KRAS阻害薬の世界市場：市場規模、対象患者、競合情勢、市場予測：2034年

主なハイライト

• 2023年のKRAS阻害剤市場規模は、主要7ヶ国の中で米国が最も大きく、KRAS阻害剤市場全体の約70%を占めました。
• 米国で承認されたKRAS阻害剤のうち、KRAZATIは調査期間中（2020～2034年）の売上高でルマクラスの優位に立つと予想されます。
• KRAZATIは、2022年12月に発表された最新のNCCNガイドラインにおいて、NSCLC治療のファーストライン以降の治療選択肢として追加されました。
• ルマクラスの売上は、KRAZATIの発売と同時に減少しました。Amgenは、売上高の減少は主にドイツにおける償還契約の一環として実施された価格調整別ものであるとしています。
• 2024年2月、Bristol Myers Squibbは、米国FDAがKRAZATIとセツキシマブとの併用別KRASG12C変異の局所進行性または転移性CRCの治療に関するsNDAを優先審査対象として受理したと発表しました。FDAは2024年6月21日をPDUFA（Prescription Drugs User Fee Act：処方薬ユーザーフィー法）の目標日としました。
• 新興のKRAS企業にとっては、毒性の少ないより安全な組み合わせに重点を移す機会があります。
• 米国は、主要7ヶ国の中でNSCLCのKRAS変異症例数が最も多いです。主要7ヶ国におけるNSCLCのKRAS変異症例の約46％が米国で報告されています。
• G12C阻害剤の同定は、他の一般的なKRAS変異を標的とする新規阻害剤開発への関心を呼び起こしました。がんワクチン、養子細胞療法、PROTACs、CRISPR/Cas9など、G12C阻害剤以外のKRASを標的とする代替戦略を模索する臨床開発の取り組みが進行中です。
• Cardiffオンコロジー（onvansertib）、Gritstone bio（SLATE KRAS）、Hookipa pharma（HB-700）など、Pan-KRAS治療薬の研究開発に携わっている企業は、対応できる対象患者層が広いため、大きな市場ポテンシャルを持つと期待されています。
• 最近、多くの製薬会社がKRAS G12D標的レースに飛び込んできました。MiratiのKRAS G12Dの第I相臨床試験が承認されました。アステラス製薬はKRAS G12Dの新たな候補です。
• 一言で言えば、KRAS阻害剤市場の状況は2024年～2034年の予測期間中に大きく変化すると予測されます。KRAS阻害剤を含む併用療法の可能性は、市場成長の見込みをさらに高める。KRAS阻害剤を他の標的治療、免疫療法、化学療法と併用することで、相乗効果が得られ、治療成績が改善する可能性があります。しかし、すべてのKRAS変異サブタイプを効果的に標的とする阻害剤の開発は依然として課題です。

当レポートは、米国、EU4ヶ国（ドイツ、フランス、イタリア、スペイン）、英国、日本のKRAS阻害剤の市場動向とともに、KRAS阻害剤の歴史的および予測疫学を詳細に理解することができます。

また、現在の治療法、新薬、個々の治療法の市場シェア、2020年から2034年までの主要7ヶ国のKRAS阻害剤市場規模の現状と予測を提供します。また、現在のKRAS阻害剤の治療法/アルゴリズムやアンメットメディカルニーズも網羅し、最良の機会を発掘し、市場の可能性を評価します。

KRASは、RASスーパーファミリーまたはRAS様GTPaseとして知られる低分子GTP結合タンパク質のグループに属します。がん遺伝子であるラット肉腫ウイルス（RAS）はシグナル伝達物質として機能し、正常細胞および悪性細胞における細胞の増殖、分化、生存の制御に重要です。RAS-分裂促進因子活性化プロテインキナーゼ-ERKキナーゼ-細胞外シグナル関連キナーゼ（RAS-RAF-MEK-ERK）経路は、最もよく知られたシグナル伝達経路の一つであり、その異常は一般に様々なタイプのがんの開発に関与しています。KRAS変異は、細胞シグナル伝達経路のタンパク質をコードするKRAS遺伝子の遺伝子変化です。これらの変異は、大腸がん、肺がん、膵臓がんなど、さまざまな種類のがんによくみられます。残念なことに、KRAS変異は歴史的に特異的治療で標的とすることが困難でした。しかし、最近の研究動向により、KRAS変異がんを治療する有望な戦略がいくつか開発されているが、これらの治療法はNSCLCのみに限られています。

一般にKRAS変異がんの治療には、手術、放射線療法、化学療法、標的療法、免疫療法などがあります。ラジオ波焼灼療法（RFA）は、特に手術に耐えられないような、肺の外縁に近い小さな肺腫瘍を持つ一部の人に考慮されるかもしれません。

• 主要7ヶ国のKRAS変異症例総数は、2023年には～49万症例以上となり、予測期間中に増加すると予測されます。
• 選択されたがん種の中で、KRAS変異症例が最も多いのは大腸がん、次いで膵臓がん、NSCLCです。米国では、2023年に約151,000例のKRAS変異型大腸がんが発生しています。
• NSCLCで観察される最も頻度の高いKRAS変異はG12Cです。さらに、CRCと膵臓がんで最も頻度の高いKRAS変異はG12Dです。米国では、KRASG12CはNSCLC症例の37％に認められます。KRASG12Dの割合が最も高いのは膵臓がんで～42％、CRCで～30％です。
• 日本では、KRAS変異の寄与は米国や欧州のような欧米諸国に比べて低いです。

上市済みKRAS阻害薬

LUMAKRAS/LUMYKRAS（ソトラシブ）：Amgen

ルマクラスはRAS GTPaseファミリーの阻害剤で、少なくとも1回の全身療法歴のあるKRAS G12C変異の局所進行性または転移性NSCLC成人患者の治療に適応があります。本剤は2021年5月、少なくとも1回の前治療歴のあるKRAS G12C遺伝子変異を有する局所進行性または転移性NSCLC患者を対象に、FDAが承認した検査により早期承認を取得しました。その後、欧州連合（EU）およびカナダや英国などFDAのProject Orbisイニシアチブの下にある国を含むその他の国でも販売承認が得られました。追加の販売承認申請も現在審査中です。承認は、ソトラシブによる持続的な奏効と良好なベネフィット・リスク・プロファイルを実証する極めて重要なCodeBreaK 100のデータに基づいています。ルマクラスは、欧州連合、英国、スイスにおいてルミクラスとして販売されています。2023年8月、Amgenは米国FDAがルマクラにBTDを付与したと発表しました。

