胆道がん（BTC）- 世界市場の考察、疫学、市場予測（2034年）

主なハイライト

• 胆道がん（BTC）は胆道系の上皮性悪性腫瘍で、胆嚢がん（GBC）と胆管がん（CCA）があります。CCAはさらに、肝内CCA、肝周囲CCA（クラツキン腫瘍）、遠位CCAに分けられます。
• BTCの臨床的特徴は腫瘍の位置によります。肝外腫瘍の患者は通常、胆道閉塞による無痛性の黄疸を呈し、肝内腫瘍の患者は通常、疼痛を呈します。一般的な症状には、そう痒症、腹痛、倦怠感、疲労、黄疸、発熱があります。
• 胆道がん（BTC）は通常、画像検査、超音波検査、磁気共鳴画像法（MRI）またはコンピューター断層撮影法（CT）、生検を用いた腹部の臨床検査で診断されます。
• 2023年、BTCの総発生数は日本が主要7市場でもっとも多いです。
• 米国では、BTCは主に70～79歳で発症し、年齢別BTC総症例の約30％を占めます。
• 欧州4ヶ国・英国では、BTCの変異特異的症例はTP53変異が2023年にもっとも多く、KRAS変異がそれに続きました。
• 早期病変に対する治療オプションは、手術、術後補助化学療法です。局所進行例に対しては、局所療法（経動脈的化学塞栓療法（TACE）や外部照射療法（EBRT）など）が考慮されます。局所進行性と転移性の患者に対しては、gemcitabineとcisplatinの併用療法が生存期間を改善することが示されています。
• 主要7市場では、米国が欧州4ヶ国・英国、日本と比較してもっとも高い市場規模を占め、2023年のBTCの48%近い市場シェアを占めました。
• 2023年、欧州4ヶ国・英国の中ではイタリアが最大の市場規模を占め、スペインが最小のシェアを占めました。
• 化学療法レジメンが現在の市場を独占しています。CX-4945やCTX-009など、パイプラインにあるいくつかの新治療法が、予測期間（2024年～2034年）にBTC治療の見通しに前向きな変化をもたらすと予測されています。
• PEMAZYRE（pemigatinib）とLYTGOBI（futibatinib）は、米国食品医薬品局（FDA）から承認された2つのFGFR2阻害薬です。研究者がBTC治療に関連して研究しているもう1つの標的は、免疫チェックポイント分子PD-1です。BTCに関連する最新のFDA承認は、2023年10月にPD-1を阻害する免疫療法であるKEYTRUDA（pembrolizumab）の適応拡大で、局所進行切除不能または転移性BTCの治療にgemcitabineとcisplatinとの併用で使用されることになっています。
• PD-1やFGFR2を標的とする以外にも、米国の研究者らはBTC腫瘍に見られるその他の変異を調べ、より多くの患者に向けた治療オプションを発見しようとしています。TAFINLAR（dabrafenib）+ MEKINIST（trametinib）は、BRAFV600E固形腫瘍の治療薬として承認されています。一方、VITRAKVI（larotrectinib）とROZLYTREK（entrectinib）は、NTRK融合遺伝子陽性の固形腫瘍の治療に使用されています。
• 実データを分析すると、BTCにおける治療パターンと生存転帰が進化していることが明らかになり、異なる治療ライン間でのレジメン使用率のばらつきが浮き彫りになります。治療オプションの進歩にもかかわらず、全体の低い生存率、高い死亡率、高齢や病期などの課題が、治療の意思決定や患者転帰を複雑にしています。

BTC市場の見通し

胆管がんは、胆管内の健康な細胞が変化して制御不能に増殖し、腫瘍と呼ばれる塊を形成することから始まります。腫瘍には良性とがん性があります。良性腫瘍は成長しますが転移はしません。がん性の腫瘍は悪性であり、成長して体の他の部位に転移する可能性があります。

2018年に米国でVITRAKVIという形で最初の承認を受けた後、胆道がんはさまざまな患者セグメントで承認を受けています。特筆すべき近年の進行は、MerckのKEYTRUDAと化学療法の併用（gemcitabine、cisplatin）が2023年11月に米国FDAから承認されたことであり、AstraZenecaのIMFINZIと競合します。KEYTRUDAはIMFINZIと比較して死亡リスクの減少をわずかに示しましたが、どちらも胆道がんの一次治療において改善を示し、IMFINZIは2022年9月にFDA承認を取得しました。

当レポートでは、胆道がん（BTC）の主要7市場（米国、ドイツ、スペイン、イタリア、フランス、英国、日本）について調査分析し、各地域の市場規模、現在の治療法、アンメットニーズ、新薬などの情報を提供しています。

目次

第1章 重要考察

第2章 レポートのイントロダクション

第3章 胆道がん（BTC）のエグゼクティブサマリー

第4章 重要な出来事

第5章 BTC市場の概要

• 主要7市場のBTCの市場シェア分布：治療法別（2020）
• 主要7市場のBTCの市場シェア分布：治療法別（2034）

第6章 疾患の背景と概要

• イントロダクション
• 胆道がん（BTC）の分類
• 病期
• 兆候と症状
• 原因と危険因子
• 病態生理学
• BTCにおける遺伝学的発見
• バイオマーカー
• 胆道がんの診断
• 診断アルゴリズム
• 鑑別診断

第7章 胆道がんの現在の治療法

• 胆道がんの治療

第8章 ガイドライン：診断と治療

• Biliary tract cancer: ESMO Clinical Practice Guideline
• NCCN Guidelines
• EASL-ILCA Clinical Practice Guidelines on the Management of Intrahepatic Cholangiocarcinoma
• Japanese Society of Hepato-Biliary-Pancreatic Surgery（JSHBPS）

