Market Report Source

Overview

Introduction

The launch of five novel orally administered disease-modifiers is set to revolutionize the multiple sclerosis (MS) market, which will more than double in value across the seven major markets from 2006 to reach $10.7 billion in 2016.

Scope

• Analysis of patient potential, unmet needs and clinical trial design in multiple sclerosis
• Overview of drugs in late- and early-stage clinical development; with analysis of key companies involved in the R&D pipeline
• Detailed profiles of key compounds in development for use in multiple sclerosis, with forecasts of drug revenues to 2016
• Discussion of Biogen Idec’s and Teva’s strategies and insight from key industry opinion leaders

Highlights

There is a significant need for a MS treatment with superior efficacy to current therapies with a less invasive and time-consuming route of administration. Novartis’ oral Fingolimod (FTY720) goes some way to meet these needs and represents the most highly anticipated pipeline drug since the initial launch of Tysabri in 2004. Amid an increasingly competitive first-line therapy market, Datamonitor believes prospective players can gain competitive edge (and healthcare payer acceptance) by defining clear clinical differentiators in their trials. Head-to-head studies with a suitable comparator or showing benefit of add-on therapy represent two possible strategies. Biogen Idec’s Rituxan (rituximab) and BioMS’ MBP-8298 are targeting the prevalent yet largely underserved primary progressive MS (PPMS) and secondary progressive MS (SPMS) indications. Datamonitor predicts that if Rituxan and MBP-8298 launch, then strong uptake can be expected.

Reasons to Purchase

• Understand unmet needs in the multiple sclerosis market based on key opinion leader comments
• Benchmark key late-stage disease-modifying multiple sclerosis compounds against current market leaders
• Assess the global (US, Japan, five major EU) sales forecasts of key late-stage pipeline drugs; and examine their clinical and commercial potential

Table of Contents

ABOUT DATAMONITOR HEALTHCARE

CHAPTER 1 EXECUTIVE SUMMARY

Scope of the analysis

Datamonitor insight into the multiple sclerosis market

Key metrics

Datamonitor Pipeline Assessment Summary

CHAPTER 2 MULTIPLE SCLEROSIS PIPELINE OVERVIEW AND DYNAMICS

Pipeline overview

Oral disease-modifying drugs feature heavily in the late-stage MS pipeline

The majority of products are in development for RRMS

Oral formulations aiming to succeed in a solely injectable market

Key companies involved in the multiple sclerosis pipeline

Current MS players look to offset mass competition with follow-up products

Biogen Idec committed to maintaining MS market leader status

Avonex and Tysabri provide Biogen Idec with leader status in MS market

Rituxan and BG-12 Phase III MS developments lead the way

Early-stage development products add depth to Biogen Idec’s MS pipeline

Biogen Idec’s MS pipeline products are split by class and delivery mechanism

In-licensing and collaborations essential to Biogen Idec’s future MS advancements

Teva looks to supplement its Copaxone franchise

Copaxone represents Teva’s first branded product and now boasts blockbuster status

Oral Copaxone is still many years away from market

Laquinimod replaces oral Copaxone developments as Teva’s front-running oral MS focus

Teva licenses Vaccinex’s VX-15 to strengthen its long-term MS developments

Key R&D company strategies

Combination of oral administration with novel mechanism provides major competitive edge

Targeting SPMS and PPMS can reduce competition but will increase R&D challenge

In-licensing is increasingly important to secure long-term franchise growth

CHAPTER 3 MULTIPLE SCLEROSIS DISEASE OVERVIEW AND MARKET POTENTIAL

Definition of multiple sclerosis

There is no universal course for multiple sclerosis

Segmentation of multiple sclerosis

Researchers have attempted to classify multiple sclerosis according to the clinical course of the disease

Epidemiology of multiple sclerosis

Young female adults are most at risk of developing MS

Genetic and environmental factors appear to play a role in the onset of MS

Over 800,000 individuals in the US, Japan and 5EU markets are estimated to suffer from MS

US

Japan

5EU

The majority of patients suffer from relapse remitting multiple sclerosis

Unmet needs in multiple sclerosis

Prevention and discovery of a cure are the ultimate goals in MS

Unmet need 1: improved efficacy

Improved disease modifying efficacy is the top unmet need in MS

The need for improved symptomatic efficacy remains an issue

Unmet need 2: improved side-effect profile

Improved side-effect profile is in joint second place as the highest unmet need below improved efficacy.

