Pipeline Insight: Disease Modification in Rheumatoid Arthritis - Competition for the anti-TNF failure patient population increases

Published by: Datamonitor

Published: Apr. 17, 2007 - 222 Pages

Table of Contents

ABOUT DATAMONITOR HEALTHCARE

About the Disease pharmaceutical analysis team

CHAPTER 1 EXECUTIVE SUMMARY

Scope of the analysis

Datamonitor insight into the rheumatoid arthritis market

Key metrics

Datamonitor Pipeline Assessment Summary

CHAPTER 2 PIPELINE OVERVIEW AND DYNAMICS

Pipeline overview

Key companies involved in the rheumatoid arthritis pipeline

Roche and partners

Mutually beneficial partnerships

Key R&D company strategies

Small molecules - is it feasible?

CHAPTER 3 RHEUMATOID ARTHRITIS - MARKET POTENTIAL

Definition of rheumatoid arthritis

Epidemiology of rheumatoid arthritis

Segmentation of rheumatoid arthritis

Mild, moderate and severe patients

Early active rheumatoid arthritis

Anti-TNF failure population

Patient potential for anti-TNF failure drugs

Current market overview

Unmet needs in rheumatoid arthritis

Environmental unmet need

Cost and reimbursement is a barrier to extensive use of some DMARDs

Clinical trial design

Clinical unmet need

Disease modification and side effects are the most important factors to prescribing physicians

Predicting response

CHAPTER 4 R&D APPROACH

Classification of pipeline products

Cytokine T cell targets

Interleukins

TNF inhibitors

Co-stimulatory pathways

Cytokine B cell targets

CD20

Other B-cell mechanisms

Small molecules

MAP kinase

Chemokines

Clinical trial design

Non-responder clinical trials

What is remission?

Clinical trial endpoints in RA

American College of Rheumatology (ACR) measures are the most common endpoints

Disease Activity Scale

Tender Joint Count and Swollen Joint Count

Quality of Life questionnaires

HAQ

Medical Outcome Short Form 36 (SF-36) Health Survey

Disease progression

Total Sharp Score

CHAPTER 5 BIOLOGIC LATE-STAGE DRUG ANALYSIS AND FORECASTS

Overview for the biologic class

Biologic pipeline summary

Comparative forecasts

Definition of current comparator therapy

Orencia (abatacept)

Drug overview

Clinical trial data

More two-year data for abatacept

A rare head-to-head trial with infliximab

Data in JIA

Patient potential

Marketing factors

Satisfaction of unmet needs

Forecasts to 2016

US

EU

Japan

Datamonitor drug assessment summary

Actemra (tocilizumab)

Drug overview

Clinical trial data

Results on three key trials presented at the ACR Annual Meeting 2006

Press release Phase III data

Radiographic progression targeted at ACR

European trial has more realistic results

Tocilizumab in JIA

Patient potential

Marketing factors

Satisfaction of unmet needs

Forecasts to 2016

US

EU

Japan

Datamonitor drug assessment summary

Ocrelizumab (rhuMab 2H7)

Profile

Clinical trial data

The ACTION study results

Patient potential

Marketing potential

Satisfaction of unmet needs

Forecasts to 2016

US

EU

Japan

Datamonitor drug assessment summary

Cimzia (certolizumab)

Drug overview

Clinical trial data

Positive signals but still no fully published data on Cimzia

Phase IIb results

Patient potential

Marketing factors

Satisfaction of unmet needs

Forecasts to 2016

US

EU

Japan

Datamonitor drug assessment summary

Golimumab

Drug overview

Clinical trial data

Patient potential

Smart trial design segments the RA population

Marketing factors

Satisfaction of unmet needs

Forecasts to 2016

US

EU

Japan

Datamonitor drug assessment summary

Atacicept (TACI-Ig)

Drug overview

Clinical trial data

Patient potential

SLE offers a higher unmet need than RA but a difficult route to approval

Marketing factors

Clinical development partnerships boost atacicept's commercial viability

Satisfaction of unmet need

Forecast to 2016

Ofatumumab (HuMax-CD20)

