Review of FDA-Approved ADC Drugs up to 2024

Review of FDA-Approved ADC Drugs up to 2024

Since 2000, the research and development of precision therapy represented by small molecule targeted drugs and antibodies has made great progress and become the main targeted therapy for tumors. However, since small molecules and antibody drugs can specifically target tumor signaling pathways or antigens on the surface of tumor cells, and the heterogeneity between tumor cells is strong, precision therapy is very important for precision therapy. Antibody drug conjugates (ADCs) combine the dual advantages of small molecule and antibody drugs compared to antibody or small molecule drugs alone. Many ADCs have demonstrated impressive activity against treatment-refractory cancers, resulting in their approval for both hematologic malignancies and solid tumorindications.

What is Antibody Drug Conjugate?

ADCs are hybrid therapies that deliver cytotoxic payloads directly to the desired site of action to enhance efficacy and minimize off-target effects. It consists of three basic components, namely an antibody that recognizes the target antigen, a small molecule cytotoxic drug, and a chemical linker that connects the two. Each factor affects the ultimate efficacy and safety of the ADC. In general, ADC development needs to consider all of these key factors, including the selection of target antigen, antibody, cytotoxic payload, linker, and conjugation method. After ADC drugs enter the blood, they work through the following main steps: 1) The monoclonal antibody first binds to the target antigen highly expressed on the surface of tumor cells; 2) The tumor cells internalize the ADC-antigen conjugate into the cells; 3 ) The linker is digested by lysosomes in the cell, and the linker is cleaved, releasing small molecule cytotoxic drugs; 4) Cytotoxicity plays a role in destroying DNA or preventing tumor cells from dividing, killing cells; 5) The synergistic effect of monoclonal antibodies, because they bind the target antigen, will also play the role of targeted drugs, such as HER-2 antibodies.

modular components of ADC drug Fig. 1. The modular components of an antibody-drug conjugate (Front Pharmacol. 2023, 14: 1274088).

FDA Approved Antibody Drug Conjugates (ADCs) by 2024

After decades of research and troubleshooting, significant technological advancements and an improved mechanistic understanding of ADC activity culminated in the FDA approval of 15 ADCs, each providing demonstrable therapeutic benefit to cancer patients. Of these, belantamab mafodotin-blmf (Blenrep) was withdrawn from the FDA on November 22, 2022.

ADCCommon NameTargetmAbLinkerPayloadPayload ActionDARConjugationCompany
Mylotarg Gemtuzumab OzogamicinCD33IgG4Acid CleavableOzogamicin/ CalicheamicinDNA Cleavage2-3LysinePfizer
AdcetrisBrentuximab VedotinCD30IgG1Enzyme CleavableMMAE/ AuristatinMicrotubule Inhibitor4CysSeattle
Kadcyla Adotrastuzumab EmtansineHER2IgG1Non-CleavableDM1/ MaytansinoidMicrotubule Inhibitor3.5LysineRoche
BesponsaInotuzumab OzogamicinCD22IgG4Acid CleavableOzogamicin/ CalicheamicinDNA Cleavage6LysinePfizer
Polivy Polatuzumab Vedotin-piiqCD79bIgG1Enzyme CleavableMMAE/ AuristatinMicrotubule Inhibitor3.5CysRoche
LumoxitiMoxetumomab PasudotoxCD22-Enzyme CleavablePseudomonas Exotoxin A--CysAstrazeneca
Padcev Enfortumab Vedotin-ejfvNectin4IgG1Enzyme CleavableMMAE/ AuristatinMicrotubule Inhibitor3.8CysSeattle
EnhertuFamtrastuzumab DeruxtecannxkHER2IgG1Enzyme CleavableDXd/ CamptothecinTOP1 Inhibitor8CysDaiichi Sankyo
Trodelvy Sacituzumab
TROP2IgG1Acid CleavableSN-38/ CamptothecinTOP1 Inhibitor7.6CysImmunomedics
BCMAIgG1Non-CleavableMMAF/ AuristatinMicrotubule Inhibitor4CysGSK
Zynlonta Loncastuximab
CD19IgG1Enzyme CleavableSG3199/ PBD DimerDNA Cleavage2.3CysADC Therapeutics
AkaluxCetuximab SaratolacanEGFR-----LysineRakuten Medical
Aidixi Disitamab VedotinHER2IgG1Enzyme CleavableMMAEMicrotubule Inhibitor4CysRemeGen
TivdakTisotumab Vedotin-tftvTissue FactorIgG1Enzyme CleavableMMAE/ AuristatinMicrotubule Inhibitor4CysSeagen
Elahere Mirvetuximab SoravtansineFRαIgG1Cleavable Disufide LinkerDM4Microtubule Inhibitor3.5LysineImmunoGen

Table 1. FDA approved ADCs.

