MCL1阻害剤の世界市場：臨床試験と商業化の機会（2023年）

MCL-1は、いくつかの癌（主に造血器悪性腫瘍）の病因における中心的なタンパク質として同定されています。MCL-1はダイナミックでユニークなタンパク質であり、細胞周期の進行、代謝、分化など様々な細胞機能に関与しています。しかし、アポトーシスを防ぐBCL-2の生存促進メンバーとしての役割は、癌の有望な治療標的として脚光を浴びています。さらに、MCL-1の過剰発現は、さまざまなシグナル伝達機構を介して、固形癌や血液悪性腫瘍の様々な化学療法剤に対する薬剤耐性をも促進します。したがって、MCL-1は細胞の生存と治療抵抗性を促進する重要な役割を担っていることから、有望な治療標的として浮上し、研究者たちは現在、MCL-1を阻害する戦略の発見に取り組んでいます。

他のタンパク質と比較して、MCL-1の標的阻害にはより多くの利点があります。MCL-1は、乳癌や肺癌を含む多くの癌で過剰発現しており、この2つの癌は罹患率と死亡率が最も高いです。MCL-1は癌細胞のアポトーシス過程を阻害し、生存を促進するため、腫瘍量の増加につながります。前臨床試験において、MCL-1の阻害は細胞死を誘導することが示されました。さらに、MCL-1阻害剤と併用投与された他の抗癌剤の有効性も増加させました。

さらに、MCL-1は現在の治療に対する耐性の発現にも関与していることが指摘されています。特に血液癌では、治療抵抗性は癌患者によく起こる事象であり、治療成績や患者の生存に課題を与えています。MCL-1の過剰発現は、アポトーシスを誘導する薬剤の効果を打ち消してしまうため、このことに一役買っています。MCL-1を標的とすることで、この抵抗性を克服し、造血器癌の治療に用いられる化学療法の効果を高めることができます。さらに、MCL-1阻害剤と他の標的治療薬や抗癌剤を併用することで、癌細胞に対する相乗効果が期待でき、細胞死が促進され治療成績が向上します。

多くの有望な候補化合物の前臨床試験と臨床試験の結果から、有望な結果が得られています。S63845は、前臨床試験を開始した最初の候補の一つであり、現在までに多くの固形癌および造血癌で評価され、有望な結果を示しています。ServierとNovartisは、S63845の臨床試験バージョンであるS64315/MIK665を共同開発しました。前述したように、MCL-1阻害剤は理想的なコンビナトリアル薬剤として機能します。したがって、S64315も造血器癌患者において、化学療法薬であるアザシチジンおよび治験中のBCL-2阻害剤であるVOB560との併用で評価されています。

MCL-1阻害剤の癌治療への使用については、S63845以外にも多数の治験候補化合物の前臨床試験で良好な結果が得られており、説得力があります。また、MCL-1は、固形癌へのこれらの候補薬の展開の結果からも明らかなように、様々な悪性腫瘍の治療標的として使用される可能性があります。MCL-1阻害剤の研究開発はまだ新興の分野であるが、Amgen、Novartis、AstraZenecaなどの著名な製薬会社もこれらの候補化合物の開発に投資しており、MCL-1阻害剤の将来性と今後数年間の予想外の市場成長を裏付けています。MCL-1阻害剤には、MCL-1阻害剤市場の成長可能性を実現するために対処すべき欠点がまだ残っています。

当レポートでは、世界のMCL1阻害剤市場について調査し、市場の概要とともに、MCL1阻害剤の作用機序、癌治療における役割、地域別動向、臨床試験動向、および市場に参入する企業の競合動向などを提供しています。

