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Frontier Pharma: Innovative Licensing Opportunities in Non-Hodgkin Lymphoma

出版商 GBI Research 商品編碼 339964
出版日期 內容資訊 英文 115 Pages
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非何傑金氏淋巴瘤治療藥物的創新授權機會 Frontier Pharma: Innovative Licensing Opportunities in Non-Hodgkin Lymphoma
出版日期: 2015年08月06日 內容資訊: 英文 115 Pages

非何傑金氏淋巴瘤 (NHL) 為達60種的惡性淋巴瘤之總稱,可由形態、細胞遺傳學、免疫表現的特性大致分類為緩慢性及攻擊性。緩慢性NHL可延遲一線治療,但如果是攻擊性NHL,可就不建議延遲。緩慢性NHL與攻擊性NHL皆可在一線化療時,透過結合暢銷抗癌藥物rituxumab獲得高治療反應率,亦可延長緩解持續期間,儘管如此,緩慢性NHL還是無法完全治癒。此外,重複治療導致出現化療抗藥性的案例也不少,成為限制治療選項的因素。現在NHL治療藥物市場上,低分子的化療藥物為主流,為解決這些問題,因應新標的的治療藥物的必要性受到普遍認知,進而使得癌症免疫療法和抑制癌症相關訊息傳導藥物的開發有所進展。


第1章 目次

第2章 報告摘要

  • 標靶療法的開發為NHL治療藥物開發的焦點
  • First-in-Class (創新醫藥品) 不多的NHL治療藥物
  • 無締結契約的大量First-in-Class開發中藥物

第3章 NHL治療藥物開發的創新產品案例

  • 生物製劑的成長機會
  • 分子標的的多樣化
  • 創新First-in-Class產品的開發仍獲得高度關注
  • 法規與保險補助政策的轉變促使First-in-Class產品的開發
  • 持續技術創新
  • 建議

第4章 臨床研究現狀

  • 疾病概要
  • 流行病學與風險因子
  • 症狀
  • 診斷
    • 切片檢查
    • 流式細胞技術與免疫表現型檢查
  • 正常B細胞的開發與NHL的分類
  • 病理生理學
    • BCL2
    • BCL6
    • Wnt/β-catenin訊息傳導路徑
    • BCR訊息傳導路徑
    • PI3K/Akt/mTOR訊息傳導路徑
  • 病患預後

第5章 已上市產品與NHL治療演算法的概要

  • 分子種類別、作用機制別的上市產品
  • 治療演算法
    • NHL的臨床試驗療效標準
    • 緩慢性NHL-濾泡性淋巴瘤
    • 攻擊性NHL
  • 未滿足需求

第6章 開發中藥物產品的評價

  • 開發中藥物產品的開發階段別、分子種類別的比例
  • 開發中藥物產品的作用機制別比例
  • 因應新分子標的的First-in-Class開發計畫

第7章 訊息傳導網路、病因、創新產品的開發

  • 腫瘤的訊息傳導網路的複雜性
  • 訊息傳導路徑、致病突變、First-in-Class分子標的的整合
  • First-in-Class的標的評價

第8章 First-in-Class的標的評價

  • 以脾臟酪氨酸激□為標的的開發中藥物計畫
  • 以PIK3CA與PIK3CB為標的的開發中藥物計畫
  • 以PDPK1為標的的開發中藥物計畫
  • 以EZH2為標的的開發中藥物計畫
  • 以MDM2為標的的開發中藥物計畫
  • 以PTPRC為標的的開發中藥物計畫
  • 以CD40為標的的開發中藥物計畫
  • 以IRAK4為標的的開發中藥物計畫
  • 以CD22為標的的開發中藥物計畫
  • 以BCL6為標的的開發中藥物計畫

第9章 契約與策略整合

  • 全製藥產業的First-in-Class相關契約
  • 授權契約
    • 分子種類別授權契約
  • 共同開發契約
    • 分子種類與作用機制
  • First-in-Class計畫不涉及共同開發契約的授權