第9章 疫学と市場予測の調査手法

第10章 疫学と患者人口

• 主な調査結果
  • 前提条件と根拠
  • 主要7市場のBTCの総発症数
• 米国
• 欧州4ヶ国・英国
• 日本

第11章 ペイシェントジャーニー

第12章 上市済みの治療法

• 主な競合
• PEMAZYRE (pemigatinib): Incyte
• ROZLYTREK (entrectinib): Roche/Genentech
• VITRAKVI (larotrectinib): Bayer/Loxo Oncology
• TIBSOVO (ivosidenib): Agios Pharmaceuticals/Servier Pharmaceuticals
• LYTGOBI (futibatinib): Taiho
• KEYTRUDA (pembrolizumab): Merck
• IMFINZI (durvalumab): AstraZeneca
• TAFINLAR (dabrafenib) + MEKINIST (trametinib): Novartis

第13章 新治療法

• 主な競合
• CTX-009: Compass Therapeutics
• Zanidatamab: Jazz Pharmaceuticals/Zymeworks
• ENHERTU (trastuzumab deruxtecan): AstraZeneca/Daiichi Sankyo
• LENVIMA (lenvatinib): Merck Sharp & Dohme/Eisai
• Silmitasertib (CX-4945): Senhwa Biosciences
• TUKYSA (tucatinib): Seagen/Pfizer
• BOLD-100: Bold Therapeutics
• Tasurgratinib: Eisai
• Tinengotinib: TransThera Sciences
• Rilvegostomig: AstraZeneca/Compugen

第14章 胆道がん（BTC）：市場の分析

• 主な調査結果
  • 主要7市場のBTCの市場規模
• 市場見通し
• 主な市場予測の前提条件
• コンジョイント分析
• 米国の市場規模
• 欧州4ヶ国・英国の市場規模
• 日本の市場規模

第15章 アンメットニーズ

第16章 SWOT分析

第17章 KOLの見解

第18章 市場参入と償還

• 米国
• 欧州4ヶ国・英国
  • ドイツ
  • フランス
  • イタリア
  • スペイン
  • 英国
• 日本

第19章 市場参入と償還：BTC

第20章 付録

第21章 DelveInsightのサービス内容

第22章 免責事項

第23章 DelveInsightについて

List of Tables

• Table 1: Summary of BTC Market and Epidemiology (2020-2034)
• Table 2: TNM and AJCC/UICC Staging Systems for iCCA
• Table 3: AJCC Staging of iCCA: Comparison of Seventh and Eighth Edition
• Table 4: TNM and AJCC/UICC Staging Systems for pCCA
• Table 5: TNM and AJCC/UICC Staging Systems for Perihilar and Distal CCA
• Table 6: TNM and AJCC/UICC Staging Systems for pCCA
• Table 7: TNM and AJCC/UICC Staging Systems for Gall Bladder Cancer
• Table 8: Risk Factors for Biliary Tract Cancer
• Table 9: Host Genetic Polymorphism Associated with Cholangiocarcinoma
• Table 10: Treatment Algorithm of BTC
• Table 11: EASL-ILCA Clinical Practice Guidelines on the Management of Intrahepatic Cholangiocarcinoma
• Table 12: Summary of Clinical Questions and Recommendations: JSHBPS
• Table 13: Total Incident Cases of BTC in the 7MM (2020-2034)
• Table 14: Total Incident Cases of BTC in the United States (2020-2034)
• Table 15: Age-specific Cases of BTC in the United States (2020-2034)
• Table 16: Mutation-specific Cases of BTC in the United States (2020-2034)
• Table 17: Stage-specific Cases of BTC in the United States (2020-2034)
• Table 18: Total Treated Cases of BTC in the United States (2020-2034)
• Table 19: Total Incident Cases of BTC in EU4 and the UK (2020-2034)
• Table 20: Age-specific Cases of BTC in EU4 and the UK (2020-2034)
• Table 21: Mutation-specific Cases of BTC in EU4 and the UK (2020-2034)
• Table 22: Stage-specific Cases of BTC in EU4 and the UK (2020-2034)
• Table 23: Total Treated Cases of BTC in EU4 and the UK (2020-2034)
• Table 24: Total Incident Cases of BTC in Japan (2020-2034)
• Table 25: Age-specific Cases of BTC in Japan (2020-2034)
• Table 26: Mutation-specific Cases of BTC in Japan (2020-2034)
• Table 27: Stage-specific Cases of BTC in Japan (2020-2034)
• Table 28: Total Treated Cases of BTC in Japan (2020-2034)
• Table 29: Comparison of Marketed Drugs
• Table 30: PEMAZYRE, Clinical Trial Description, 2024
• Table 31: VITRAKVI, Clinical Trial Description, 2024
• Table 32: TIBSOVO, Clinical Trial Description, 2024
• Table 33: LYTGOBI, Clinical Trial Description, 2024
• Table 34: KEYTRUDA, Clinical Trial Description, 2024
• Table 35: IMFINZI, Clinical Trial Description, 2024
• Table 36: Comparison of Emerging Drugs Under Development
• Table 37: CTX-009, Clinical Trial Description, 2024
• Table 38: Zanidatamab, Clinical Trial Description, 2024
• Table 39: ENHERTU, Clinical Trial Description, 2024
• Table 40: LENVIMA, Clinical Trial Description, 2024
• Table 41: Silmitasertib, Clinical Trial Description, 2024
• Table 42: TUKYSA, Clinical Trial Description, 2024
• Table 43: BOLD-100, Clinical Trial Description, 2024
• Table 44: Tasurgratinib, Clinical Trial Description, 2024
• Table 45: Tinengotinib, Clinical Trial Description, 2024
• Table 46: Rilvegostomig, Clinical Trial Description, 2024
• Table 47: Total Market Size of BTC in the 7MM, USD million (2020-2034)
• Table 48: Key Market Forecast Assumption of BTC in the United States
• Table 49: Key Market Forecast Assumption of BTC in EU4 and the UK
• Table 50: Key Market Forecast Assumption of BTC in Japan
• Table 51: Total Market Size of BTC in the US, USD million (2020-2034)
• Table 52: Market Size of BTC by Therapies in the US (2020-2034)
• Table 53: Total Market Size of BTC in EU4 and the UK, USD million (2020-2034)
• Table 54: Market Size of BTC by Therapies in EU4 and the UK, USD million (2020-2034)
• Table 55: Total Market Size of BTC in Japan, USD million (2020-2034)
• Table 56: Market Size of BTC by Therapies in Japan, USD million (2020-2034)
• Table 57: NICE Assessment for Biliary Tract Cancer Therapies
• Table 58: IQWiG Assessment for Biliary Tract Cancer Therapies
• Table 59: HAS Assessment for Biliary Tract Cancer Therapies
• Table 60: AEMPS Assessment for Biliary Tract Cancer Therapies
• Table 61: AIFA Assessment for Biliary Tract Cancer Therapies