KRAZATI（アダグラシブ）：Mirati Therapeutics

KRAZATIは、FDAが承認した検査によりKRAS G12C遺伝子変異を有する局所進行性または転移性NSCLCで、少なくとも1回の前治療歴のある成人患者を対象とした経口標的治療薬です。KRAZATIはFDAから承認を取得し、2022年12月に米国で市販されました。承認は、多施設単群非盲検臨床試験KRYSTAL-1（NCT03785249）に基づいています。最近、ECは2024年1月、KRAZATIについて、KRASG12C変異進行NSCLCおよび少なくとも1回の前治療歴のある全身療法後の病勢進行の治療に対する条件付き販売承認を与えました。

新たなKRAS阻害薬

JDQ443：Novartis

JDQ443は、構造ベースのドラッグデザインに基づき、2つの類似しないプロトタイプを広範囲に最適化することで得られた、共有結合型のKRAS G12C阻害薬です。JDQ443は、5-メチルピラゾールコアとスピロ-アゼチジンリンカーを含む安定なアトロピソマーで、親電子性のアクリルアミドがKRAS G12Cに最適に結合するように設計されています。JDQ443は、この変異型KRASを構造的に特異的に阻害し、KRAS G12CをGDP結合の不活性状態で捕捉する一方、耐性のルートとして認識されているH95との直接的な相互作用を回避します。現在、この薬剤は、プラチナ製剤ベースの化学療法と免疫チェックポイント阻害剤による治療を順次または併用で受けたことのあるKRAS G12C変異を有する進行NSCLC患者を対象に、JDQ443を単剤療法としてドセタキセルと比較するようデザインされた第III相試験（NCT05132075/KontRASt-02）を実施中です。同社は、第III相単剤療法（2/3L）試験のデータ読み出しとNDA提出を2024年と見込んでいます。

ディバラシブ：Roche/Genentech

Divarasib（GDC-6036/RO7435846）は、経口投与の高活性かつ選択的なKRAS G12C阻害薬です。本薬は、KRAS G12Cオンコプロテインを不可逆的に不活性状態にロックすることにより作用し、腫瘍細胞の増殖を阻止します。非小細胞肺がん、大腸がん、その他のがん種を含む固形がんで研究されています。前臨床モデルでは、KRAS G12C蛋白に対する強力かつ選択的な阻害作用が認められました。GDC-6036は、12位のシステイン残基との特異的な相互作用を通じてKRASG12Cタンパク質のスイッチIIポケットに選択的に結合し、不活性なGDP結合状態に不可逆的にロックするように設計されています。同社によると、2L+NSCLCを対象とした確認的なピボタル第III相試験は2022年第4四半期に開始されました。

KRASは、PDAC、NSCLC、CRCを含む様々ながんにおいて変異しやすいがん遺伝子として知られています。これらの変異は予後不良や高い致死率と関連しています。ドライバー遺伝子の発見と特異的阻害剤の開発により、がん治療のアプローチは大きく変化し、臨床転帰も改善しました。標的療法は無増悪生存期間を延長し、標準的な化学療法よりも低毒性であることが示されています。しかし、数十年にわたる調査にもかかわらず、KRAS（G12C）として知られるKRASの特異的変異型を標的とすることが承認されたソトラシブやアダグラシブのような最近の進歩を除けば、KRAS変異を標的とする有効な戦略は限られています。KRASを直接標的とすることは、KRASの本質的な特徴から、困難な課題でした。その結果、研究者たちは、下流のシグナル伝達分子を標的にしたり、テロメラーゼ阻害剤やRNA干渉のようなエピジェネティックな方法を採用したり、サイクリン依存性キナーゼ阻害剤を含む合成致死戦略を利用するなどの代替アプローチを模索してきました。

2021年5月まで、変異型KRASタンパク質のがん促進作用に対抗する有効な治療法はありません。FDAはこの問題に対処するため、ルマクラス（ソトラシブ）と呼ばれる薬剤に早期承認を与えました。ルマクラスは、局所転移（局所進行性）または遠隔転移（転移性）を起こした非小細胞肺がん（NSCLC）患者を治療するように設計されています。これらの患者は、化学療法などの他の全身がん治療を少なくとも1回受けたことがあり、腫瘍にG12Cとして知られる特異的なKRAS変異を有していなければなりません。

2022年12月、米国FDAはRAS GTPaseファミリー阻害剤であるKRAZATI（アダグラシブ）を、KRAS G12C変異を有する局所進行性または転移性NSCLC成人患者の治療薬として早期承認しました。この承認は、112人の患者を対象としたKRYSTAL-1臨床試験の結果を条件としていました。これらの患者は過去にプラチナ製剤ベースの化学療法と免疫チェックポイント阻害剤による治療を受け、病勢が進行していました。

AmgenとMirati Therapeuticsは、がん治療のためのKRAS阻害剤開発競争の最前線にいます。しかし、両社の現在の候補薬はG12C変異腫瘍のみを標的としており、他のKRAS変異体への対応には大きな隔たりがあります。現在、他の変異型に対して承認された治療法はないため、これはこの分野における大きなアンメット・ニーズです。この課題を認識し、多くの主要な研究者がKRAS変異体を積極的に研究し、NSCLC以外の他のがんにも研究を広げています。この焦点の転換は、より広範なKRAS変異に対応し、複数のがん種を標的とする効果的な治療法の開発に有望な可能性を秘めています。多くの企業が、Cardiff Oncology（onvansertib）、Gritstone bio（SLATE KRAS）、Hookipa Pharma社（HB-700）など、汎KRASでの候補開発に注力しています。