第10章 附錄

  • 名詞縮寫
  • 參考文獻
  • 調查方法
  • 二次調查


Product Code: GBIHC367MR

Executive Summary

Non-Hodgkin Lymphoma (NHL) can be seen as a collection of up to 60 smaller subtypes of malignant lymphoid disease, defined by distinct morphological, cytogenetic and immunophenotypic characteristics that can be broadly classified as either indolent or aggressive disease. The slow growing nature of the former means that first-line treatment for diagnosed patients can be delayed, an option not commonly recommended for aggressive disease. Across both indolent and aggressive disease, first-line chemotherapy in combination with the blockbuster drug rituxumab can induce high rates of response, and prolonged durations of remission. Despite this, indolent disease is typically incurable, with the most aggressive lymphoma subtype - diffuse large B-cell lymphoma having 5-year survival rates of ~50%. Re-treatment with chemotherapy can induce second and subsequent remissions, but most NHL patients develop chemotherapy resistant disease, for whom there are limited treatment options. Overall, in terms of numbers small molecule chemotherapeutic agents dominate the current market, with a clear need for novel targeted therapies to prolong durations of remission, and provide options for patients with chemo resistant, heavily pretreated disease.

The current developmental pipeline addresses these gaps in the market, dominated by cancer immunotherapies and inhibitors of cancer-associated signal transduction. Pathways of significant interest include B-cell receptor signaling, the PI3K/Akt/mTOR pathway, and Wnt/ß-catenin signaling, as well as oncogenes such as BCL-6 and BCL-2. Characteristic cell surface molecules that represent targets for cancer immunotherapies include CD19, LMP-1/2 and CD20, with several pipeline drugs already approved for CD20. First-in-class drug development in NHL corresponds strongly to these known somatic mutations and affected pathways. Clinical results of drugs against profiled targets in this report show many are being investigated in relapsed disease.


There are 666 marketed products for NHL, 95% of which are small molecules -

  • What are the dominant mechanisms of action across marketed products?

The treatment of lymphoma is dominated by the use of combination cyclophosphamide based chemotherapy in combination with rituximab -

  • What are these chemotherapy regimens?
  • How did they perform in key clinical trials?

The variation in molecule type has shifted away from small molecules, whose dominance has decreased to 46% across the pipeline -

  • What are the dynamics of the remaining 54% of the pipeline?
  • How does this reflect the need for novel targeted therapies?

There is a significant shift away from cytotoxic agents, with the current pipeline dominated by cancer immunotherapies and signal transduction inhibitors -

  • What is the scientific rationale behind these mechanisms of action?
  • How successful have approved targeted therapies been?

Profiled first-in-class therapies include: PIK3CA, EZH2, CD40 and MDM2 -

  • What is the scientific rationale behind these targets?
  • What preclinical and clinical results are available for drugs against these targets?
  • What is the overall opinion on these targets for drug development across NHL?

Reasons to buy

This report will allow you to -

  • Understand the current clinical and commercial landscape. This includes a comprehensive study of disease pathogenesis, diagnosis, prognosis and the available treatment options available at each stage of diagnosis.
  • Visualize the composition of the NHL market in terms of dominant molecule types and targets, highlighting what the current unmet needs are and how they can be addressed. This knowledge allows a competitive understanding of gaps in the current market.
  • Analyze the NHL pipeline, and stratify by stage of development, molecule type and molecular target. There are promising signs in focussed on the development of targeted therapies for this disease.
  • Visualize the clinical safety and efficacy of drugs against first-in-class targets via a detailed heat map, outlining the results across major clinical trial endpoints.
  • Identify commercial opportunities in the NHL deals landscape by analyzing trends in licensing and co-development deals, and those first-in-class drugs which are yet to be involved in a strategic alliance.

Table of Contents

1. Table of Contents

  • 1.1. List of Tables
  • 1.2. List of Figures

2. Executive Summary

  • 2.1. Development of Targeted Therapies Remains a Focus across NHL Drug Development
  • 2.2. NHL Shows a Moderate Level of First-in-Class Innovation
  • 2.3. High Number of First-in-Class Pipeline Drugs with No Associated Deal

3. The Case for Innovation in NHL Development

  • 3.1. Growing Opportunities for Biological Products
  • 3.2. Diversification of Molecular Targets
  • 3.3. Innovative First-in-Class Product Developments Remain Attractive
  • 3.4. Regulatory and Reimbursement Policy Shifts Favor First-in-Class Product Innovation
  • 3.5. Sustained Innovation
  • 3.6. Report Guidance

