癌症治疗中的抗体药物偶联物

Antibody-Drug Conjugatesin Cancer Therapy IQVIA Ark Patent Intelligence — September 2025. NEHA RANI,SENIOR INSIGHTS ASSOC, ARK PATENT INTELLIGENCE, IQVIATARISHI GUPTA,SENIOR INSIGHTS ASSOC, ARK PATENT INTELLIGENCE, IQVIA Table of contents Introduction1Structural insights on ADCs and their mechanism of action2ADC development3ADC landscape via Ark Patent Intelligence4Case study 1: Strategic insights into Kadcyla and Enhertu5Case study 2: Strategic insights into Adcetris and Polivy6Conclusions7References7About the authors8 Introduction Cancer remains one of the most formidable healthchallenges, affecting millions of lives across everycorner of the globe.1The World Health Organisation’s2024 report recorded 20 million new cancer casesand 9.7 million deaths in 2022, with projectionsreaching 35 million cases by 2050.2Conventionalcancer treatment options were quite systemicand non-specific, leading to side effects. Overdecades, a remarkable shift towards more targetedand personalized therapies have led to the use ofantibody-drug conjugates (ADCs) as a promisingtherapy for cancer.1 Today, ADCs have proven to be game changers incancer therapy with growing market needs.1The firstADC drug approval, Pfizer’s MylotargTM (Gemtuzumabozogamicin) by the US Food and Drug Administration(FDA) in 2000 for treating acute myeloid leukaemia(AML), marked a milestone in precision oncology.4 The European Medicines Agency (EMA) followed withapproval in 2018, granting it orphan drug status dueto the rarity of AML.5The USA ADC market, valued atUSD 11.3 billion in 2023, is projected to grow rapidly inthe upcoming years.6 Ark Patent Intelligence offers comprehensive insightsinto the global ADC drug market. It provides extensiveworldwide information on drug approvals, marketinsights, key patents, regulatory protections, litigationtrends, and detailed in-depth analyses of marketed,registered and phase III drugs covering more than30 ADCs. ADCs are advanced therapies that link monoclonalantibodies (mAbs) to potent cytotoxic drugs, known aspayloads, via cleavable or non-cleavable linkers. Theydeliver drugs directly to cancer cells by recognizingspecific antigens, thereby minimizing harm to healthytissue, and enabling a bystander effect that killsnearby tumour cells.1Despite their promise, ADCsare complex and costly to develop, with challenges,including off-target toxicity and drug resistance.Currently, 15 ADCs are approved for various cancers,such as breast, blood, gastric, urothelial, cervical, andlung cancers (Figure 1),1and around 200 are in clinicaltrials, including 24 in Phase III, all driven by advancesin antibody, linker, and payload technologies.3 Despite their promise, ADCs are complex and costly to develop,with challenges, including off-target toxicity and drug resistance.Currently, 15 ADCs are approved for various cancers, such as breast,blood, gastric, urothelial, cervical, and lung cancers and around200 are in clinical trials. Notes: Different payloads used - MMAE: Monomethyl auristatin E; PE38: A 38kD fragment of Pseudomonas exotoxin A; MMAF: Monomethylauristatin-F; IRDye700DX: Near-infrared phthalocyanine dye; PBD dimer: Pyrrolobenzodiazepine; SN38: Active metabolite of Irinotecan; DM1:Mertansine or Emtansine, derivative of maytansine 1; TOP1- Topoisomerase I; DXd: Exatecan derivative for ADC; DM4: Ravtansine, a modifiedform of maytansine. Different targets used – CD: Cluster of differentiation of various cell surface molecules - CD30, CD79b, CD22, CD19 and CD33; c-Met receptor-Mesenchymal-Epithelial Transition Factor; HER2- Human Epidermal growth factor Receptor 2; BCMA- B Cell Maturation Antigen; EGFR- EpidermalGrowth Factor Receptor; TROP-2- Trophoblast cell surface antigen 2. Over 70% use cleavable linkers that respond to acidicor enzymatic environments in lysosomes, like those inMylotarg and Enhertu®. Non-cleavable linkers, seen inKadcyla®, offer greater plasma stability and release thepayload only after cancer cell internalization.1,3,4Thecytotoxic payload is the core active component of ADCs,spanning various drug classes. Tubulin binders are themost widely used, present in 53.3% of approved ADCsand 45.8% of Phase III candidates. Other payloadsinclude DNA-damaging agents and Topoisomerase I(TOP1) inhibitors. A key design metric in ADC is theDrug-to-Antibody Ratio (DAR), typically rangingbetween 0 and 8 in approved ADCs, balancing potencywith safety.3 Structural insights on ADCsand their mechanismof action ADCs consist of three key components a mAb, alinker, and a payload.1,3The mAb component identifiesTumour-Associated antigens (T-Ags) via its Fragmentantigen binding (Fab) region and can trigger immuneresponses such as Complement-Dependent Cytotoxicity(CDC), Antibody-Dependent Cellular Cytotoxicity(ADCC), and Antibody-Dependent Cellular Phagocytosis(ADCP), inducing cell death through apoptosis ornecrosis (Figure 2).7,8Linkers in ADCs connect theantibody to the payload, enabling controlled release. The lates