• 主要7ヶ国では、KRAS阻害剤の総市場規模は2023年に約5億米ドルであり、2034年までに大幅に増加すると予想されます。これは主に、主要7ヶ国における罹患率の増加、認知度の向上と治療へのアクセス、がん適応症のための強力なパイプライン活動別もたらされると予想されます。
• 現在、NSCLCの治療の大半はG12C変異型を標的としているため、この変異型は非常に混雑し、競合が激しくなる可能性が高いです。G12C変異型NSCLCに特化した承認薬があるため、NSCLCが市場を独占しています。G12Cの将来的な可能性は、承認されたKRAS治療薬のR/R患者プールや一次治療で見つかるかもしれません。
• 承認された薬剤のうち、KRAZATIは調査期間（2020年～2034年）を通じてルマクラスの市場シェアを上回ると予想されます。
• Amgen社は当初、KRAS阻害薬が最初に承認された企業という栄誉に輝いていました。しかし、アダグラシブに続いてソタラシブも翌年に承認されたため、その地位は短命に終わっています。
• 新興治療薬のうち、主要7ヶ国で最も早く上市されると予想されるKRAS阻害剤は、JDQ443、ディバラシブ（GDC-6036）、オンバンセルチブなどです。
• 新たなKRAS阻害剤治療の中では、SLATE-KRAS/v2+OPDIVOが2034年までに最も高い収益を上げると予想されています。

当レポートでは、世界のKRAS阻害薬市場について調査し、2020～2034年にKRAS阻害薬市場で発売されると予想される潜在的なKRAS阻害薬の取り込み率に焦点を当てています。新たな治療法と薬剤の取り込みに関するさらに詳細な分析は、本レポートに記載されています。

第III相、第II相、第I相段階にあるさまざまな治療薬候補に関する洞察を提供します。また、標的治療薬の開発に携わる主要企業についても分析しています。KRAS阻害剤の新興治療薬に関する共同研究、買収・合併、ライセンシング、特許の詳細に関する情報を網羅しています。

目次

第1章 重要な洞察

第2章 報告書のイントロダクション

第3章 KRAS阻害剤のエグゼクティブサマリー

第4章 主要な出来事

第5章 KRAS阻害剤市場概要

• KRAS阻害剤の市場シェア（％）：治療法別分布、2023年
• KRAS阻害剤の市場シェア（％）：治療法別分布、2034年

第6章 背景と概要

第7章 対象患者

第8章 上市済みKRAS阻害剤

第9章 KRAS阻害剤の新興薬

第10章 KRAS阻害剤市場：主要7ヶ国分析

• 主な調査結果
• KRAS阻害剤市場の見通し
• KRAS阻害剤市場予測の前提条件
• 主要7ヶ国におけるKRAS阻害剤市場規模
  • 主要7ヶ国におけるKRAS阻害剤市場規模（治療法別）
  • 主要7ヶ国におけるKRAS阻害剤市場規模（適応症別）
• 米国：KRAS阻害剤市場
  • 米国におけるKRAS阻害剤市場規模
  • 米国におけるKRAS阻害剤市場規模（治療別）
• EU4ヶ国と英国：KRAS阻害剤市場
  • EU4ヶ国および英国におけるKRAS阻害剤市場規模
  • EU4ヶ国および英国におけるKRAS阻害剤市場規模（治療別）
• 日本：KRAS阻害剤市場
  • 日本におけるKRAS阻害剤市場規模
  • 日本におけるKRAS阻害剤市場規模（治療別）