Drug overview

Clinical trials data

Patient potential

NHL as primary indication creates more direct competition with Rituxan/MabThera

Market potential

Genmab's alliances add commercial value

Satisfaction of unmet needs

Forecast to 2016

US

EU

Japan

Datamonitor drug assessment summary

AMG 714 (HuMax Il-15)

Drug overview

Clinical trial data

Patient potential

Marketing factors

Satisfaction of unmet needs

Forecasts to 2016

Other drugs in the biologic DMARD class

TRU-015

Denosumab

Late-stage development compounds recently discontinued

Cell adhesion molecule inhibitors

CHAPTER 6 SMALL MOLECULE LATE-STAGE DRUG ANALYSIS AND FORECASTS

Overview for the small molecules

Small molecule pipeline summary

Definition of current comparator

Careram (iguratimod, T-614)

Drug overview

Clinical trial data

Patient potential

Increased liver enzymes create concern

Lack of disease modifying effects

Market factors

Launch in Japan is more likely than in the US or EU

ACR50 scores lacking in the latest data making clinical efficacy difficult to compare

Satisfaction of unmet needs

Forecasts to 2016

US and EU

Japan

CF101

Drug overview

Clinical trial data

Patient potential

Marketing factors

Satisfaction of unmet need

Forecast to 2016

CP-690550

Overview

Clinical trial data

Patient potential

Marketing factors

Satisfaction of unmet need

Forecast to 2016

US

EU

Japan

Other small molecules

VX-702

AT-001 (dnaJP1)

R-788

ABN-912

RhuDex

Apilimod mesylate (STA-5326)

SCIO-469

MLN-3897

Late-stage development compounds recently discontinued

Apratastat (TMI-005, APS)

MK-0812

CHAPTER 7 INNOVATIVE EARLY-STAGE PROJECTS

Preclinical and discovery compounds

BIBLIOGRAPHY

Webpages

APPENDIX A

Methodology

Datamonitor forecast methodology

IMS Assumptions

Product forecasts

Definition of a standard unit

Datamonitor drug assessment summary

Contributing experts

Report methodology

APPENDIX B

About Datamonitor

About Datamonitor Healthcare

Datamonitor Healthcare's therapy area capabilities

About the Disease analysis team

Disclaimer

List of Tables

Table 1: Prevalence of RA in 2007

Table 2: Products in late-phase development for rheumatoid arthritis, 2007

Table 3: Roche's recently launched and pipeline RA products, 2007

Table 4: Prevalence of rheumatoid arthritis in the seven major markets, 2007

Table 5: RA prevalence applied to growing population rates in the seven major markets, 2006-2016

Table 6: Epidemiology studies into rheumatoid arthritis, 1955-2005

Table 7: Point prevalence of rheumatoid arthritis by age and sex per 100 patients in Norfolk, UK study, 2002

Table 8: CAGR for over-60 population in the seven major markets, 2005-2015

Table 9: Rheumatoid arthritis disease severity as a percentage of total diagnosed RA population in the seven major markets (%), 2006

Table 10: Physician-estimated proportion of patients defined as having early active rheumatoid arthritis in the seven major markets, 2006

Table 11: Estimation of anti-TNF failure patient population in the seven major markets, 2006-2016

Table 12: Interleukin targeting products in the rheumatoid arthritis pipeline, 2007

Table 13: TNF products in the pipeline for rheumatoid arthritis, 2007

Table 14: Approved biologic TNF inhibitors in rheumatoid arthritis across the seven major markets, 2007

Table 15: CD20 targets in human clinical trials for rheumatoid arthritis,, 2007

Table 16: Other B-cell targeting therapies in human clinical trials, 2007

Table 17: Oral p38 MAP kinase targets in clinical trials for rheumatoid arthritis, 2007

Table 18: CCR2 targets in human trials in rheumatoid arthritis, 2007

Table 19: CCR1 targets in human trials for rheumatoid arthritis in the US, 2007

Table 20: Key trial data presented in prescribing information and used for approval of Enbrel and Remicade