目次

第1章 調査手法

第2章 MCL1阻害剤のイントロダクション

第3章 MCL1阻害剤- 作用機序

• MCL1の間接的阻害
• MCL1の直接的阻害

第4章 MCL1阻害剤の臨床イノベーション、適応症別

• 白血病
• リンパ腫
• 多発性骨髄腫
• 固形癌
  • 乳癌
  • 肺癌
  • 黒色腫
  • 結腸直腸癌

第5章 世界のMCL1阻害剤市場の機会見通し

• 現在の臨床調査の情勢
• MCL1阻害剤の将来の商業化の機会

第6章 世界のMCL1阻害剤臨床試験の概要

• 会社別
• 国別
• 適応症別
• 患者セグメント別
• 相別

第7章 世界のMCL1阻害剤臨床試験の洞察、企業別、適応症別、相別

• 前臨床
• 第I相
• 第I/II相
• 第II相

第8章 上市済みMCL1阻害剤の臨床的洞察

第9章 競合情勢

• Amgen
• Ascentage Pharma
• Broad Institute
• Captor Therapeutics
• Cyclacel Pharmaceuticals
• Gilead Sciences
• Prelude Therapeutics
• Servier
• Sirnaomics
• Teva Pharmaceutical Industries
• University Of Innsbruck
• Vernalis
• Vichem Chemie

List of Figures

• Figure 4-1: S63845/MIK665 - Phase I Study & Phase I/II Study (NCT04702425 & NCT04629443) Initiation & Completion Year
• Figure 4-2: AMG 176 Phase I Study (NCT05209152) - Initiation & Completion Year
• Figure 4-3: AMG 176 Phase I Study (NCT02675452) - Initiation & Completion Year
• Figure 4-4: MIK665 - Study Initiation & Completion Year
• Figure 4-5: PRT1419 - Study Initiation & Completion Year
• Figure 4-6: AMG 176 Phase I Study (NCT02675452) - Initiation & Completion Year
• Figure 4-7: MIK665 Phase I Study (NCT04702425) - Initiation & Completion Year
• Figure 6-1: Global - MCL1 Inhibitor Drugs Trials by Company (Numbers), 2023
• Figure 6-2: Global - MCL1 Inhibitor Drugs Trials by Country (Numbers), 2023
• Figure 6-3: Global - MCL1 Inhibitor Drugs Trials by Indication (Numbers), 2023
• Figure 6-4: Global - MCL1 Inhibitor Drugs Trials by Patient Segment (Numbers), 2023
• Figure 6-5: Global - MCL1 Inhibitor Drugs Trials by Phase (Numbers), 2023

List of Tables

• Table 4-1: Lymphoma - MCL1 Inhibitors Currently Under Clinical Trials

“Global MCL1 Inhibitor Drug Clinical Trials & Commercialization Opportunity Insights 2023” Report Highlights:

• Research Methodology
• ML1 Inhibitor Drug In Clinical Trials: > 12 Drugs
• Commercially Approved MCL1 Inhibitor Drug: 1 (Synribo)
• ML1 Inhibitor Drug Clinical Trials Insight By Company, Indication & Phase
• Global MCL1 Inhibitor Drug Market Opportunity Outlook
• MCL1 Inhibitor Drug Clinical Innovation & Development Trends By Different Cancers

MCL-1 has been identified as a central protein in the pathogenesis of several cancers, majorly hematopoietic malignancies. It is a dynamic and unique protein, which is involved in a variety of cellular functions, including cell cycle progression, metabolism, and differentiation among others. However, its role as a pro-survival member of the BCL-2 that prevents apoptosis is what has brought it into the limelight as a promising therapeutic target for cancer. In addition, overexpression of MCL-1 also promoted drug resistance of both solid tumors and hematological malignancies to various chemotherapeutic agents through different signaling mechanisms. Therefore, due its key role in promoting cell survival and the resistance to treatment, MCL-1 has emerged as a promising therapeutic target, and researchers are now working to find strategies to inhibit MCL-1.

Compared to other proteins, targeted inhibition of the MCL-1 is has more advantages. The protein is overexpressed in a number of cancers including breast and lung cancers, two cancers having the highest incidence and mortality rates. MCL-1 can prevent the process of apoptosis in cancer cells and promote survival, leading to increase in tumor mass. In preclinical trials, inhibition of the MCL-1 was shown to induce cell death. Additionally, it also increased the efficacy of other anticancer drugs administered in combination with the MCL-1 inhibitor.