第11章 KRAS阻害剤のアンメットニーズ

第12章 KRAS阻害剤のSWOT分析

第13章 KRAS阻害剤KOL の見解

第14章 KRAS阻害剤の市場アクセスと償還

• 米国
• EU4ヶ国と英国
• 日本

第15章 付録

第16章 DelveInsightのサービス内容

第17章 免責事項

第18章 DelveInsightについて

List of Tables

• Table 1: Summary of KRAS Mutation Epidemiology (2020-2034)
• Table 2: Sequencing Methods in KRAS Testing
• Table 3: Scope of the Evaluation
• Table 4: Incident cases (2020) and year-over-year (YOY) cancer growth rates
• Table 5: Total Incident Cases of NSCLC in the United States (2020-2034)
• Table 6: KRAS Incident Cases in NSCLC in the United States (2020-2034)
• Table 7: KRAS Variant Cases in NSCLC in the United States (2020-2034)
• Table 8: Total Incident Cases of NSCLC in EU4 and the UK (2020-2034)
• Table 9: KRAS Incident Cases in NSCLC in EU4 and the UK (2020-2034)
• Table 10: KRAS Variant Cases in NSCLC in EU4 and the UK (2020-2034)
• Table 11: Total Incident Cases of NSCLC in Japan (2020-2034)
• Table 12: KRAS Incident Cases in NSCLC in Japan (2020-2034)
• Table 13: KRAS Variant Cases in NSCLC in Japan (2020-2034)
• Table 14: Total Incident Cases of CRC in the United States (2020-2034)
• Table 15: KRAS Incident Cases in CRC in the United States (2020-2034)
• Table 16: KRAS Variant Cases in CRC in the United States (2020-2034)
• Table 17: Total Incident Cases of CRC in EU4 and the UK (2020-2034)
• Table 18: KRAS Incident Cases in CRC in EU4 and the UK (2020-2034)
• Table 19: KRAS Variant Cases in CRC in EU4 and the UK (2020-2034)
• Table 20: Total Incident Cases of CRC in Japan (2020-2034)
• Table 21: KRAS Incident Cases in CRC in Japan (2020-2034)
• Table 22: KRAS Variant Cases in CRC in Japan (2020-2034)
• Table 23: Total Incident Cases of Pancreatic Cancer in the United States (2020-2034)
• Table 24: KRAS Incident Cases in Pancreatic Cancer in the United States (2020-2034)
• Table 25: KRAS Variant Cases in Pancreatic Cancer in the United States (2020-2034)
• Table 26: Total Incident Cases of Pancreatic Cancer in EU4 and the UK (2020-2034)
• Table 27: KRAS Incident Cases in Pancreatic Cancer in EU4 and the UK (2020-2034)
• Table 28: KRAS Variant Cases in Pancreatic Cancer in EU4 and the UK (2020-2034)
• Table 29: Total Incident Cases of Pancreatic Cancer in Japan (2020-2034)
• Table 30: KRAS Incident Cases in Pancreatic Cancer in Japan (2020-2034)
• Table 31: KRAS Variant Cases in Pancreatic Cancer in Japan (2020-2034)
• Table 32: Comparison of Marketed Drugs
• Table 33: LUMAKRAS/LUMYKRAS, Clinical Trial Description, 2024
• Table 34: KRAZATI, Clinical Trial Description, 2024
• Table 35: Comparison of Emerging drugs
• Table 36: JDQ443, Clinical Trial Description, 2024
• Table 37: Divarasib, Clinical Trial Description, 2024
• Table 38: Avutometinib (VS-6766), Clinical Trial Description, 2024
• Table 39: RMC-4630, Clinical Trial Description, 2024
• Table 40: Onvansertib, Clinical Trial Description, 2024
• Table 41: IMM-1-104, Clinical Trial Description, 2024
• Table 42: Glecirasib (JAB-21822), Clinical Trial Description, 2024
• Table 43: BBP-398, Clinical Trial Description, 2024
• Table 44: MRTX1133, Clinical Trial Description, 2024
• Table 45: DCC-3116, Clinical Trial Description, 2024
• Table 46: ELI-002, Clinical Trial Description, 2024
• Table 47: D-1553, Clinical Trial Description, 2024
• Table 48: SLATE-KRAS, Clinical Trial Description, 2024
• Table 49: D3S-001, Clinical Trial Description, 2024
• Table 50: Key Market Forecast Assumption of KRAS Inhibitors in the US
• Table 51: Key Market Forecast Assumption of KRAS Inhibitors in EU4 and the UK
• Table 52: Key Market Forecast Assumption of KRAS Inhibitors in Japan
• Table 53: Total KRAS Inhibitor Market Size in the 7MM, in USD million (2020-2034)
• Table 54: KRAS Inhibitor Market Size by Therapies in the 7MM, in USD million (2020-2034)
• Table 55: Total KRAS Inhibitor Market Size inhibitors in the United States, in USD million (2020-2034)
• Table 56: KRAS Inhibitor Market Size by Therapies in the United States, in USD million (2020-2034)
• Table 57: Total KRAS Inhibitor Market Size in EU4 and the UK, in USD million (2020-2034)
• Table 58: KRAS Inhibitor Market Size by Therapies in Germany, in USD million (2020-2034)
• Table 59: KRAS Inhibitor Market Size by Therapies in France, in USD million (2020-2034)
• Table 60: KRAS Inhibitor Market Size by Therapies in Italy, in USD million (2020-2034)
• Table 61: KRAS Inhibitor Market Size by Therapies in Spain, in USD million (2020-2034)
• Table 62: KRAS Inhibitor Market Size by Therapies in the UK, in USD million (2020-2034)
• Table 63: KRAS Inhibitor Market Size by Therapies in EU4 and the UK, in USD million (2020-2034)
• Table 64: Total KRAS Inhibitor Market Size inhibitors in Japan, in USD million (2020-2034)
• Table 65: KRAS Inhibitor Market Size by Therapies in Japan, in USD million (2020-2034)

List of Figures

• Figure 1: Total Incident Cases of NSCLC in the United States (2020-2034)
• Figure 2: KRAS Incident Cases in NSCLC in the United States (2020-2034)
• Figure 3: KRAS Variant Cases in NSCLC in the United States (2020-2034)
• Figure 4: Total Incident Cases of NSCLC in EU4 and the UK (2020-2034)
• Figure 5: KRAS Incident Cases in NSCLC in EU4 and the UK (2020-2034)
• Figure 6: KRAS Variant Cases in NSCLC in EU4 and the UK (2020-2034)
• Figure 7: Total Incident Cases of NSCLC in Japan (2020-2034)
• Figure 8: KRAS Incident Cases in NSCLC in Japan (2020-2034)
• Figure 9: KRAS Variant Cases in NSCLC in Japan (2020-2034)
• Figure 10: Total Incident Cases of CRC in the United States (2020-2034)
• Figure 11: KRAS Incident Cases in CRC in the United States (2020-2034)
• Figure 12: KRAS Variant Cases in CRC in the United States (2020-2034)
• Figure 13: Total Incident Cases of CRC in EU4 and the UK (2020-2034)
• Figure 14: KRAS Incident Cases in CRC in EU4 and the UK (2020-2034)
• Figure 15: KRAS Variant Cases in CRC in EU4 and the UK (2020-2034)
• Figure 16: Total Incident Cases of CRC in Japan (2020-2034)
• Figure 17: KRAS Incident Cases in CRC in Japan (2020-2034)
• Figure 18: KRAS Variant Cases in CRC in Japan (2020-2034)
• Figure 19: Total Incident Cases of Pancreatic Cancer in the United States (2020-2034)
• Figure 20: KRAS Incident Cases in Pancreatic Cancer in the United States (2020-2034)
• Figure 21: KRAS Variant Cases in Pancreatic Cancer in the United States (2020-2034)
• Figure 22: Total Incident Cases of Pancreatic Cancer in EU4 and the UK (2020-2034)
• Figure 23: KRAS Incident Cases in Pancreatic Cancer in EU4 and the UK (2020-2034)
• Figure 24: KRAS Variant Cases in Pancreatic Cancer in EU4 and the UK (2020-2034)
• Figure 25: Total Incident Cases of Pancreatic Cancer in Japan (2020-2034)
• Figure 26: KRAS Incident Cases in Pancreatic Cancer in Japan (2020-2034)
• Figure 27: KRAS Variant Cases in Pancreatic Cancer in Japan (2020-2034)
• Figure 28: Total Market Size of KRAS-inhibitors in the 7MM, in USD million (2020-2034)
• Figure 29: Market Size of KRAS-inhibitors by Therapies in the 7MM, in USD million (2020-2034)
• Figure 30: Total Market Size of KRAS-inhibitors in the United States, in USD million (2020-2034)
• Figure 31: Market Size of KRAS by Therapies in the United States, in USD million (2020-2034)
• Figure 32: Total Market Size of KRAS-inhibitors in EU4 and the UK, in USD million (2020-2034)
• Figure 33: Market Size of KRAS by Therapies in EU4 and the UK, in USD million (2020-2034)
• Figure 34: Total Market Size of KRAS inhibitors in Japan, in USD million (2020-2034)
• Figure 35: Market Size of KRAS by Therapies in Japan, in USD million (2020-2034)
• Figure 36: Unmet Needs
• Figure 37: Health Technology Assessment
• Figure 38: Reimbursement Process in Germany
• Figure 39: Reimbursement Process in France
• Figure 40: Reimbursement Process in Italy
• Figure 41: Reimbursement Process in Spain
• Figure 42: Reimbursement Process in the United Kingdom
• Figure 43: Reimbursement Process in Japan