Table 21: Key biologic products in the late-stage pipeline for rheumatoid arthritis, 2007

Table 22: Sales forecasts for biologic drugs in rheumatoid arthritis across the seven major markets, 2007-2016

Table 23: Enbrel clinical efficacy, study IV from prescribing information

Table 24: Enbrel: key facts

Table 25: Orencia: prescribing information

Table 26: Published key Phase III abatacept studies, 2007

Table 27: Percentage of ACR responders during the open-label period of the ATTAIN trial in patients who were originally randomized to abatacept (ITT and as-observed analysis)

Table 28: Mean percentage improvement from baseline through 2 years in the ASSURE Trial

Table 29: Abatacept: safety summary

Table 30: Results of abatacept versus infliximab

Table 31: Cost comparison from Abatacept monograph from US Dept of Veterans Affairs, 2006

Table 32: Orencia: satisfaction of unmet needs

Table 33: Percentage of patients in ITT analysis reaching ACR70 when receiving 8mg/kg of tocilizumab or placebo

Table 34: Percentage of patients in ITT analysis reaching DAS28 remission when receiving 8mg/kg of tocilizumab or placebo

Table 35: Actemra preliminary Phase III results

Table 36: Actemra: satisfaction of unmet needs

Table 37: Results of ocrelizumab's Phase I/II ACTION study, at week 24

Table 38: Ocrelizumab: satisfaction of unmet needs

Table 39: Cimzia Phase IIb trial results at week 12, 2001

Table 40: Cimzia: satisfaction of unmet needs

Table 41: ACR20/50/70 and DAS28 assessments at weeks 16 and 52 for all treatment arms

Table 42: Golimumab: satisfaction of unmet needs

Table 43: Atacicept: satisfaction of unmet need

Table 44: Patient baseline demographics for Phase II trial for HuMax-CD20 in rheumatoid arthritis

Table 45: Ofatumumab 24-week clinical response rates per dose group for Phase II trial for HuMax-CD20 in rheumatoid arthritis, % of patients

Table 46: Ofatumumab: satisfaction of unmet needs

Table 47: AMG 714 Phase II ACR20 results at weeks 12, 14 and 16

Table 48: AMG 714: satisfaction of unmet need

Table 49: Forecast sales for small molecule disease modifying agents in development for rheumatoid arthritis across the seven major markets ($m), 2007-2016

Table 50: Small molecule agents in the pipeline for rheumatoid arthritis, 2007

Table 51: Careram: satisfaction of unmet need

Table 52: CF101 satisfaction of unmet need

Table 53: CP-690550: Phase II trial-week 6 responses

Table 55: CP-690550: Phase II trial - numbers withdrawn

Table 54: CP-690550: satisfaction of unmet need

Table 55: Preclinical and discovery RA projects in the seven major markets, 2007

Table 56: ICD10 codes used to define an RA diagnosis

Table 58: Datamonitor drug assessment tool - factors and weightings

List of Figures

Figure 1: Total RA sales and SUs in the seven major markets by region, 2003-06

Figure 2: Datamonitor drug assessment summary for RA 7

Figure 3: Breakdown of rheumatoid arthritis clinical projects by phase, 2007

Figure 4: Rheumatoid arthritis pipeline broken down by mechanism, 2007

Figure 5: Pipeline broken down by administration method and molecule type, 2007

Figure 6: Likely sites of action of the major novel drugs on the RA market, 2007

Figure 7: Percentage of patients on biologics switching or terminating therapy, and key reasons, 2006

Figure 8: Total RA sales and SUs in the seven major markets by region, 2003-06

Figure 9: The top rheumatoid arthritis products/molecules in the seven major markets market, 2005-06

Figure 10: Importance of challenges facing the rheumatoid arthritis market, 2006

Figure 11: Average influence on prescribing decision: weightings assigned by surveyed physicians to key attributes for biologic and traditional DMARDs

Figure 12: Normal and rheumatoid joint comparison

Figure 13: Suggested mechanism for B cell activation in rheumatoid arthritis

Figure 14: Breakdown of small molecules in human clinical trials for RA by mechanism, 2007

