pharmaceuticals by 56 leading pharmaceutical companies, 2001-2010

Figure 7: Global combined market sizes for key first-generation biologic product types (assuming no biogenerics), 2003-10

Figure 8: Biogeneric epoetin is forecast strong uptake in the five major EU markets between 2006 and 2010

Figure 9: Biogeneric insulin is expected to have minimal impact on sales of insulin products in the five major EU markets, 2004-10 ($m)

Figure 10: Sales of biogeneric G-CSF are expected to exceed branded G-CSF sales in the five major EU markets by 2010 ($m)

Figure 11: Sales of biogeneric interferon alpha are expected to almost eradicate branded interferon alpha sales in the five major EU markets by 2010 ($m)

Figure 12: Sales of biogeneric interferon beta are expected to have little impact in the five major EU markets by 2010 ($m)

Figure 13: Comparison of numbers of biogeneric products in development shows that CSFs and epoetin are the two most popular classes

Figure 14: Forecast sales of the six major classes of biogenerics in Western markets, 2005-2010

Figure 15: Barriers to entry of biogenerics

Figure 16: Datamonitor expects the initial market leaders to be those with the greatest financial backing and commercial expertise

Figure 17: Schering-Plough sharply increased the price of Intron A after the launch of its second-generation Peg-Intron, in order to encourage patient switching

Figure 18: Sales growth of Amgen's G-CSF franchise, 2001-2010

Abstract

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