Key Highlights:

• Among the 7MM, the United States captured the highest KRAS inhibitors market size in 2023, accounting for nearly 70% of the total KRAS Inhibitor market share.
• Among the approved KRAS Inhibitor therapies in the United States, KRAZATI is expected to have the edge over LUMAKRAS in revenue generated during the study period (2020-2034).
• KRAZATI has been added as a therapeutic option after the first-line for treatment of NSCLC in the latest NCCN guidelines published in December 2022.
• LUMAKRAS witnessed a decrease in sales, coinciding with the launch of KRAZATI. Amgen stated that the decline in sales was primarily due to a price adjustment implemented as part of a reimbursement agreement in Germany.
• In February 2024, Bristol Myers Squibb announced that the US FDA accepted for priority review the sNDA for KRAZATI in combination with cetuximab for the treating KRASG12C-mutated locally advanced or metastatic CRC. The FDA assigned a Prescription Drug User Fee Act (PDUFA) goal date of June 21, 2024.
• There is an opportunity for emerging KRAS companies to shift their focus toward safer combinations with less toxicity.
• The United States had the highest number of KRAS mutation cases in NSCLC among the 7MM. Approximately 46% of all KRAS mutation cases in NSCLC in the 7MM were reported in the United States.
• Identifying G12C inhibitors has sparked interest in developing novel inhibitors targeting other prevalent KRAS mutations. Clinical development efforts are underway to explore alternative strategies for targeting KRAS beyond G12C inhibitors, such as cancer vaccines, adoptive cell therapy, PROTACs, and CRISPR/Cas9.
• Companies involved in researching and developing Pan-KRAS drugs like Cardiff oncology (onvansertib), Gritstone bio (SLATE KRAS), Hookipa pharma (HB-700), and others are expected to have tremendous market potential due to the broad target patient population they can address.
• Many pharmaceutical companies have recently jumped into the KRAS G12D target race. Clinical studies for Phase I of Mirati's KRAS G12D have been approved. Astellas is the newest contender in the KRAS G12D league.
• In a nutshell, it is estimated that the KRAS inhibitor market landscape will experience significant changes during the forecast period of 2024-2034. The potential for combination therapies involving KRAS inhibitors further enhances their market growth prospects. Combining KRAS inhibitors with other targeted therapies, immunotherapies, or chemotherapy may lead to synergistic effects and improved treatment outcomes. However, developing inhibitors that effectively target all KRAS mutant subtypes remains a challenge.

DelveInsight's "KRAS inhibitors Market Insights, Epidemiology, and Market Forecast - 2034" report delivers an in-depth understanding of the KRAS inhibitors, historical and forecasted epidemiology as well as the KRAS inhibitors market trends in the United States, EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan.

KRAS inhibitors market report provides current treatment practices, emerging drugs, market share of individual therapies, and current and forecasted 7MM KRAS inhibitors market size from 2020 to 2034. The report also covers current KRAS inhibitors treatment practices/algorithms and unmet medical needs to curate the best opportunities and assess the market's potential.

KRAS Inhibitors Treatment Market

KRAS inhibitors Overview

KRAS belongs to a group of small GTP-binding proteins known as the RAS superfamily or RAS-like GTPases. Rat sarcoma virus (RAS), an oncogene, functions as a signal transducer, important for regulating cell proliferation, differentiation, and survival in normal and malignant cells. The RAS-mitogen-activated protein kinase-ERK kinase-extracellular signal-related kinase (RAS-RAF-MEK-ERK) pathway is one of the best-characterized signal transduction pathways, and its aberrancies are commonly implicated in the development of multiple different cancer types. KRAS mutations are genetic alterations in the KRAS gene, which encodes a protein in cell signaling pathways. These mutations are commonly found in various types of cancer, including colorectal, lung, and pancreatic cancer. Unfortunately, KRAS mutations have historically been challenging to target with specific treatments. However, recent advancements in research have led to the development of some promising strategies to treat KRAS-mutated cancers, but these treatments are limited to NSCLC only.

Generally, treatment for KRAS-mutated cancers includes surgery, radiation therapy, chemotherapy, targeted therapies, immunotherapy, and others. Radiofrequency ablation (RFA) might be considered for some people with small lung tumors near the outer edge of the lungs, especially if they cannot tolerate surgery.

KRAS Epidemiology

As the KRAS Inhibitor market is derived using a patient-based model, the KRAS inhibitors epidemiology chapter in the report provides historical as well as forecasted epidemiology segmented by total incident cases of NSCLC, CRC, and Pancreatic Cancer, total KRAS incident cases in NSCLC, CRC, and Pancreatic Cancer, total KRAS variant cases in NSCLC, CRC, and Pancreatic Cancer in the 7MM covering the United States, EU4 (Germany, France, Italy, and Spain), United Kingdom, and Japan from 2020 to 2034.

• The total KRAS-mutated cases in the 7MM comprised more than ~490,000 cases in 2023 and are projected to increase during the forecast period.
• Among the selected cancer types, the most KRAS mutant cases are found in Colorectal Cancer, followed by Pancreatic Cancer and NSCLC. In the United States, there were about ~151,000 cases of KRAS mutant colorectal cancer in 2023.
• The most frequent KRAS variant observed in NSCLC is G12C. In addition, the most common KRAS variation in CRC and pancreatic cancer is G12D. In the United States, KRASG12C is present in ~37% of NSCLC cases. The highest rates of KRASG12D, i.e., ~42% and ~30%, were found in pancreatic cancer and CRC, respectively.
• In Japan, the contribution of KRAS mutations is lower compared to Western countries like the United States and Europe.