Unmet need 3: approval for a wider range of MS disease severities

Approval for a wider range of MS disease severities is regarded as a high unmet need

Unmet need 4: improved delivery method

The MS market is a solely injectable domain in need of a more less-invasive and user-friendly delivery method

Unmet need 5: fewer drug interactions

The ability to combine treatments depends on the drug-drug interactions

CHAPTER 4 R&D APPROACH

Current treatment options

Current treatment options

There are only six disease-modifying agents currently on the market

Across all stages of MS, 45% of total diagnosed patients do not receive disease-modifying therapy

RRMS and SPMS patients are most likely to recieve disease-modifying therapy

Classification of pipeline products

Novel drug classes look to capitalize in a largely undifferentiated market

Cytokines

Interferons

Interleukin antibodies

Other cytokines

Immunomodulators

Myelin basic protein modulators

Dehydrogenase inhibitors

Human immunoglobulins

Therapeutic vaccines

Others

Clinical trial design in multiple sclerosis

Approved MS disease-modifying drugs set the standard for future trial design

The revised McDonald criteria allows trials to include patients earlier in the course of their disease

Placebo-controlled MS trials might be considered unethical

A placebo control arm is essential in Phase III trials but less of an issue in Phase II trials

The SENTINEL and BEYOND trials provide alternative trial design

Clinical trial endpoints in multiple sclerosis

Relapse rate

Disability/progression measures

Fatigue

Expanded disability status scale

Multiple Sclerosis Functional Composite

Health-related quality-of-life assessments

The Multiple Sclerosis Quality of Life-54 instrument

Multiple Sclerosis Impact Scale

Multiple Sclerosis Symptom and Impact Diary

MRI measures

Conventional MRI techniques to assess lesions

Advanced MRI techniques

Brain atrophy

CHAPTER 5 CYTOKINE LATE-STAGE DRUG ANALYSIS & FORECASTS

Cytokine pipeline Overview

Pipeline summary

Definition of current comparator therapy

MS disease-modifier ‘gold-standard’ is Avonex

Two key studies evaluated the clinical effectiveness of Avonex in MS

Contraindications and adverse reactions reported with the use of Avonex

Avonex’s major competitors and key strengths and weaknesses

Interferon pipeline overview

Pipeline summary

There are two interferon drugs in the late-stage R&D pipeline for MS in 2007

Alferon N injection (interferon alfa-n3)

Drug overview

Clinical trial data

Alferon N under Hemispherx

Retrospective, uncontrolled study

Drug evaluation

Tauferon

Drug overview

Clinical trial data

Pre-clinical and Phase I

Phase II trial initiated

Drug evaluation

Interleukin antibodies pipeline overview

Pipeline summary

There are three interleukin antibodies in the late-stage R&D pipeline for MS in 2007

Daclizumab

Drug overview

Clinical trial data

Phase II open-label clinical studies

Phase II CHOICE study assessing daclizumab added to ongoing interferon-beta treatment

CHOICE study meets primary endpoint

Drug evaluation

CNTO-1275

Drug overview

Clinical trial data

Phase I data show subcutaneous injection of CNT0-1275 is well tolerated

Patient recruitment completed in safety and efficacy Phase II trial

Drug evaluation

ABT-874

Drug overview

Clinical trial data

Drug evaluation

Other cytokines pipeline overview

Pipeline summary

There are four other cytokine drugs in the late-stage R&D pipeline for multiple sclerosis in 2007

Rituxan (rituximab)

Drug overview

Rituxan was first approved for non-Hodgkin’s lymphoma in 1997

Ongoing developments of Rituxan in multiple indications

Clinical trial data

Positive 24-week ‘HERMES’ Phase II RRMS data

Results from Phase II/III PPMS OLYMPUS trial expected in H1-2007

Additional PPMS study in four patients shows Rituxan suppresses B-cells

Patient potential

Marketing potential

Satisfaction of unmet needs

Unmet need 1: improved efficacy

Unmet need 2: improved side-effect profile

Unmet need 3: approval for a wider range of MS severities

Unmet need 4: improved delivery method

Unmet need 5: fewer drug interactions

Forecasts to 2016

Datamonitor drug assessment summary

Campath (alemtuzumab)