ADC Formulation Analysis

A typical antibody formulation contains ADC, excipients (sugars or salts), buffers, surfactants (Tween) and other metal ion chelators. Table 2 lists the formulations of ADCs that have been marketed, which show that even with the same linker-payload, the final formulation buffer used by different antibodies will be different.

ADCSpecification/BottleConcentrationBuffer Salt/mLExcipients/mLSurfactants/mLpH
Mylotarg 4.5 mg1 mg/ml5 mM Phosphate14 mg Sucrose, 8 mg Glucan 40, 5.2 mg Sodium Chloride-7.4
Adcetris50 mg5 mg/ml20 mM Citrate70 mg Trehalose Dihydrate0.2 mg Tween806.6
Kadcyla 100 mg, 160 mg20 mg/ml10 mM Succinic acid60 mg Sucrose0.2 mg Tween805.0
Besponsa1 mg0.25 mg/ml18 mM Tromethamine45 mg Sucrose, 5.2 mg Sodium Chloride0.1 mg Tween808.0
Lumoxiti 1 mg1 mg/ml25 mM Phosphate40 mg Sucrose, 80 mg Glycine0.2 mg Tween807.4
Polivy140 mg20 mg/ml8 mM Succinic Acid40 mg Sucrose1 mg Tween805.3
Padcev 23 mg, 33 mg10 mg/ml20 mM Histidine55 mg Trehalose Dihydrate0.2 mg Tween806.0
Enhertu100 mg20 mg/ml25 mM Histidine90 mg Sucrose0.3 mg Tween805.5
Trodelvy 180 mg10 mg/ml18 mM MES7.8 mg Trehalose Dihydrate0.1 mg Tween806.5
Blenrep100 mg50 mg/ml20 mM Citrate75.6 mg Trehalose Dihydrate0.2 mg Tween806.2
Akalux 250 mg5 mg/ml10 mM Sodium Phosphate90 mg Trehalose0.2 mg Tween807.1
Zynlonta10 mg5 mg/ml20 mM Histidine59.9 mg Sucrose0.2 mg Tween806.0
Aidixi 60 mg10 mg/ml10 mM Histidine43.72 mg Mannitol, 20.54 mg Sucrose0.2 mg Tween806.1
Tivdak40 mg10 mg/ml30 mM Histidine30 mg Mannitol, 30 mg Sucrose-6.0

Table 2. ADCs formulation analysis.

Screening Process for ADC Preparations

  • pH and Buffer Screening

Among the 14 ADCs on the market, most ADCs have pH values between 6.0 and 6.9. Among them, histidine salt was the most important buffer type. Among the 14, 5 were histidine, 3 phosphate, 2 citrate, 2 succinate, 1 tromethamine and 1 MES. Generally, the selection of ADC buffer needs to follow the following principles: according to the buffer range of different buffer pairs, the pH gradient was set from 4.0-8.0 to prepare the ADC concentration for clinical use. Then, they were placed at 25°C and 40°C for 7 days, observed and sampled on day 0, day 1, day 3 and day 7, respectively, including observation of clarity, BCA detection concentration, SEC-HPLC detection of purity, DSC detection of thermal stability, etc.

When the suitable pH range is determined, two buffers at the pH can be selected. For example, when the suitable pH is 6.0, 30 mM histidine or 20 mM citric acid can be selected as the buffering agent of the preparation, and then the next step is screened.