KRAS Inhibitors Drug Chapters

The drug chapter segment of the KRAS inhibitors reports encloses a detailed analysis of KRAS inhibitors marketed drugs such as LUMAKRAS/LUMYKRAS and KRAZATI, and late-stage (Phase III and Phase II) pipeline drugs including JDQ443, Avutometinib, and others . It also helps understand the KRAS inhibitors clinical trial details, expressive pharmacological action, agreements and collaborations, approval and patent details, advantages and disadvantages of each included drug and the latest news and press releases.

Marketed KRAS Inhibitor Drugs

LUMAKRAS/LUMYKRAS (sotorasib): Amgen

LUMAKRAS is an inhibitor of the RAS GTPase family indicated for treating adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC who have received at least one prior systemic therapy. The drug received accelerated approval from the FDA in May 2021 for treating patients with KRAS G12C-mutated locally advanced or metastatic NSCLC, as determined by an FDA-approved test, following at least one prior systemic therapy. Marketing authorization was subsequently granted in the European Union and additional countries, including some under FDA's Project Orbis initiative, such as Canada and the UK. Additional marketing applications are also under review. Approval was based on pivotal CodeBreaK 100 data demonstrating durable responses and a favorable benefit-risk profile with sotorasib. LUMAKRAS is marketed as LUMYKRAS in the European Union, the United Kingdom, and Switzerland. In August 2023, Amgen announced that the US FDA granted BTD to LUMAKRAS.

KRAZATI (adagrasib): Mirati Therapeutics

KRAZATI is an oral targeted treatment option for adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC, as determined by an FDA-approved test, who have received at least one prior systemic therapy. KRAZATI received approval from the FDA and launched commercially in the US in December 2022. Approval was based on KRYSTAL-1, a multicenter, single-arm, open-label clinical trial (NCT03785249). Recently, in January 2024, the EC granted conditional marketing authorization for KRAZATI for treating KRASG12C -mutated advanced NSCLC and disease progression after at least one prior systemic therapy.

Emerging KRAS Inhibitor Drugs

JDQ443: Novartis

JDQ443 is an investigational covalent KRAS G12C inhibitor derived from a structure-based drug design followed by extensive optimization of two dissimilar prototypes. It is a stable atropisomer containing a unique 5-methyl pyrazole core and a spiro-azetidine linker designed to position the electrophilic acrylamide for optimal engagement with KRAS G12C. JDQ443 inhibits this mutated form of KRAS structurally distinctly, trapping KRAS G12C in a GDP-bound, inactive state while avoiding direct interaction with H95, a recognized route for resistance. Currently, this drug is in a Phase III trial (NCT05132075/KontRASt-02) designed to compare JDQ443 as monotherapy to docetaxel in participants with advanced NSCLC harboring a KRAS G12C mutation who have been previously treated with a platinum-based chemotherapy and immune checkpoint inhibitor therapy either in sequence or in combination. The company has anticipated the data readout of the Phase III monotherapy (2/3L) trial and NDA submission by 2024.

Divarasib: Roche/Genentech

Divarasib (GDC-6036/RO7435846) is an investigational, oral, highly potent, and selective KRAS G12C inhibitor. It works by irreversibly locking the KRAS G12C oncoprotein in its inactive state, preventing the tumor cells from growing. It is being investigated in solid tumors, including non-small cell lung cancer, colorectal cancer, and other cancer types. Preclinical models showed potent and selective inhibition of the KRAS G12C protein. GDC-6036 is designed to selectively bind to the switch II pocket of KRASG12C protein through a specific interaction with the cysteine residue at position 12 and irreversibly lock it in the inactive GDP-bound state. As per the company, a confirmatory pivotal Phase III trial in 2L+ NSCLC was initiated in Q4 2022.

KRAS Inhibitors Market Outlook

KRAS is a well-known oncogene highly prone to mutations in various cancers, including PDAC, NSCLC, and CRC. These mutations are associated with poor prognosis and high fatality rates. The discovery of driver genes and the development of specific inhibitors have significantly transformed cancer treatment approaches and improved clinical outcomes. Targeted therapies have been shown to prolong progression-free survival and exhibit lower toxicity than standard chemotherapy. However, despite several decades of research, there have been limited effective strategies for targeting KRAS mutations, except for recent advancements like sotorasib and adagrasib, which have been approved to target a specific mutated form of KRAS known as KRAS (G12C). Targeting KRAS directly has been a formidable challenge due to its intrinsic characteristics. As a result, researchers have explored alternative approaches, such as targeting downstream signaling molecules, employing epigenetic methods like telomerase inhibitors and RNA interference, and utilizing synthetic lethality strategies involving cyclin-dependent kinase inhibitors.

Until May 2021, no effective treatments were available to counteract the cancer-promoting actions of mutant KRAS proteins. The FDA granted accelerated approval to a drug called LUMAKRAS (sotorasib) to address this issue. LUMAKRAS is designed to treat patients with non-small cell lung cancer (NSCLC) that has either spread locally (locally advanced) or to distant parts of the body (metastatic). These patients must have previously undergone at least one other systemic cancer treatment, such as chemotherapy, and possess a specific KRAS mutation known as G12C in their tumors.

In December 2022, the US FDA granted accelerated approval to KRAZATI (adagrasib), a RAS GTPase family inhibitor, for treating adult patients with locally advanced or metastatic NSCLC carrying the KRAS G12C mutation. This approval was contingent on the results of the KRYSTAL-1 clinical trial, which involved 112 patients. These patients had previously undergone platinum-based chemotherapy and treatment with an immune checkpoint inhibitor, and their disease had progressed.

Amgen and Mirati Therapeutics are at the forefront of the race to develop KRAS inhibitors for cancer treatment. However, their current candidates are focused solely on targeting G12C-mutant tumors, leaving a significant gap in addressing other KRAS variants. This represents a major unmet need in the field, as no approved treatments are currently available for other variants. Recognizing this challenge, numerous key players actively explore alternative KRAS variants and expand their research to include other cancers beyond NSCLC. This shift in focus holds promising potential for developing effective therapies that can address a wider range of KRAS mutations and target multiple cancer types. Many companies are focusing on developing their candidates in pan-KRAS, like Cardiff Oncology (onvansertib), Gritstone bio (SLATE KRAS), Hookipa Pharma (HB-700), and others.