List of Figures

• Figure 1: Cholangiocarcinoma Subtypes
• Figure 2: Classification of Biliary Tract Cancer
• Figure 3: Clinical Presentations of Biliary Tract Cancer
• Figure 4: Possible Risk Factors and Symptoms
• Figure 5: Risk Factors and Molecular Alterations of BTC
• Figure 6: Cells of Origin in Cholangiocarcinoma (CCA)
• Figure 7: Diagnostic Algorithm for iCCA
• Figure 8: Diagnostic Algorithm for pCCA and dCCA
• Figure 9: Differential Diagnosis of BTC
• Figure 10: Total Incident Cases of BTC in the 7MM (2020-2034)
• Figure 11: Total Incident Cases of BTC in the United States (2020-2034)
• Figure 12: Age-specific Cases of BTC in the United States (2020-2034)
• Figure 13: Mutation-specific Cases of BTC in the United States (2020-2034)
• Figure 14: Stage-specific Cases of BTC in the United States (2020-2034)
• Figure 15: Total Treated Cases of BTC in the United States (2020-2034)
• Figure 16: Total Incident Cases of BTC in EU4 and the UK (2020-2034)
• Figure 17: Age-specific Cases of BTC in EU4 and the UK (2020-2034)
• Figure 18: Mutation-specific Cases of BTC in EU4 and the UK (2020-2034)
• Figure 19: Stage-specific Cases of BTC in EU4 and the UK (2020-2034)
• Figure 20: Total Treated Cases of BTC in EU4 and the UK (2020-2034)
• Figure 21: Total Incident Cases of BTC in Japan (2020-2034)
• Figure 22: Age-specific Cases of BTC in Japan (2020-2034)
• Figure 23: Mutation-specific Cases of BTC in Japan (2020-2034)
• Figure 24: Stage-specific Cases of BTC in Japan (2020-2034)
• Figure 25: Total Treated Cases of BTC in Japan (2020-2034)
• Figure 26: Total Market Size of BTC in the 7MM (2020-2034)
• Figure 27: Total Market Size of BTC in the US (2020-2034)
• Figure 28: Market Size of BTC by Therapies in the US (2020-2034)
• Figure 29: Total Market Size of BTC in EU4 and the UK (2020-2034)
• Figure 30: Market Size of BTC by Therapies in EU4 and the UK (2020-2034)
• Figure 31: Total Market Size of BTC in Japan (2020-2034)
• Figure 32: Market Size of BTC by Therapies in Japan (2020-2034)
• Figure 33: Health Technology Assessment
• Figure 34: Reimbursement Process in Germany
• Figure 35: Reimbursement Process in France
• Figure 36: Reimbursement Process in Italy
• Figure 37: Reimbursement Process in Spain
• Figure 38: Reimbursement Process in the United Kingdom
• Figure 39:Reimbursement Process in Japan

Key Highlights:

• Biliary tract cancers (BTC) constitute epithelial malignancies of the biliary tree and include the following: gallbladder cancer (GBC) and cholangiocarcinoma (CCA). CCA is further divided into intrahepatic CCA, perihilar CCA (Klatskin's tumor), and distal CCA.
• The clinical features of BTC depend on the location of the tumor. Patients with extrahepatic tumors usually present with painless jaundice from biliary obstruction, and patients with intrahepatic tumors usually present with pain. Common complaints include pruritus, abdominal pain, malaise, fatigue, pruritus jaundice, and fever.
• Biliary tract cancer (BTC) is usually diagnosed with the clinical examination of the abdomen, using imaging scans, ultrasound, magnetic resonance imaging (MRI) or computed tomography (CT), and biopsy.
• In 2023, Japan accounted for the highest number of total incident cases of BTC in the 7MM.
• In the United States, BTC occurs majorly in the age group of 70-79 years, constituting approximately ~30% of the total age-specific cases of BTC.
• Among the EU4 and the UK, the mutation-specific cases of BTC were highest in TP53 mutations, followed by KRAS mutations in 2023.
• Treatment options for the early-stage disease include surgery, followed by adjuvant chemotherapy. For patients with locally advanced disease, loco-regional therapies (e.g., trans-arterial chemoembolization [TACE] and external beam radiation therapy [EBRT]) may be considered. For patients with locally advanced and metastatic disease, the combination of gemcitabine and cisplatin has been shown to improve survival.
• In the 7MM, the United States accounted for the highest market size, with nearly 48% of the market share of the BTC market as compared to EU4 and the UK and Japan in 2023.
• In 2023, among EU4 and the UK, Italy accounted for the largest market size, while Spain accounted for the smallest share.
• Chemotherapy regimens dominate the current market. A few emerging therapies in the pipeline, including CX-4945 and CTX-009, are expected to bring a positive shift in the BTC treatment landscape during the forecast period (2024-2034).
• PEMAZYRE (pemigatinib) and LYTGOBI (futibatinib) are two FGFR2 inhibitors that have been approved by the U.S. Food and Drug Administration (FDA). Another target researchers have been studying in relation to BTC treatment is the immune checkpoint molecule PD-1. The most recent FDA approval related to BTC came in October 2023 with an expanded indication for KEYTRUDA (pembrolizumab), an immunotherapy that blocks PD-1, to be used in combination with gemcitabine and cisplatin for the treatment of locally advanced unresectable or metastatic BTC.
• Beyond targeting PD-1 or FGFR2, researchers are looking into other mutations found in BTC tumors as they attempt to discover more treatment options for more patients. TAFINLAR (dabrafenib) + MEKINIST (trametinib) have been approved for use in the United States for the treatment of BRAFV600E solid tumors. Whereas, VITRAKVI (larotrectinib) and ROZLYTREK (entrectinib) are being used for the treatment of NTRK fusion-positive solid tumors.
• Analysis of real-world data reveals evolving treatment patterns and survival outcomes in BTC, highlighting variations in regimen utilization across different lines of therapy. Despite advancements in treatment options, challenges such as low overall survival rates, high mortality rates, and factors like advanced age and disease stage contribute to the complexity of treatment decision-making and patient outcomes.