ADCBuffer Salt/mLConfiguration/mLpH
Mylotarg 5 mM Phosphate0.52 mg disodium hydrogen phosphate anhydrous, 0.09 mg sodium dihydrogen phosphate monohydrate7.4
Adcetris20 mM Citrate5.6 mg sodium citrate dihydrate, 0.21 mg citric acid monohydrate6.6
Kadcyla 10 mM Succinic Acid-5.0
Besponsa18 mM Tromethamine2.15 mg tromethamine8.0
Lumoxiti 25 mM Phosphate3.4 mg water sodium bicarbonate phosphate7.4
Polivy8 mM Succinic Acid1 mg Succinic Acid5.3
Padcev 20 mM Histidine1.40 mg L-histidine, 2.31 mg L-histidine hydrochloride6.0
Enhertu25 mM Histidine0.89 mg L-histidine, 4.04 mg L-histidine hydrochloride5.5
Trodelvy 18 mM MES3.8 mg MES6.5
Blenrep20 mM Citrate0.42 mg citric acid, 6.7 mg disodium and trisodium citrate dihydrate6.2
Akalux 10 mM Sodium Phosphate-7.1
Zynlonta20 mM Histidine1.4 mg L-histidine, 2.3 mg L-histidine hydrochloride6.0
Aidixi 10 mM Histidine2.1 mg histidine hydrochloride (adjusted with NaOH)6.1
Tivdak30 mM Histidine2.11 mg L-histidine, 3.44 mg L-histidine hydrochloride6.0

Table 3. ADCs pH and buffer analysis.

  • Surfactant Screening

Surfactants reduce aggregate production primarily by reducing surface tension. Of the 14 ADCs, 7 used 0.01-0.02% (W/V) Tween 80, 3 used 0.01-0.02% (W/V) Tween 20, and 1 used 0.03% Tween 80, 1 used 0.1% Tween 20, and the other 2 did not add surfactant. Generally, there are two screening principles for surfactants.

  • Common processing method: stir the sample horizontally at 250-300 rpm on an orbital shaker at 25°C for 8 hours or longer. After stirring, some samples will aggregate and the solution will become cloudy.
  • Reference detection methods: visual observation of solution clarity, concentration determination, SEC-HPLC detection of aggregate content, turbidity meter detection of turbidity, HIAC automatic liquid particle counter detection of particle number.
  • Excipient Screening

Among the 14 ADC formulations, various sugars or salts were added as excipients mainly. When setting different sugars and salts, there are many combinations and types. 10% trehalose, 9% sucrose, 5% sorbitol, etc. can be used as the basic formula for preliminary screening. When it is necessary to combine, the content of the two is halved. After 14 days of storage at 4°C, 25°C, and 40°C, characterizations were performed for transparency observation, BCA concentration detection, SEC-HPLC purity detection, DSC thermal stability detection, CIEF pH detection, etc.

Featured ADC Services from BOC Sciences

ADC Linkers DevelopmentLinkers play a crucial role in determining the stability, specificity, and efficacy of ADCs. BOC Sciences offers a range of linker development services, including the design and synthesis of novel linkers with properties such as improved stability, cleavability and selectivity.
Antibody Modification and Conjugation BOC Sciences also provides expertise in antibody modification and conjugation technologies, including modifying antibodies to introduce reactive groups for conjugation with cytotoxic payloads, and conjugating antibodies to payloads using a variety of chemistries and techniques.
ADC Analysis and CharacterizationOnce an ADC is developed, its properties must be analyzed and characterized to ensure that it meets the required specifications for stability, potency, and specificity. BOC Sciences offers a range of analytical and characterization services for ADCs, including mass spectrometry, chromatography and bioanalytical assays.
ADC Linker and Cytotoxin ConjugationsBOC Sciences also offers linker and cytotoxic conjugation services to antibodies, a process that involves synthesizing and conjugating cytotoxic payloads to antibodies using a variety of chemistries and techniques.
ADC Payloads DevelopmentBOC Sciences has a team of experienced chemists and pharmacologists who can design and synthesize novel payloads to meet the specific needs of each project.
ADC ManufactureOnce an ADC is developed and optimized, it is important to produce the therapeutic in a scalable and reproducible manner. BOC Sciences provides manufacturing services for ADCs, including process development, scale-up and cGMP production.
ADC Development for TargetsBOC Sciences provides services for target-specific ADC development. This involves the identification and validation of the ADC target antigen, as well as the design and optimization of the antibody composition.


  1. Kavianinia, I. et al. An insight into FDA approved antibody-drug conjugates for cancer therapy. Molecules. 2021, 26: 5847.
  2. Riccardi, F. et al. A comprehensive overview on antibody-drug conjugates: from the conceptualization to cancer therapy. Front Pharmacol. 2023, 14: 1274088.
* Only for research. Not suitable for any diagnostic or therapeutic use.
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