4. Clinical Landscape

  • 4.1. Disease Overview
  • 4.2. Epidemiology and Risk Factors
  • 4.3. Symptoms
  • 4.4. Diagnosis
    • 4.4.1. Biopsy
    • 4.4.2. Flow-Cytometry and Immunophenotyping
  • 4.5. Normal B-Cell Development and NHL Classification
  • 4.6. Pathophysiology
    • 4.6.1. BCL2
    • 4.6.2. BCL6
    • 4.6.3. Wnt/β-catenin Pathway
    • 4.6.4. BCR Pathway
    • 4.6.5. PI3K/Akt/mTOR Pathway
  • 4.7. Patient Prognosis

5. Overview of Marketed Products and Treatment Algorithm for NHL

  • 5.1. Marketed Products by Molecule Type and Mechanism of Action
  • 5.2. Treatment Algorithm
    • 5.2.1. Clinical Trial Response Criteria in NHL
    • 5.2.2. Indolent NHL - Follicular Lymphoma
    • 5.2.3. Aggressive NHL
  • 5.3. Unmet Needs

6. Assessment of Pipeline Product Innovation

  • 6.1. Non-Hodgkin Lymphoma Pipeline by Phase and Molecule Type
  • 6.2. Non-Hodgkin Lymphoma Pipeline by Mechanism of Action
  • 6.3. First-in-Class Pipeline Programs Targeting Novel Molecular Targets

7. Signaling Network, Disease Causation and Innovation Alignment

  • 7.1. The Complexity of Signaling Networks in Oncology
  • 7.2. Signaling Pathways, Disease-Causing Mutations and First-in-Class Molecular Target Integration
  • 7.3. First-in-Class Target Matrix Assessment

8. First-in-Class Target Evaluation

  • 8.1. Pipeline Programs Targeting Spleen Tyrosine Kinase
  • 8.2. Pipeline Programs Targeting PIK3CA and PIK3CB
  • 8.3. Pipeline Programs Targeting PDPK1
  • 8.4. Pipeline Programs Targeting EZH2
  • 8.5. Pipeline Programs Targeting MDM2
  • 8.6. Pipeline Programs Targeting PTPRC
  • 8.7. Pipeline Programs Targeting CD40
  • 8.8. Pipeline Programs Targeting IRAK4
  • 8.9. Pipeline Programs Targeting CD22
  • 8.10. Pipeline Programs Targeting BCL6

9. Deals and Strategic Consolidations

  • 9.1. Industry-Wide First-in-Class Deals
  • 9.2. Licensing Deals
    • 9.2.1. Licensing Deals by Molecule Type
  • 9.3. Co-development Deals
    • 9.3.1. Molecule Type and Mechanism of Action
  • 9.4. First-in-Class Programs not Involved in Licensing of Co-development Deals

10. Appendix

  • 10.1. Abbreviations
  • 10.2. Bibliography
  • 10.3. Methodology
  • 10.4. Secondary Research
  • 10.5. Contact Us
  • 10.6. Disclaimer

List of Tables

  • Table 1: WHO Classification of Lymphoid Neoplasms, 2008
  • Table 2: Key Lymphoma Subtypes, Associated Morphological Features, and Cytogenetic and Immunohistochemical Profiles
  • Table 3: Approximate One- and Five-Year Survival Rates of Major NHL Subtypes
  • Table 4: International Working Formulation (IWF) Classification System
  • Table 5: Ann Arbor Staging of Lymphoma and Associated Criteria
  • Table 6: ECOG Performance Status Grade and Criteria
  • Table 7: Follicular Lymphoma International Prognostic Index and International Prognostic Index, Prognostic Risk Criteria for Follicular Lymphomas and All Other Lymphomas Respectively
  • Table 8: Combination Therapies Used in the Treatment of FL, DLBCL and MCL, Part 1
  • Table 9: Combination Therapies Used in the Treatment of FL, DLBCL and MCL, Part 2
  • Table 10: Non-Hodgkin Lymphoma Therapeutics, Clinical Trial Endpoints and Response Criteria
  • Table 11: Clinical Results, R-CHOP21 versus R-CHOP14, 2004
  • Table 12: Effects of Selected Prognostic Factors on the Survival of Patients Treated with R-ICE and R-DHAP for Relapsed DLBCL