Report Summary

• The report offers extensive knowledge regarding the epidemiology segments (by region, total incident cases of BTC, age-specific cases, mutation-specific cases, stage-specific cases, and total treated cases) and predictions, presenting a deep understanding of the potential future growth in diagnosis rates, disease progression, and treatment guidelines. It provides comprehensive insights into these aspects, enabling a thorough assessment of the subject matter.
• Additionally, an all-inclusive account of the current management techniques and emerging therapies such as CX-4945 and CTX-009 and the elaborative profiles of late and mid-stage (Phase III and Phase II) and prominent therapies that would impact the current treatment landscape and result in an overall market shift has been provided in the report.
• The report also encompasses a comprehensive analysis of the BTC market, providing an in-depth examination of its historical and projected market size (2020-2034). It also includes the market share of therapies, detailed assumptions, and the underlying rationale for our methodology. The report also includes drug outreach coverage in the 7MM region.
• The report includes qualitative insights that provide an edge while developing business strategies by understanding trends through SWOT analysis and expert insights/KOL views, including experts from various hospitals and prominent universities, patient journey, and treatment preferences that help shape and drive the 7MM BTC market.

Market

Various key players, such as TransThera Sciences, AstraZeneca/ Compugen, Jazz Pharmaceuticals/ Zymeworks and others, are involved in developing therapies for BTC. The expected launch of emerging therapies and other treatments will lead to a significant increase in the market size during the forecast period [2024-2034].

• In 2023, the total market size of BTC was around USD 1000 million, which is expected to increase by 2034 during the study period (2020-2034) in the 7MM.
• Among the 7MM, the United States accounted for the highest market size in 2023, followed by the Japan for BTC.
• During the forecast period (2024-2034), pipeline candidates such as CX-4945 and CTX-009 are expected to drive the rise in BTC market size.
• By 2034, in the US, among all the therapies, the largest market size is expected to be generated by chemotherapy regimens, i.e., USD 360 million.

BTC Drug Chapters

The section dedicated to drugs in the BTC report provides an in-depth evaluation of pipeline drugs (Phase III and Phase II) related to BTC.

The drug chapters section provides valuable information on various aspects related to clinical trials of BTC, such as the pharmacological mechanisms of the drugs involved, designations, approval status, patent information, and a comprehensive analysis of the pros and cons associated with each drug. Furthermore, it presents the most recent news updates and press releases on drugs targeting BTC.

Marketed Therapies

PEMAZYRE (pemigatinib): Incyte

PEMAZYRE is a kinase inhibitor indicated for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test. This indication is approved under accelerated approval based on the overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

PEMAZYRE is a small molecule kinase inhibitor that targets FGFR1, 2, and 3 with IC50 values of less than 2 nM. PEMAZYRE also inhibited FGFR4 in vitro at a concentration approximately 100 times higher than those that inhibit FGFR1, 2, and 3. PEMAZYRE inhibited FGFR1-3 phosphorylation and signaling and decreased cell viability in cancer cell lines by activating FGFR amplifications and fusions that resulted in constitutive activation of FGFR signaling. Constitutive FGFR signaling can support the proliferation and survival of malignant cells. PEMAZYRE exhibited anti-tumor activity in mouse xenograft models of human tumors with FGFR1, 2, or FGFR3 alterations resulting in constitutive FGFR activation, including a patient-derived xenograft model of cholangiocarcinoma that expressed an oncogenic FGFR2-Transformer-2 beta homolog (TRA2b) fusion protein and the KG1 leukemia model that carries a translocation of FGFR1 (FGFR1OP2-FGFR1).

On February 13, 2019, the US FDA granted breakthrough designation (BTD) to PEMAZYRE for the treatment of patients with previously treated advanced/metastatic or unresectable cholangiocarcinoma with an FGFR2 fusion based on the results of an interim analysis of Study INCB 54828-202.

IMFINZI (durvalumab): AstraZeneca

IMFINZI is a programmed death-ligand 1 (PD-L1) blocking antibody indicated in combination with gemcitabine and cisplatin as treatment of adult patients with locally advanced or metastatic BTC.The approval for the treatment of adult patients with locally advanced or metastatic by the US FDA was based on the results from the TOPAZ-1 Phase III trial.

Expression of programmed cell death ligand-1 (PD-L1) can be induced by inflammatory signals (e.g., IFN-gamma) and can be expressed on both tumor cells and tumor-associated immune cells in the tumor microenvironment. PD-L1 blocks T-cell function and activation through interaction with PD-1 and CD80 (B7.1). By binding to its receptors, PD-L1 reduces cytotoxic T-cell activity, proliferation, and cytokine production. Durvalumab is a human immunoglobulin G1 kappa (IgG1?) monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80 (B7.1). Blockade of PD-L1/PD-1 and PD-L1/CD80 interactions releases the inhibition of immune responses without inducing antibody-dependent cell-mediated cytotoxicity (ADCC). PD-L1 blockade with durvalumab led to increased T-cell activation in vitro and decreased tumor size in co-engrafted human tumor and immune cell xenograft mouse models.

