Abstract
Overview
Introduction
Incidence of primary brain cancer across the seven major markets in 2007 is estimated to be 47,000. Over half of these cases will be glioblastoma multiforme, for which survival prospects are dismal. The median survival for this group of patients is 1.2 years and only 27% of patients are alive after two years. The level of unmet need is therefore high in this disease.
Scope
- Incidence, diagnosis and treatment of primary brain cancer, including treatment regimens by stage and ongoing controversies
- Unmet needs, emerging trends and commercial incentives in primary brain cancer
- Examination of pipeline activity and potential future opportunities for drug developers
- Stakeholder opinions and interview transcripts based on qualitative interviews with six opinion leaders from the US and Europe
Highlights
The standard set by drugs that have been approved for primary brain cancer is low; therefore drugs only need to demonstrate relatively modest improvements in survival to be adopted by physicians. A substantial opportunity also exists for a second-line chemotherapy to enter the primary brain cancer market.
Several molecular markers have been associated with glioma. It is possible that these markers could significantly affect treatment patterns, resulting in a stratified glioma market. Targeted therapies could be reserved solely for patients whose molecular profile indicates that they will benefit from such drugs.
The potential of Phase III pipeline drugs is limited by factors such as low efficacy and complicated delivery methods. Of the drugs in the Phase II pipeline for glioma, targeted therapies show most potential. In particular, angiogenesis inhibitors have considerable commercial potential because they may reduce the co-morbidity edema.
Reasons to Purchase
- Identify the limitations of current therapy available to primary brain cancer patients and the potential of future therapy
- Understand current epidemiological trends in primary brain cancer and ongoing treatment controversies
- Assess the opportunities for innovative targeted therapies in primary brain cancer, particularly in recurrent disease
Table of Contents
- ABOUT DATAMONITOR HEALTHCARE
- About the Oncology pharmaceutical analysis team
- Andrew Paramore - Oncology Lead Analyst & Head of Product Development
- About the Oncology pharmaceutical analysis team
- CHAPTER 1 EXECUTIVE SUMMARY
- Scope of the analysis
- Datamonitor insight into the primary brain cancer market
- Schering-Plough' s Temodar (temozolomide) looks set to maintain its commercial success
- Considerable levels of unmet need and other financial incentives should make the glioma market attractive to drug developers
- The identification of molecular markers may change glioma treatment patterns in the future, by identifying those patients most likely to benefit from specific therapies
- There are very few promising late-phase pipeline drugs for glioma; those that show the most promise are the angiogenesis inhibitors
- Related reports
- Upcoming reports
- CHAPTER 2 PRIMARY BRAIN CANCER: BACKGROUND
- Introduction to primary brain cancer
- Primary brain cancer: a heterogeneous group of tumors
- Classification of primary brain tumors
- WHO primary brain tumor classification system widely used, but could be improved
- Low-grade astrocytoma (WHO grade II)
- High-grade astrocytoma (WHO grade III/IV)
- Oligodendrogliomas
- Prognosis: high-grade glioma patients face dismal survival prospects
- Etiology: prior cranial irradiation is the only established risk factor
- Epidemiology
- Primary CNS tumors account for 1.35% of all cancers and 2.2% of all cancer-related deaths
- Astrocytic and oligodendroglial tumors account for 77% of cases of primary brain cancer; glioblastoma is the most prevalent subtype
- Glioblastoma is most prevalent in patients aged over 60 years
- Incidence rates of primary brain cancer may be increasing; aging population likely to contribute to increased incidence of glioblastoma
- Introduction to primary brain cancer
- CHAPTER 3 CURRENT GLIOMA TREATMENT PRACTICES
- Overview of glioma treatment practices
- Surgery and radiotherapy in glioma treatment
- Surgery has four major purposes in glioma treatment
- Radiotherapy
- Chemotherapy in glioma treatment
- Temodar/Temodal (temozolomide), Schering-Plough
- Gliadel (carmustine polymer wafer), MGI Pharma
- Temodar compares favorably to Gliadel for treatment of newly-diagnosed glioblastoma multiforme