List of Figures

  • Figure 1: Innovation Trends in Product Approvals, 1987-2013
  • Figure 2: Sales Performance of First-in-Class and Non-First-in-Class Product Post Marketing Approval
  • Figure 3: Non-Hodgkin Lymphoma, Marketed Products
  • Figure 4: Treatment Algorithm, Follicular Lymphoma
  • Figure 5: Treatment Algorithm, Diffuse Large B-Cell Lymphoma
  • Figure 6: Clinical Trials of Intensive Chemotherapy for Newly Diagnosed Mantle Cell Lymphoma in Eligible Patients
  • Figure 7: Treatment Algorithm, Mantle Cell Lymphoma
  • Figure 8: Pipeline Overview by Stage and Molecule Type
  • Figure 9: Comparative Analysis of Mechanisms of Action between Pipeline and Marketed Products
  • Figure 10: Developmental Pipeline by Mechanism of Action
  • Figure 11: Molecular Target Category Comparison, Pipeline First-in-Class and Established Molecular Targets
  • Figure 12: Non-Hodgkin Lymphoma, Pipeline Drugs Acting Against First-in-Class Targets, Part 1
  • Figure 13: Non-Hodgkin Lymphoma, Pipeline Drugs acting Against First-in-Class Targets, Part 2
  • Figure 14: Non-Hodgkin Lymphoma, Pipeline Drugs Acting Against First-in-Class Targets, Part 3
  • Figure 15: Non-Hodgkin Lymphoma, Pipeline Drugs acting Against First-in-Class Targets, Part 4
  • Figure 16: Non-Hodgkin Lymphoma, Pipeline Drugs acting Against First-in-Class Targets, Part 5
  • Figure 17: Signaling Networks of Functional Families in Non-Hodgkin Lymphoma
  • Figure 18: Location of Key First-in-Class Targets within the Signaling Matrix
  • Figure 19: Target Matrix Assessment (Part 1)
  • Figure 20: Target Matrix Assessment (Part 2)
  • Figure 21: Clinical Trial Results, Drugs Targeting Spleen Tyrosine Kinase
  • Figure 22: Pipeline Programs Targeting Spleen Tyrosine Kinase
  • Figure 23: Clinical Trial Results, Drugs Targeting PIK3CA/PIK3CB
  • Figure 24: Pipeline Programs Targeting PIK3CA/PIK3CB
  • Figure 25: Pipeline Programs Targeting PDPK1
  • Figure 26: Clinical Trial Results, Drugs Targeting EZH2
  • Figure 27: Pipeline Programs Targeting EZH2
  • Figure 28: Clinical Trial Results, Drugs Targeting MDM2
  • Figure 29: Pipeline Programs Targeting MDM2
  • Figure 30: Clinical Trial Results, Drugs Targeting PTPRC
  • Figure 31: Pipeline Programs Targeting PTPRC
  • Figure 32: Clinical Trial Results, Drugs Targeting CD40
  • Figure 33: Clinical Trial Results, Drugs Targeting IRAK4
  • Figure 34: Pipeline Programs Targeting IRAK4
  • Figure 35: Clinical Trial Results, Drugs Targeting CD22
  • Figure 36: Pipeline Programs Targeting CD22
  • Figure 37: Clinical Trial Results, Drugs Targeting BCL6
  • Figure 38: Pipeline Programs Targeting BCL6
  • Figure 39: Industry-Wide Deals by Stage of Development, 2006-2014
  • Figure 40: Industry Licensing Deal Values by Stage of Development, 2006-2014
  • Figure 41: Licensing Deals, Geographic Distribution, 2006-2014
  • Figure 42: Licensing Deals by Year and Value ($), 2006-2014
  • Figure 43: Licensing Deals Analysis by Value, Stage of Development and Molecule Type, 2006-2014
  • Figure 44: Non-Hodgkin Lymphoma, Completed Licensing Deals, 2006-2014
  • Figure 45: Co-development Deals, Geographic Distribution, 2006-2014
  • Figure 46: Co-development Deal Value Analysis, 2006-2014
  • Figure 47: Co-development Deals Analysis by Value, Stage of Development and Molecule Type, 2006-2014
  • Figure 48: Non-Hodgkin Lymphoma Market, Completed Co-development Deals, 2006-2014
  • Figure 49: Non-Hodgkin Market, First-in-Class Programs with no Recorded Prior Deal Involvement, 2006-2014
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