In September 2022, AstraZeneca announced that IMFINZI had been approved in the US for the treatment of adult patients with locally advanced or metastatic BTC in combination with chemotherapy (gemcitabine plus cisplatin).

In December 2022, IMFINZI was approved in the European Union (EU) for the first-line treatment of adult patients with unresectable or metastatic BTC in combination with chemotherapy (gemcitabine plus cisplatin).

Note: Detailed assessment will be provided in the final report of BTC.

Emerging Therapies

CTX-009: Compass Therapeutics

CTX-009 is a bispecific antibody that simultaneously blocks Delta-like ligand 4/Notch (DLL4) and vascular endothelial growth factor A (VEGF-A) signaling pathways, which are critical to angiogenesis and tumor vascularization. Preclinical and early clinical data of CTX-009 suggest that blockade of both pathways provides robust antitumor activity across several solid tumors, including colorectal, gastric, cholangiocarcinoma, pancreatic, and non-small cell lung cancer. Partial responses to CTX-009 as monotherapy have been observed in heavily pre-treated patients with cancer who were resistant to currently approved anti-VEGF therapies.

Compass holds the global rights to CTX-009 (also known as ABL001) except for rights in Korea, held by Handok, and rights in China, which were out-licensed to Elpiscience Biopharma.

Currently, CTX-009 is in the Phase III stage of clinical development for the treatment of BTC.

Zanidatamab: Jazz Pharmaceuticals/Zymeworks

Zanidatamab is a novel, late-stage oncology asset with the potential to transform the standard of care in multiple HER2-expressing cancers. It has demonstrated compelling data in biliary tract cancers and gastroesophageal adenocarcinoma with the potential to benefit patients across multiple tumor types.A pivotal Phase II clinical trial evaluating zanidatamab monotherapy in patients with previously treated advanced or metastatic HER2-amplified BTC.

In November 2020, Zymeworks received BTD from the US FDA for zanidatamab in patients with BTC.The US FDA had also granted FTD to zanidatamab as monotherapy for refractory BTC. Zanidatamab had also received ODD from the FDA as well as the European Medicines Agency for the treatment of BTC.

These designations mean zanidatamab is eligible for Accelerated Approval, Priority Review, and Rolling Review, as well as intensive FDA guidance on an efficient drug development program. Zanidatamab has also received Orphan Drug designations from the FDA as well as the European Medicines Agency for the treatment of biliary tract and gastric cancers.

On April 25, 2023, Jazz and Zymeworks entered into a Stock and Asset Purchase Agreement to, among other things, transfer to Jazz certain assets, contracts, and employees associated with the development of zanidatamab.

BTC Market Outlook

Bile duct cancer begins when healthy cells in the bile duct change and grow out of control, forming a mass called a tumor. A tumor can be benign or cancerous. A benign tumor can grow but will not spread. A cancerous tumor is malignant, meaning it can grow and spread to other parts of the body.

Treatment options for the early-stage disease include surgery, followed by adjuvant chemotherapy. For patients with locally advanced and metastatic disease, the combination of gemcitabine and cisplatin has been shown to improve survival.

After receiving initial approval in the United States in 2018 in the form of VITRAKVI, biliary tract cancer has seen approvals for various patient segments. A notable recent development is the approval from the US FDA in November 2023 for Merck's KEYTRUDA in combination with chemotherapy (gemcitabine and cisplatin), presenting competition to AstraZeneca's IMFINZI. While KEYTRUDA showed a slightly lower reduction in the risk of death compared to IMFINZI, both demonstrated improvements in first-line biliary tract cancer, with IMFINZI gaining FDA approval in September 2022.

Apart from this approval, LYTGOBI was approved in September 2022, which gave competition to Incyte's PEMAZYRE, approved in April 2020. To date, other therapies are approved for biliary tract cancer, including ROZLYTREK, TIBSOVO, and the combination of TAFINLAR and MEKINIST.

Key players involved in developing targeted therapies to treat biliary tract cancer include Tinengotinib (TransThera Sciences), Rilvegostomig (AstraZeneca/ Compugen), Zanidatamab (Jazz Pharmaceuticals/ Zymeworks) and others. Some of these have recently entered the late stage of development; DelveInsight's analysts anticipate their launch in the US market to treat BTC.

In a nutshell, potential therapies are being investigated for treating BTC. Even though it is too soon to comment on the above-mentioned promising candidate to enter the market during the forecast period (2024-2034), it is safe to assume that the future of this market is promising. Eventually, the drugs, if approved, shall create a significant difference in the landscape of BTC in the coming years. The treatment space is expected to experience a significant impact in the coming years, owing to the increase in healthcare spending worldwide.

Further details are provided in the report.

BTC Disease Understanding and Treatment

BTC Overview

The biliary tract comprises of gallbladder and intra and extrahepatic biliary tree. Bile is directed through these ducts to the second part of duodenum at major duodenal papilla. The epithelium of the biliary tract is lined with cells called cholangiocytes. Carcinoma of the biliary tract arises from the malignant transformation of the epithelium of the bile ducts which is made up of these cholangiocytes, and is categorized on the basis of its anatomical location as; 1) Intrahepatic cholangiocarcinoma 2) Extrahepatic cholangiocarcinoma, which includes; perihilar tumor also known as Klatskin tumor (originating from the epithelium of the bile duct at the junction of right and left hepatic ducts with the cystic duct where it forms the common bile duct) and distal cholangiocarcinoma outspreading to encompass the gallbladder, ampulla of Vater and pancreatic biliary ducts.

Chronic inflammatory conditions predispose the biliary tract epithelium to modify under stress and undergo transformation that give rise to the cancer of the biliary tract. The most established chronic inflammatory condition associated with biliary tract cancer is primary sclerosing cholangitis (PSC), which is associated with chronic inflammatory bowel disease, particularly ulcerative colitis.