• In the 7MM, the total KRAS Inhibitor market size was approximately USD 500 million in 2023, which is expected to rise significantly by 2034, expected to be mainly driven by increasing incidence, rise in awareness and access to treatment, and robust pipeline activity for cancer indications in the 7MM.
• Since the majority of treatments for NSCLC now target the G12C variant, this variant type is likely to become very crowded and competitive. NSCLC dominates the market due to the availability of approved drugs specifically designed for the G12C mutant NSCLC Future opportunities in G12C may be found in R/R patient's pool of approved KRAS drugs and in the first-line setting.
• Among the approved drugs, KRAZATI is expected to capture more market share than LUMAKRAS throughout the study period (2020-2034).
• Amgen initially held the distinction of being the first company to have a KRAS inhibitor approved in the market. However, their reign was short-lived as adagrasib, followed by sotarasib, obtained regulatory approval the following year.
• Of the emerging therapies, the KRAS Inhibitor products which are anticipated to be launch earliest in the 7MM are; JDQ443, Divarasib, (GDC-6036), and Onvansertib among others.
• Among the emerging KRAS Inhibitor therapies, SLATE-KRAS/v2 + OPDIVO is expected to generate the highest revenue by 2034.

KRAS inhibitors Drugs Uptake

This section focuses on the uptake rate of potential KRAS Inhibitor drugs expected to be launched in the KRAS Inhibitor market during 2020-2034. Further detailed analysis of emerging therapies and drug uptake is in the report.

KRAS Inhibitors Pipeline Development Activities

The KRAS Inhibitor market report provides insights into different therapeutic candidates in Phase III, Phase II, and Phase I stage. It also analyzes key players involved in developing targeted therapeutics.

Pipeline development activities

The KRAS Inhibitor market report covers information on collaborations, acquisitions and mergers, licensing, and patent details for KRAS inhibitors emerging therapies.

KRAS Inhibitor KOL Views

To keep up with current market trends, we take KOLs and SMEs' opinions working in the domain through primary research to fill the data gaps and validate our secondary research. Industry experts were contacted for insights on KRAS inhibitors evolving treatment landscape, patient reliance on conventional therapies, patient therapy switching acceptability, drug uptake, along with challenges related to accessibility.

Delveinsight's analysts connected with 50+ KOLs to gather insights; however, interviews were conducted with 15+ KOLs in the 7MM. Centers such as MD Anderson Cancer Center, Texas from UT Southwestern Medical Center in Dallas, Cancer Research UK Barts Centre in London, MD Anderson Cancer Center, etc., were contacted. Their opinion helps understand and validate current and emerging therapy treatment patterns or KRAS inhibitors market trends. This will support the clients in potential upcoming novel treatments by identifying the overall scenario of the market and the unmet needs.

Qualitative Analysis

We perform Qualitative and market Intelligence analysis using various approaches, such as SWOT 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.

KRAS Inhibitor Market Access and Reimbursement

Reimbursement of rare disease therapies can be limited due to lack of supporting policies and funding, challenges of high prices, lack of specific approaches to evaluating rare disease drugs given limited evidence, and payers' concerns about budget impact. The high cost of rare disease drugs usually has a limited impact on the budget due to the small number of eligible patients being prescribed the drug. The US FDA has approved several rare disease therapies in recent years. From a patient perspective, health insurance and payer coverage guidelines surrounding rare disease treatments restrict broad access to these treatments, leaving only a small number of patients who can bypass insurance and pay for products independently. 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.

Mirati Therapeutics is committed to helping patients and their loved ones gain access to prescribed Mirati medications. When a patient enrolls in the Mirati & Me patient support program, the patient receives the resources and information to help them access their medication, manage costs, and navigate care, including coverage and access support, financial support, educational support, and emotional support.

Amgen's Assist 360 program helps patients reimburse their therapy costs low on their pocket. If the patient has government insurance (like Medicare), Amgen Assist 360 can refer them to independent, nonprofit patient assistance programs that may be able to help them afford their LUMAKRAS copay costs.

Scope of the KRAS Inhibitor Market Report

• The KRAS Inhibitor market report covers a segment of key events, an executive summary, and a descriptive overview of KRAS inhibitors, explaining its causes, signs and symptoms, pathogenesis, and currently available therapies.
• Comprehensive insight into the epidemiology segments and forecasts, the future growth potential of diagnosis rate, disease progression, and treatment guidelines have been provided.
• Additionally, an all-inclusive account of the current and emerging therapies and the elaborative profiles of late-stage and prominent therapies will impact the current treatment landscape.
• A detailed review of the KRAS inhibitors market, historical and forecasted market size, market share by therapies, detailed assumptions, and rationale behind our approach is included in the report, covering the 7MM drug outreach.
• The report provides an edge while developing business strategies, by understanding trends, through SWOT analysis and expert insights/KOL views, patient journey, and treatment preferences that help shape and drive the 7MM KRAS inhibitors market.

KRAS inhibitors market report insights

• KRAS Targeted Patient Pool
• Therapeutic Approaches
• KRAS inhibitors Pipeline Analysis
• KRAS inhibitors Market Size
• KRAS Inhibitor Market Trends
• Existing and future KRAS Inhibitor Market Opportunity

KRAS inhibitors Market Report key strengths

• 11 years Forecast
• The 7MM Coverage
• KRAS inhibitors Epidemiology Segmentation
• Key Cross Competition
• KRAS Inhibitor Drugs Uptake
• Key KRAS Inhibitor Market Forecast Assumptions

KRAS inhibitors Market Report assessment

• Current Treatment Practices
• KRAS Inhibitor Unmet Needs
• KRAS Inhibitor Pipeline Product Profiles
• KRAS Inhibitor Market Attractiveness
• Qualitative Analysis (SWOT)

Key Questions:

KRAS Inhibitor Market insights

• What was the KRAS mutated cancers total market size, the market size by therapies, market share (%) distribution in 2023, and what would it look like in 2034? What are the contributing factors for this growth?
• How will KRAZATI affect the treatment paradigm in NSCLC?
• What will be the market share of NSCLC, CRC, and Pancreatic Cancer in 2034?
• Which KRAS Inhibitor drug is going to be the largest contributor in 2034?
• What are the pricing variations among different geographies for approved KRAS Inhibitor therapies?