Drug overview

Clinical trial data

Early pilot MS studies

Suspension of Phase II RRMS CAMPATH MS 223 trial due to safety concerns

Drug evaluation

ATL-1102 (ISIS-107248)

Drug overview

Clinical trial data

ATL-1102 proved well-tolerated through Phase I studies

Phase II ATL-1102 study in RRMS patients restarts after one-year suspension

Recent animal study supports the use of ATL-1102 in MS

Drug evaluation

MLN1202

Drug overview

Clinical trial data

Results from Phase II trial in 40 RRMS patients set for H1-2007

Drug evaluation

CHAPTER 6 IMMUNOMODULATOR LATE-STAGE DRUG ANALYSIS AND FORECASTS

Comparative forecasts

Comparative Datamonitor drug assessment summaries

Overview

Pipeline summary

There are four key immunomodulator drugs in the late-stage R&D pipeline for multiple sclerosis in 2007

BG-12

Drug overview

Clinical trial data

BG-12 achieves primary endpoint in a 257- patient Phase II RRMS study

Phase III BG-12 MS clinical program includes the DEFINE and CONFIRM international trials that plan to enroll more than 2,000 patients

Patient potential

Marketing potential

Satisfaction of unmet needs

Unmet need 1: improved efficacy

Unmet need 2: improved side-effect profile

Unmet need 3: approval for a wider range of MS severities

Unmet need 4: improved delivery method

Unmet need 5: fewer drug interactions

Forecasts to 2016

Datamonitor drug assessment summary

Laquinimod (SAIK-MS)

Drug overview

Clinical trial data

Phase I dose escalation study meets primary endpoint and identifies 1.2mg as being the maximum-tolerated daily dose.

Phase II trial primary endpoint met with laquinimod 0.3mg/day

77% of patients remained relapse-free during Phase II investigation trial of laquinimod at a higher dose

Teva discusses Phase III Laquinimod clinical program plan with regulatory authorities on back of positive Phase IIb safety and efficacy results

Patient potential

Marketing potential

Satisfaction of unmet needs

Unmet need 1: improved efficacy

Unmet need 2: improved side-effect profile

Unmet need 3: approval for a wider range of MS severities

Unmet need 4: improved delivery method

Unmet need 5: fewer drug interactions

Forecasts to 2016

Datamonitor drug assessment summary

Cpn10 (XToll)

Drug overview

Clinical trial data

Phase I studies demonstrate tolerability of Cpn10 IV infusion and SC injection

Undisclosed Phase IIa trial results meet set objectives

Drug evaluation

GEM-SP

Drug overview

Clinical trial data

Drug evaluation

TV-5010

Drug overview

Drug evaluation

CHAPTER 7 MYELIN BASIC PROTEIN MODULATOR LATE-STAGE DRUG ANALYSIS AND FORECASTS

Overview

Pipeline summary

There are two myelin basic protein modulator drugs in the late-stage R&D pipeline for MS in 2007

MBP-8298

Drug overview

The design of MBP-8298 includes MBP residues 85-96 plus amino acid extension at both ends

MBP-8298 apparently induces immunological tolerance to autoimmune targeting of MBP

The University of Alberta has been granted 88 worldwide patents concerning MBP-8298

Clinical trial data

An in-depth development program of MBP-8298 sees it currently progressing through three MS clinical trials

MBP-8298 showed a reduction of MBP autoantibody in the CSF in chronic progressive MS sufferers during Phase I studies

Positive Phase II chronic progressive MS study results paved the way for Phase III SPMS trials

The MAESTRO-01 & MAESTRO-03 Phase II/III clinical trials in SPMS patients

Commencement of MINDSET-01 Phase II RRMS trial as BioMS aims to advance MBP-8298 into a second indication

Patient potential

Marketing potential

Satisfaction of unmet needs

Unmet need 1: improved efficacy

Unmet need 2: improved side-effect profile

Unmet need 3: approval for a wider range of MS severities

Unmet need 4: improved delivery method

Unmet need 5: fewer drug interactions

Forecasts to 2016

Datamonitor drug assessment summary

BHT-3009

Drug overview

Clinical trial data

Phase I MS trial of BHT-3009 as monotherapy or in combination with atorvastatin