- Nitrosourea and PCV
- Supportive therapy for glioma patients
- Corticosteroids
- Anticonvulsants
- Treatment of newly diagnosed high-grade glioma
- Treatment guidelines recommend daily use of Temodar for glioblastoma patients
- Temodar is firmly established as the standard of care for newly-diagnosed high-grade glioma patients
- Controversy surrounds use of Gliadel
- Treatment of newly diagnosed low-grade glioma
- Guidelines make no firm recommendations on the use of radiotherapy and chemotherapy for low-grade glioma patients
- Low-grade glioma treatment strategies vary from physician to physician; chemotherapy is reserved for patients with progressive symptoms
- Treatment of recurrent glioma
- Guidelines recommend use of chemotherapy for treatment of recurrent high-grade and low-grade glioma
- Temodar replaced by other chemotherapy for recurrent glioma patients
- CHAPTER 4 UNMET NEEDS AND OPPORTUNITIES IN THE GLIOMA MARKET
- Unmet needs in glioma
- Unmet need 1: more effective first-line chemotherapy needed
- Temodar only provides a modest survival benefit
- Well designed Phase II trials needed to ensure potential glioma drugs not overlooked
- Next step forward in first-line therapy may involve multidrug combinations
- Unmet need 2: Blood-brain barrier likely to be an obstacle to drug delivery, particularly for monoclonal antibodies
- Unmet need 3: alternative chemotherapies needed with efficacy equivalent to Temodar for second- and third-line
- Unmet need 4: alternative to corticosteroids for edema treatment needed
- Unmet need 5: need for neuroprotective therapy for a subset of high-grade glioma patients showing prolonged survival
- Unmet need 1: more effective first-line chemotherapy needed
- Molecular markers for glioma - an emerging trend
- Patients with active MGMT promoter gene show a limited survival benefit with Temodar; questions remain over feasibility and reliability of testing
- Ip/19q loss of heterozygosity (LOH) used as diagnostic tool and to help make treatment decisions
- EGFR and PTEN expression may help decide which glioma patients receive EGFR inhibitors
- Incentives to enter the glioma market
- Very few drugs on the market and low bar set by existing therapies
- Uptake of glioma drugs less likely to be limited by same funding constraints as drugs for other cancer types
- Glioma drugs benefit from orphan drug designation and Fast Track status
- Commercial outlook for Temodar
- Unmet needs in glioma
- CHAPTER 5 PIPELINE DRUGS
- Drugs in Phase III trials
- Overview of glioma drugs in Phase III development
- Cotara (131I-chTNT-1/B), Peregrine Pharmaceuticals
- Cotara' s novel mechanism of action may prevent development of drug resistance
- Pivotal product registration trial underway
- Phase II trial results indicate potential efficacy of Cotara
- Datamonitor comment: method of drug delivery and low physician awareness could significantly reduce uptake of Cotara
- CDX-110, Celldex Therapeutics
- CDX-110 is a cancer vaccine targeting EGFRvIII; Phase II/III trial initiated in April 2007
- Datamonitor comment: like other therapeutic cancer vaccines, limited evidence of efficacy shown by CDX-110 to date
- Cerepro (EG-009), Ark Therapeutics
- Cerepro is a gene therapy designed to be used in conjunction with ganciclovir
- Cerepro denied early marketing authorization in Europe on basis of Phase II trial data
- Datamonitor comment: future success of Cerepro hinges on Phase III trial completion
- Gleevec/Glivec (imatinib), Novartis
- Use of Gleevec may be extended to glioma treatment
- Phase II/III clinical trial of Gleevec currently recruiting glioblastoma multiforme patients
- Phase II trial data indicate potential clinical efficacy of Gleevec for treatment of glioma
- Datamonitor comment: despite marketing strength of Novartis, low clinical efficacy may hinder Gleevec' s uptake as a glioma treatment
- TheraCIM (nimotuzumab), YM BioSciences/Center of Molecular
Immunology/Biocon Biopharmaceuticals/Oncoscience
- TheraCIM is a monoclonal antibody targetting the EGFR signal transduction pathway
- Phase III trial of TheraCIM underway for treatment of pontine glioma in children
- Phase II trial data indicate that TheraCIM has a favorable side-effect profile and particular efficacy in pediatric pontine glioma patients
- Datamonitor comment: favorable safety profile could make TheraCIM attractive to physicians, but questions remain over efficacy of EGFR inhibitors in glioma treatment.