The clinical features of BTC depend on the location of the tumor. Most of the tumors are initiated at the hepatic duct bifurcation, and the rest occur in the distal common bile duct or within the liver. Patients with extrahepatic tumors usually present with painless jaundice from biliary obstruction, and patients with intrahepatic tumors usually present with pain.

Further details are provided in the report.

BTC Diagnosis

The diagnosis of BTC at an early stage remains a significant challenge since, in most cases, patients can remain asymptomatic for a long period during the early stages of BTCs, or symptoms can be unspecified. BTC diagnosis involves abdominal clinical examination, imaging scans (ultrasound, MRI, CT), and biopsy, with staging based on tumor size and metastasis to lymph nodes, liver, lungs, and peritoneum. Late-stage cases often exhibit distant metastasis, guiding treatment decisions.

Further details related to country-based variations are provided in the report.

BTC Treatment

Surgical resection remains the mainstay of cure for BTC. Adjuvant therapy for 6 months with capecitabine is recommended after surgery. For locally advanced and metastatic disease, gemcitabine and cisplatin combination therapy have demonstrated improved survival outcomes.

The role of locoregional therapies, such as transarterial chemoembolization (TACE) and transarterial radioembolization (TARE), has increasingly been investigated for BTC patients. In retrospective studies, TACE with cisplatin has improved survival in unresectable iCCA.

Liver transplantation has been associated with rapid tumor recurrence and low survival and has historically not been recommended as a treatment for unresectable CCA.

Drugs such as entrectinib, larotrectinib, pembrolizumab, dostarlimab-gxly, nivolumab plus ipilimumab, dabrafenib plus trametinib, futibatinib, pemigatinib, ivosidenib, trastuzumab plus pertuzumab, pralsetinib, and selpercatinib, may benefit certain patients with advanced disease harboring specific genomic mutations.

Further details related to treatment and management are provided in the report.

BTC Epidemiology

The BTC epidemiology chapter in the report provides historical as well as forecasted epidemiology segmented by total incident cases, age-specific cases, mutation-specific, stage-specific cases, and total treated cases in the United States, EU4 countries (Germany, France, Italy, Spain) and the United Kingdom, and Japan from 2020 to 2034.

• In 7MM, the United States accounted for the highest number of total incident cases of BTC, which is around 30% of the total incident cases of BTC in the 7MM, in 2023.
• In the US, among the mutation-specific cases of BTC, TP53 cases were highest, followed by KRAS cases in 2023.
• Among the EU4 and the UK, Italy accounted for the highest number of BTC cases, followed by Germany, whereas Spain accounted for the lowest number of BTC cases.
• In 2023, as far as stage-specific cases are concerned, Stage IV accounted for the highest number of cases in Japan. These cases are anticipated to increase by 2034.

KOL Views

To stay abreast of the latest trends in the market, we conduct primary research by seeking the opinions of Key Opinion Leaders (KOLs) and Subject Matter Experts (SMEs) who work in the relevant field. This helps us fill any gaps in data and validate our secondary research.

We have reached out to industry experts to gather insights on various aspects of BTC, including the evolving treatment landscape, patients' reliance on conventional therapies, their acceptance of therapy switching, drug uptake, and challenges related to accessibility. The experts we contacted included medical/scientific writers, professors, and researchers from prestigious universities in the US, Europe, the UK, and Japan.

Our team of analysts at DelveInsight connected with more than 10 KOLs across the 7MM. By obtaining the opinions of these experts, we gained a better understanding of the current and emerging treatment patterns in the BTC market, which will assist our clients in analyzing the overall epidemiology and market scenario.

Some expert opinions have been provided below:

Qualitative Analysis

We perform Qualitative and Market Intelligence analysis using various approaches, such as SWOT analysis and Conjoint Analysis. In the SWOT analysis, strengths, weaknesses, opportunities, and threats in terms of disease diagnosis, patient awareness, patient burden, competitive landscape, cost-effectiveness, and geographical accessibility of therapies are provided. These pointers are based on the Analyst's discretion and assessment of the patient burden, cost analysis, and existing and evolving treatment landscape.

Conjoint analysis analyzes multiple approved and emerging therapies based on relevant attributes such as safety, efficacy, frequency of administration, designation, route of administration, and order of entry. Scoring is given based on these parameters to analyze the effectiveness of therapy. In efficacy, the trial's primary and secondary outcome measures are evaluated. Based on these, the overall efficacy is evaluated.

Further, the therapies' safety is evaluated wherein the acceptability, tolerability, and adverse events are majorly observed, and it sets a clear understanding of the side effects posed by the drug in the trials. In addition, the scoring is also based on the route of administration, order of entry and designation, probability of success, and the addressable patient pool for each therapy. According to these parameters, the final weightage score and the ranking of the emerging therapies are decided.

Market Access and Reimbursement

Because newly authorized drugs are often expensive, some patients escape receiving proper treatment or use off-label, less expensive prescriptions. Reimbursement plays a critical role in how innovative treatments can enter the market. The cost of the medicine, compared to the benefit it provides to patients who are being treated, sometimes determines whether or not it will be reimbursed. Regulatory status, target population size, the setting of treatment, unmet needs, the number of incremental benefit claims, and prices can all affect market access and reimbursement possibilities.

The report further provides detailed insights on the country-wise accessibility and reimbursement scenarios, cost-effectiveness scenario of approved therapies, programs making accessibility easier and out-of-pocket costs more affordable, insights on patients insured under federal or state government prescription drug programs, etc.

BTC Report Insights

• Patient Population
• Therapeutic Approaches
• BTC Market Size and Trends
• Existing Market Opportunity

BTC Report Key Strengths

• Eleven-year Forecast
• The 7MM Coverage
• BTC Epidemiology Segmentation
• Key Cross Competition

BTC Report Assessment

• Current Treatment Practices
• Reimbursements
• Market Attractiveness
• Qualitative Analysis (SWOT, Conjoint Analysis, Unmet needs)

Key Questions:

• Would there be any changes observed in the current treatment approach?
• Will there be any improvements in BTC management recommendations?
• Would research and development advances pave the way for future tests and therapies for BTC?
• Would the diagnostic testing space experience a significant impact and lead to a positive shift in the treatment landscape of BTC?
• What kind of uptake will the new therapies witness in the coming years in BTC patients?