Figure 15: Swollen and tender joint count assessment

Figure 16: Datamonitor drug assessment summary of biologic disease modifying drugs in late-stage development for rheumatoid arthritis, 2007-2016

Figure 17: Sales forecasts for biologic drugs in rheumatoid arthritis across the seven major markets, 2007-2016

Figure 18: Orencia's novel mechanism

Figure 19: Bristol-Myers Squibb's strategy for Orencia, February 2007

Figure 20: Orencia's forecast revenues in rheumatoid arthritis across the seven major markets ($m), 2007-2016

Figure 21: Datamonitor drug assessment summary for Orencia in late-stage development for rheumatoid arthritis

Figure 22: Actemra's forecast revenues in rheumatoid arthritis across the seven major markets ($m), 2007-2016

Figure 23: Datamonitor drug assessment summary for Actemra in late-stage development for rheumatoid arthritis

Figure 24: Results of ocrelizumab's Phase I/II ACTION study, at week 24

Figure 25: Ocrelizumab's forecast revenues in rheumatoid arthritis across the seven major markets ($m), 2007-2016

Figure 26: Datamonitor drug assessment summary for Ocrelizumab in late-stage development for rheumatoid arthritis

Figure 27: Cimzia's forecast revenues in rheumatoid arthritis across the seven major markets ($m), 2007-2016

Figure 28: Datamonitor drug assessment summary for Cimzia in late-stage development for rheumatoid arthritis

Figure 29: Golimumab's forecast revenues in rheumatoid arthritis across the seven major markets ($m), 2007-2016

Figure 30: Datamonitor drug assessment summary for golimumab in late-stage development for rheumatoid arthritis

Figure 31: Atacicept: mechanism of action

Figure 32: Ofatumumab's forecast revenues in rheumatoid arthritis across the seven major markets ($m), 2007-2016

Figure 33: Datamonitor drug assessment summary for ofatumumab in late-stage development for rheumatoid arthritis

Figure 34: Datamonitor drug assessment summary of small molecule disease modifying agents in late-stage development for rheumatoid arthritis

Figure 35: Careram's forecast revenues in rheumatoid arthritis in Japan only ($m), 2007-2016

Figure 36: CF101 preliminary Phase IIa results at 12 weeks

Figure 37: CP-690550's forecast revenues in rheumatoid arthritis across the seven major markets ($m), 2007-2016

Abstract

Introduction

The treatment of Rheumatoid Arthritis (RA) has been rapidly evolving over the last decade. The success of the next wave of novel RA therapies depends on their ability to address the key issue of cost effectiveness, as the patient population for anti-TNF's is reaching a maximum and competition moves to anti-TNF failure patients.

Scope

Detailed pipeline analysis for key products in a specific rheumatoid arthritis indication, plus drug sales forecasts to 2016 Overview of patient potential, segmentation by indication and unmet needs in rheumatoid arthritis across the seven major markets Benchmarking of key clinical and company attractiveness of the late-phase pipeline products Comprehensive and up-to-date clinical trial information

Highlights

The anti-TNF failure segment will be an area of increased competition over the next five years, as new products avoid direct confrontation with the established anti-TNF's. This population will increase as more patients use biologics and cycle through the anti-TNF's, but there are a finite number of eligible patients, especially if prices remain high. The race is on between the Roche/Genentech/Biogen Idec and the Genmab/GSK partnerships to launch a CD20-inhibiting monoclonal antibody to follow, and build upon, the success shown by Rituxan/MabThera (rituximab) in the RA indication. At present Roche with ocrelizumab have a slight, but uncertain, advantage. The majority (58%) of projects in human clinical trials are in Phase II development showing the positive growth potential in the RA disease area. However, a large proportion are small molecule, orally available products, which have in the past shown a high attrition rate in Phase II.

Reasons to Purchase

Understand why pricing restraint is necessary for the continued exponential uptake and commercial growth of the biologic DMARDs Quantify the future size and potential of the market for novel treatments in the rheumatoid arthritis indication Use analysis of the common molecular targets under investigation to find gaps in the market for your product

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