- Drugs in Phase II trials
- Overview of glioma drugs in Phase II development: pipeline dominated by targeted therapies
- Genentech/Roche' s Avastin (bevacizumab) and AstraZeneca' s Recentin
(cediranib): anti-angiogenesis drugs show early signs of promise as glioma
therapies
- Phase II trial results indicate that Avastin could potentially find its use extended to treatment of glioma
- Recentin Phase II trial results for recurrent glioblastoma patients show promise
- Datamonitor comment: difficult to say yet whether anti-angiogenesis drugs genuinely reduce size of tumor but reduction of edema could be a significant selling point
- AP-12009, Antisense Pharma
- AP-12009 is an antisense oligonucleotide inhibiting expression of the tumor growth factor TGF-β2
- Phase II studies indicate promising efficacy of AP-12009 in treatment of recurrent or refractory high-grade glioma
- Panzem NCD (2-methoxyestradiol), EntreMed Inc
- Panzem NCD is a formulation of 2-methoxyestradiol with several mechanisms of action
- Phase II data show that Panzem NCD is well-tolerated and potentially shows activity against recurrent glioblastoma multiforme
- EMD-121974 (cilengitide), Merck
- EMD-121974 shows only modest activity against recurrent glioma
- Drugs in Phase III trials
- APPENDIX A
- Bibliography
- List of tables
- List of figures
- About Datamonitor
- About Datamonitor Healthcare
- About the Oncology analysis team
- Disclaimer
- List of Tables
- Table 1: Summary of major types of glioma
- Table 2: WHO classification of glioma subtypes
- Table 3: Glioma patient median survival times by tumor subtype/grade
- Table 4: Estimated incidences of primary brain cancer across the seven major markets, 2002 and 2007
- Table 5: Incidence rates and mean age of incidence of astrocytic and oligodendroglial tumors1
- Table 6: Estimated incidences of glioma by subtype across the seven major markets, 2007
- Table 7: Age distribution of glioblastoma multiforme incidences
- Table 8: Overview of major approvals for Temodar/Temodal in glioma treatment, 1999-2006
- Table 9: Summary of study showing effect of MGMT methylation status on response to Temodar in glioblastoma patients, 2005
- Table 10: Summary of study showing effect of 1p/19q LOH on response to Temodar in anaplastic oligodendroglioma and anaplastic oligoastrocytoma, 2006
- Table 11: Drugs for glioma in Phase III development, May 2007
- Table 12: Drugs for glioma in Phase II development, June 2007
- Table 13: Summary of Phase II data for treatment of recurrent/refractory glioblastoma with AP-12009, 2007
- Table 14: Summary of Phase II data for treatment of recurrent/refractory anaplastic astrocytoma with AP-12009, 2007
- List of Figures
- Figure 1: Estimated proportion of population over 60 years in the seven major markets: 2005, 2010 and 2015
- Figure 2: Summary of Phase III trial of Temodar with radiotherapy compared to radiotherapy alone for newly diagnosed glioblastoma multiforme, 2005
- Figure 3: Summary of Phase III trial comparing Gliadel to polymer placebo, 2003
- Figure 4: Phase II trial results for glioma treatment with Cotara, 2001
- Figure 5: Phase II data: recurrent glioblastoma multiforme treatment with Gleevec, 2004
- Figure 6: Phase II data: recurrent anaplastic astrocytoma/ anaplastic oligodendroglioma treatment with Gleevec, 2006
- Figure 7: Pediatric glioma treatment with TheraCIM (Phase II data), 2006