Table of Contents

1. Key Insights

2. Report Introduction

3. Executive Summary of Biliary Tract Cancer (BTC)

4. Key Events

5. BTC Market Overview at a Glance

• 5.1. Market Share by Therapies (%) Distribution of BTC in 2020 in the 7MM
• 5.2. Market Share by Therapies (%) Distribution of BTC in 2034 in the 7MM

6. Disease Background and Overview

• 6.1. Introduction
• 6.2. Classification of Biliary Tract Cancer (BTC)
• 6.3. Staging
  • 6.3.1. Intrahepatic CCA
  • 6.3.2. Perihilar CCA
  • 6.3.3. Distal Extrahepatic CCA
  • 6.3.4. Gall Bladder Cancer
• 6.4. Signs and Symptoms
• 6.5. Causes and Risk Factors
• 6.6. Pathophysiology
• 6.7. Genetic Findings in BTC
• 6.8. Biomarkers
• 6.9. Diagnosis of Biliary Tract Cancer
  • 6.9.1. Diagnosis of iCCA
  • 6.9.2. Diagnosis of pCCA and dCCA
  • 6.9.3. Diagnosis of Gall Bladder Cancer
• 6.1. Diagnostic Algorithm
• 6.11. Differential Diagnosis

7. Current Treatment Practices of Biliary Tract Cancer

• 7.1. Treatment of Biliary Tract Cancer
  • 7.1.1. Treatment Algorithm

8. Guidelines: Diagnosis and Treatment

• 8.1. Biliary tract cancer: ESMO Clinical Practice Guideline
  • 8.1.1. Diagnosis, Pathology, and Molecular Biology
  • 8.1.2. Staging and Risk Assessment
  • 8.1.3. Management of Local and Locoregional Disease
  • 8.1.4. Management of Advanced and Metastatic Disease
    • 8.1.4.1. First-line Treatment
    • 8.1.4.2. Second- and Later-line Treatment
    • 8.1.4.3. Supportive Care
    • 8.1.4.4. Follow-Up, Long-Term Implications and Survivorship
• 8.2. NCCN Guidelines
• 8.3. EASL-ILCA Clinical Practice Guidelines on the Management of Intrahepatic Cholangiocarcinoma
• 8.4. Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS)

9. Epidemiology and Market Forecast Methodology

10. Epidemiology and Patient Population

• 10.1. Key Findings
  • 10.1.1. Assumptions and Rationale
  • 10.1.2. Total Incident Cases of BTC in the 7MM
• 10.2. The United States
  • 10.2.1. Total Incident Cases of BTC in the United States
  • 10.2.2. Age-specific Cases of BTC in the United States
  • 10.2.3. Mutation-specific Cases of BTC in the United States
  • 10.2.4. Stage-specific Cases of BTC in the United States
  • 10.2.5. Total Treated Cases of BTC in the United States
• 10.3. EU4 and the UK
  • 10.3.1. Total Incident Cases of BTC in EU4 and the UK
  • 10.3.2. Age-specific Cases of BTC in EU4 and the UK
  • 10.3.3. Mutation-specific Cases of BTC in EU4 and the UK
  • 10.3.4. Stage-specific Cases of BTC in EU4 and the UK
  • 10.3.5. Total Treated Cases of BTC in EU4 and the UK
• 10.4. Japan
  • 10.4.1. Total Incident Cases of BTC in Japan
  • 10.4.2. Age-specific Cases of BTC in Japan
  • 10.4.3. Mutation-specific Cases of BTC in Japan
  • 10.4.4. Stage-specific Cases of BTC in Japan
  • 10.4.5. Total Treated Cases of BTC in Japan

11. Patient Journey

12. Marketed Therapies

• 12.1. Key Cross Competition
• 12.2. PEMAZYRE (pemigatinib): Incyte
  • 12.2.1. Drug Description
  • 12.2.2. Regulatory Milestones
  • 12.2.3. Other Developmental Activities
  • 12.2.4. Pivotal Clinical Trial
  • 12.2.5. Current Pipeline Activity
    • 12.2.5.1. Clinical Trials Information
  • 12.2.6. Product Profile
• 12.3. ROZLYTREK (entrectinib): Roche/Genentech
  • 12.3.1. Drug Description
  • 12.3.2. Regulatory Milestones
  • 12.3.3. Other Developmental Activities
  • 12.3.4. Pivotal Clinical Trial
  • 12.3.5. Product Profile
• 12.4. VITRAKVI (larotrectinib): Bayer/Loxo Oncology
  • 12.4.1. Product Description
  • 12.4.2. Regulatory Milestones
  • 12.4.3. Other Developmental Activities
  • 12.4.4. Pivotal Clinical Trials
  • 12.4.5. Current Pipeline Activity
    • 12.4.5.1. Clinical Trials Information
  • 12.4.6. Product Profile
• 12.5. TIBSOVO (ivosidenib): Agios Pharmaceuticals/Servier Pharmaceuticals
  • 12.5.1. Product Description
  • 12.5.2. Regulatory Milestones
  • 12.5.3. Other Developmental Activities
  • 12.5.4. Pivotal Clinical Trial
  • 12.5.5. Current Pipeline Activity
    • 12.5.5.1. Clinical Trials Information
  • 12.5.6. Product Profile
• 12.6. LYTGOBI (futibatinib): Taiho
  • 12.6.1. Product Description
  • 12.6.2. Regulatory Milestones
  • 12.6.3. Other Developmental Activities
  • 12.6.4. Pivotal Clinical Trial
  • 12.6.5. Current Pipeline Activity
    • 12.6.5.1. Clinical Trials Information
  • 12.6.6. Product Profile
• 12.7. KEYTRUDA (pembrolizumab): Merck
  • 12.7.1. Product Description
  • 12.7.2. Regulatory Milestones
  • 12.7.3. Other Developmental Activities
  • 12.7.4. Pivotal Clinical Trial
  • 12.7.5. Current Pipeline Activity
    • 12.7.5.1. Clinical Trials Information
  • 12.7.6. Product Profile
• 12.8. IMFINZI (durvalumab): AstraZeneca
  • 12.8.1. Product Description
  • 12.8.2. Regulatory Milestones
  • 12.8.3. Other Developmental Activities
  • 12.8.4. Pivotal Clinical Trial
  • 12.8.5. Current Pipeline Activity
    • 12.8.5.1. Clinical Trials Information
  • 12.8.6. Product Profile
• 12.9. TAFINLAR (dabrafenib) + MEKINIST (trametinib): Novartis
  • 12.9.1. Product Description
  • 12.9.2. Regulatory Milestones
  • 12.9.3. Pivotal Clinical Trial
  • 12.9.4. Product Profile