Further, MCL-1 is also indicated in the development of resistance to current treatments. Especially in blood cancers, resistance to treatment is a common event occurring in cancer patients, and is something that has been challenging the treatment outcomes and survival of patients. Overexpression of MCL-1 plays a role in this as its upregulation can counteract the effects of drugs that induce apoptosis otherwise. Targeting the MCL-1 can overcome this resistance and enhance the effectiveness of chemotherapies used in treating hematopoietic cancers. Adding on to this, the combination of MCL-1 inhibitors with other targeted therapies and anticancer drugs can have a synergic effect on cancer cells, leading to enhanced cell death and improved treatment outcomes.

Research has also found that while normal cells rely on several survival mechanisms, most cancer cells become highly dependent on MCL-1 for their survival. Therefore, it is hypothesized that targeting the MCL-1 will be a highly targeted strategy specific towards cancer cells, and it will leave non-cancer cells unharmed. To some extent, results from clinical and preclinical trials conducted by researchers and drug developers have been able to justify this. Though there remain some limitations such as the emergence of unforeseen adverse effects such as cardiac problems, the potential of MCL-1 as a therapeutic target cannot be denied, and is an avenue that needs to be explored more with potential candidates.

Results from preclinical and clinical trials for many promising candidates have returned encouraging outcomes. S63845 was among the first candidates to enter preclinical trials, and till date it has been assessed in a number of solid and hematopoietic cancers, and has shown promising results. Servier and Novartis jointly developed S64315/MIK665, the clinical-trial version of S63845. As mentioned above, MCL-1 inhibitors can act as ideal combinatorial agents. Therefore, S64315 too is being assessed in combination with azacitidine, a chemotherapeutic drug, and VOB560, an investigational BCL-2 inhibitor, in patients with hematopoietic cancers.

A compelling case has been made for the use of MCL-1 inhibitors in the treatment of cancer by the positive preclinical trial results of numerous other investigational candidates besides S63845. MCL-1 also has the potential to be used as a therapeutic target for a variety of malignancies, as evidenced by the outcomes of the expansion of these candidates to solid tumors. Research and development of MCL-1 inhibitors is still an emerging field, however, prominent pharmaceutical companies like Amgen, Novartis, and AstraZeneca have also invested in the development of these candidates, which vouches for the future potential of MCL-1 inhibitors and the unanticipated market growth in the coming years. There still remain certain drawbacks associated with MCL-1 inhibitors that need to be addressed to realize the prospective growth potential of the MCL-1 inhibitors market.

Table of Contents

1. Research Methodology

2. Introduction To MCL1 Inhibitors

• 2.1. MCL1 as Therapeutic Target
• 2.2. Role of MCL1 in Cancer

3. MCL1 Inhibitors - Mechanism of Action

• 3.1. Indirect Inhibition of MCL1
• 3.2. Direct Inhibition of MCL1

4. MCL1 Inhibitor Drug Clinical Innovation by Indication

• 4.1. Leukemia
• 4.2. Lymphoma
• 4.3. Multiple Myeloma
• 4.4. Solid Cancers
  • 4.4.1. Breast cancer
  • 4.4.2. Lung Cancer
  • 4.4.3. Melanoma
  • 4.4.4. Colorectal cancer

5. Global MCL1 Inhibitor Drug Market Opportunity Outlook

• 5.1. Current Clinical Research Landscape
• 5.2. MCL1 Inhibitor Drug Future Commercialization Opportunities

6. Global MCL1 Inhibitor Drugs Clinical Trials Overview

• 6.1. By Company
• 6.2. By Country
• 6.3. By Indication
• 6.4. By Patient Segment
• 6.5. By Phase

7. Global MCL1 Inhibitor Drugs Clinical Trials Insight By Company, Indication & Phase

• 7.1. Preclinical
• 7.2. Phase-I
• 7.3. Phase-I/II
• 7.4. Phase-II

8. Marketed MCL1 Inhibitor Drug Clinical Insight

9. Competitive Landscape

• 9.1. Amgen
• 9.2. Ascentage Pharma
• 9.3. Broad Institute
• 9.4. Captor Therapeutics
• 9.5. Cyclacel Pharmaceuticals
• 9.6. Gilead Sciences
• 9.7. Prelude Therapeutics
• 9.8. Servier
• 9.9. Sirnaomics
• 9.10. Teva Pharmaceutical Industries
• 9.11. University Of Innsbruck
• 9.12. Vernalis
• 9.13. Vichem Chemie