KRAS Inhibitor Epidemiology insights

• What are the disease risk, burdens, and unmet needs of KRAS inhibitors? What will be the growth opportunities across the 7MM with respect to the patient population pertaining to KRAS inhibitors?
• What is the historical and forecasted KRAS inhibitors patient pool in the United States, EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan?
• Which type of KRAS mutation is the largest contributor in patients affected with NSCLC, CRC, and Pancreatic Cancer?
• Among EU4 and the UK, which country will have the highest number of patients during the forecast period?
• What are the key findings pertaining to the KRAS mutant Cancer epidemiology across the 7MM, and which country will have the highest number of patients during the forecast period?

Current treatment scenario, marketed drugs, and emerging therapies

• Which are the approved KRAS inhibitors? What are the current treatment guidelines for treating KRAS-mutated cancers in the US and Europe?
• How many KRAS Inhibitor companies are developing therapies for the treatment of KRAS-mutated cancers?
• How many emerging therapies are in the mid-stage and late stage of development for treating KRAS-mutated cancers?
• What are the recent novel therapies, targets, mechanisms of action, and technologies developed to overcome the limitation of existing therapies?
• What key designations have been granted for the emerging therapies for KRAS inhibitors?
• What is the cost burden of approved therapies on the patient?
• Patient acceptability in terms of preferred treatment options as per real-world scenarios?
• What are the country-specific accessibility issues of expensive, recently approved KRAS Inhibitor therapies?

Reasons to buy:

• The KRAS Inhibitor market report will help develop business strategies by understanding the latest trends and changing treatment dynamics driving the KRAS inhibitors Market.
• Insights on patient burden/disease prevalence, evolution in diagnosis, and factors contributing to the change in the epidemiology of KRAS-mutated cancers during the forecast years.
• Understand the existing KRAS Inhibitor market opportunity in varying geographies and the growth potential over the coming years.
• Distribution of historical and current patient share based on real-world prescription data along with reported sales of approved products in the US, EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan.
• Identifying strong upcoming KRAS Inhibitor companies in the market will help devise strategies to help get ahead of competitors.
• Detailed analysis and ranking of class-wise potential current and emerging therapies under the Conjoint analysis section to provide visibility around leading classes.
• Highlights of Access and Reimbursement policies of approved therapies, barriers to accessibility of expensive off-label therapies, and patient assistance programs.
• To understand Key Opinion Leaders' perspectives around the accessibility, acceptability, and compliance-related challenges of existing treatment to overcome barriers in the future.
• Detailed insights on the unmet need of the existing KRAS Inhibitor market so that the upcoming players can strengthen their development and launch strategy.

Table of Contents

1. Key Insights

2. Report Introduction

3. Executive Summary of KRAS Inhibitors

4. Key Events

5. KRAS Inhibitors Market Overview At A Glance

• 5.1. Market Share (%) Distribution of KRAS Inhibitors By Therapy in 2023
• 5.2. Market Share (%) Distribution of KRAS Inhibitors By Therapy in 2034

6. Background And Overview

7. Target Population

8. KRAS Inhibitors Marketed Drugs

• 8.1. Key Competitors
• 8.2. Company 1: Product 1
  • 8.2.1. Product Description
  • 8.2.2. Regulatory Milestones
  • 8.2.3. Other Developmental Activities
  • 8.2.4. Ongoing Clinical Development
  • 8.2.5. Safety and Efficacy
• 8.3. Company 2: Product 2
  • 8.3.1. Product Description
  • 8.3.2. Regulatory Milestones
  • 8.3.3. Other Developmental Activities
  • 8.3.4. Ongoing Clinical Development
  • 8.3.5. Safety and Efficacy

9. KRAS Inhibitors Emerging Drugs

• 9.1. Key Competitors
• 9.2. Company 1: Product 1
  • 9.2.1. Product Description
  • 9.2.2. Other Development Activities
  • 9.2.3. Clinical Development
    • 9.2.3.1. Clinical Trials Information
  • 9.2.4. Safety and Efficacy
• 9.3. Company 2: Product 2
  • 9.3.1. Product Description
  • 9.3.2. Other Development Activities
  • 9.3.3. Clinical Development
    • 9.3.3.1. Clinical Trials Information
  • 9.3.4. Safety and Efficacy

10. KRAS Inhibitors Market: The 7MM Analysis

• 10.1. Key Findings
• 10.2. KRAS Inhibitor Market Outlook
• 10.3. Key KRAS Inhibitor Market Forecast Assumptions
• 10.4. Total KRAS Inhibitor Market Size in the 7MM
  • 10.4.1. KRAS Inhibitor Market Size By Therapies In the 7MM
  • 10.4.2. KRAS Inhibitor Market Size By Indication In the 7MM
• 10.6. United States: KRAS Inhibitor Market
  • 10.6.1. Total KRAS Inhibitor Market Size in the United States
  • 10.6.2. KRAS Inhibitor Market Size By Therapies in the United States
• 10.7. EU4 and the UK: KRAS Inhibitor Market
  • 10.7.1. Total KRAS Inhibitor Market Size in EU4 and the UK
  • 10.7.2. KRAS Inhibitor Market Size By Therapies in EU4 and the UK
• 10.8. Japan: KRAS Inhibitor Market
  • 10.8.1. Total KRAS Inhibitor Market Size in Japan
  • 10.8.2. KRAS Inhibitor Market Size By Therapies in Japan

11. KRAS Inhibitor Unmet Needs

12. KRAS Inhibitor SWOT Analysis

13. KRAS Inhibitor KOL Views

14. KRAS Inhibitor Market Access and Reimbursement

• 14.1. United States
  • 14.1.1. Centre for Medicare & Medicaid Services (CMS)
• 14.2. EU4 and the UK
  • 14.2.1. Germany
  • 14.2.2. France
  • 14.2.3. Italy
  • 14.2.4. Spain
  • 14.2.5. United Kingdom
• 14.3. Japan
  • 14.3.1. MHLW

15. Appendix

• 15.1. Bibliography
• 15.2. Report Methodology

16. Delveinsight Capabilities

17. Disclaimer

18. About DelveInsight