13. Emerging Therapies

• 13.1. Key Cross Competition
• 13.2. CTX-009: Compass Therapeutics
  • 13.2.1. Drug Description
  • 13.2.2. Other Developmental Activities
  • 13.2.3. Clinical Development
    • 13.2.3.1. Clinical Trials Information
  • 13.2.4. Safety and Efficacy
• 13.3. Zanidatamab: Jazz Pharmaceuticals/Zymeworks
  • 13.3.1. Drug Description
  • 13.3.2. Other Developmental Activities
  • 13.3.3. Clinical Development
    • 13.3.3.1. Clinical Trials Information
  • 13.3.4. Safety and Efficacy
• 13.4. ENHERTU (trastuzumab deruxtecan): AstraZeneca/Daiichi Sankyo
  • 13.4.1. Drug Description
  • 13.4.2. Other Developmental Activities
  • 13.4.3. Clinical Development
    • 13.4.3.1. Clinical Trials Information
  • 13.4.4. Safety and Efficacy
• 13.5. LENVIMA (lenvatinib): Merck Sharp & Dohme/Eisai
  • 13.5.1. Drug Description
  • 13.5.2. Other Developmental Activities
  • 13.5.3. Clinical Development
    • 13.5.3.1. Clinical Trials Information
  • 13.5.4. Safety and Efficacy
• 13.6. Silmitasertib (CX-4945): Senhwa Biosciences
  • 13.6.1. Drug Description
  • 13.6.2. Other Developmental Activities
  • 13.6.3. Clinical Development
    • 13.6.3.1. Clinical Trials Information
  • 13.6.4. Safety and Efficacy
• 13.7. TUKYSA (tucatinib): Seagen/Pfizer
  • 13.7.1. Drug Description
  • 13.7.2. Other Developmental Activities
  • 13.7.3. Clinical Development
    • 13.7.3.1. Clinical Trials Information
  • 13.7.4. Safety and Efficacy
• 13.8. BOLD-100: Bold Therapeutics
  • 13.8.1. Drug Description
  • 13.8.2. Clinical Development
    • 13.8.2.1. Clinical Trials Description
  • 13.8.3. Safety and Efficacy
• 13.9. Tasurgratinib: Eisai
  • 13.9.1. Drug Description
  • 13.9.2. Other Developmental Activities
  • 13.9.3. Clinical Development
    • 13.9.3.1. Clinical Trials Information
  • 13.9.4. Safety and Efficacy
• 13.1. Tinengotinib: TransThera Sciences
  • 13.10.1. Drug Description
  • 13.10.2. Other Developmental Activities
  • 13.10.3. Clinical Development
    • 13.10.3.1. Clinical Trials Information
  • 13.10.4. Safety and Efficacy
• 13.11. Rilvegostomig: AstraZeneca/Compugen
  • 13.11.1. Drug Description
  • 13.11.2. Other Developmental Activities
  • 13.11.3. Clinical Development
    • 13.11.3.1. Clinical Trials Description

14. Biliary Tract Cancer (BTC): Market Analysis

• 14.1. Key Findings
  • 14.1.1. Total Market Size of BTC in the 7MM
• 14.2. Market Outlook
• 14.3. Key Market Forecast Assumptions
• 14.4. Conjoint Analysis
• 14.5. United States Market Size
  • 14.5.1. Total Market Size of BTC in the United States
  • 14.5.2. Market Size of BTC by Therapies in the United States
• 14.6. EU4 and the UK Market Size
  • 14.6.1. Total Market Size of BTC in EU4 and the UK
  • 14.6.2. Market Size of BTC by Therapies in EU4 and the UK
• 14.7. Japan Market Size
  • 14.7.1. Total Market Size of BTC in Japan
  • 14.7.2. Market Size of BTC by Therapies in Japan

15. Unmet Needs

16. SWOT Analysis

17. KOL Views

18. Market Access and Reimbursement

• 18.1. United States
  • 18.1.1. Centre for Medicare and Medicaid Services (CMS)
• 18.2. EU4 and the UK
  • 18.2.1. Germany
  • 18.2.2. France
  • 18.2.3. Italy
  • 18.2.4. Spain
  • 18.2.5. United Kingdom
• 18.3. Japan
  • 18.3.1. MHLW

19. Market Access and Reimbursement: BTC

• 19.1. The National Institute for Health and Care Excellence (NICE): UK
• 19.2. Institute for Quality and Efficiency in Healthcare (IQWiG): Germany
• 19.3. Haute Autorite de Sante (HAS): France
• 19.4. Spanish Agency of Medicines and Medical Products (AEMPS): Spain
• 19.5. Italian Medicines Agency (AIFA): Italy
• 19.6. Patient Access Program

20. Appendix

• 20.1. Bibliography
• 20.2. Report Methodology

21. DelveInsight Capabilities

22. Disclaimer

23. About DelveInsight