Table A2.
Reported PD Biomarkers of approved therapeutic proteins.
| No | Protein Drug | Pharmacodynamic Marker |
|---|---|---|
| 1. | Abatacept (Orencia) | T cell proliferation & co-stimulation [342] |
| 2. | Adalimumab (Humira) | TNF-alpha levels & inflammatory cytokine reduction [343] |
| 3. | Aducanumab (Aduhelm) | Beta-amyloid plaques in the brain [344] |
| 4. | Aflibercept (Eylea) | VEGF levels, Central retinal thickness [345] |
| 5. | Agalsidase Alfa (Replagal) | Lyso-Gb3 levels, Kidney function [346] |
| 6. | Agalsidase Beta (Fabrazyme) | Lyso-Gb3 levels, Kidney function [347] |
| 7. | Albiglutide (Tanzeum) | Blood glucose & GLP-1 levels [348] |
| 8. | Albutrepenonacog Alfa (Idelvion) | Factor IX activity levels [349] |
| 9. | Aldesleukin (Proleukin) | T cell count, IL-2 levels [350] |
| 10. | Alefacept (Amevive) | CD4 and CD8 memory T-cell count [351] |
| 11. | Alemtuzumab (Lemtrada) | CD52-expressing cell count [352] |
| 12. | Alglucerase (Ceredase) | Gaucher cell count, Chitotriosidase levels [353] |
| 13. | Alirocumab (Praluent) | LDL cholesterol levels [354] |
| 14. | Alpha-1-proteinase inhibitor (Prolastin, etc.) | Alpha-1 antitrypsin levels, Neutrophil elastase activity [355] |
| 15. | Alteplase (Activase) | Fibrinolytic activity, clot dissolution [356] |
| 16. | Amivantamab (Rybrevant) | EGFR and MET signaling inhibition [357] |
| 17. | Anakinra (Kineret) | IL-1β levels [358] |
| 18. | Ancestim (Stemgen) | CD34+ cell count in peripheral blood [359] |
| 19. | Andexanet Alfa (Andexxa) | Reversal of factor Xa inhibitors [360] |
| 20. | Anifrolumab (Saphnelo) | Type I interferon gene signature [361] |
| 21. | Anistreplase (Eminase) | Fibrinolytic activity [362] |
| 22. | Ansuvimab (Ebanga) | Reduction in viral load of Ebola virus [363] |
| 23. | Atezolizumab (Tecentriq) | PD-L1 expression on tumor & immune cells [364] |
| 24. | Avelumab (Bavencio) | PD-L1 expression & T cell activation [365] |
| 25. | Benralizumab (Fasenra) | Reduction in eosinophil counts [366] |
| 26. | Bermekimab (Xilonix) | IL-1α levels [367] |
| 27. | Bevacizumab (Avastin) | VEGF level & microvessel density [368] |
| 28. | Bezlotoxumab (Zinplava) | Reduction in C. difficile infection recurrence [369] |
| 29. | Bimekizumab (Bimzelx) | IL-17A and IL-17F levels [370] |
| 30. | Bivalirudin (Angiomax) | Thrombin activity [371] |
| 31. | Blinatumomab (Blincyto) | CD19+ B cell count [372] |
| 32. | Bone Morphogenetic Proteins (BMPs) | Bone density or new bone formation [373] |
| 33. | Botulinum Toxin Type A (Botox) | Neuromuscular transmission inhibition [374] |
| 34. | Botulinum Toxin Type B (Myobloc) | Neuromuscular transmission inhibition [375] |
| 35. | Brodalumab (Siliq) | IL-17 receptor A occupancy [376] |
| 36. | Brolucizumab (Beovu) | VEGF levels, Central retinal thickness [377] |
| 37. | Burosumab (Crysvita) | Serum phosphorus levels [378] |
| 38. | Calaspargase pegol (Asparlas) | Asparagine levels [379] |
| 39. | Canakinumab (Ilaris) | IL-1β levels & CRP [380] |
| 40. | Cetuximab (Erbitux) | EGFR expression & phosphorylation [226] |
| 41. | Chymopapain (Chymodiactin) | Disc volume reduction [381] |
| 42. | Coagulation factor IX (BeneFIX) | Factor IX clotting activity [382] |
| 43. | Coagulation Factor VIIa (NovoSeven) | Clotting activity [383] |
| 44. | Collagenase (Santyl) | Degrades necrotic tissue [384] |
| 45. | Conestat alfa (Ruconest) | Bradykinin levels [385] |
| 46. | Corticotropin (Acthar) | Adrenal gland stimulation [386] |
| 47. | Cosyntropin-ACTH(1-24) (Cortrosyn) | Adrenal gland stimulation [387] |
| 48. | Crizanlizumab (Adakveo) | P-selectin inhibition [388] |
| 49. | Darbepoetin alfa (Aranesp) | Hemoglobin or hematocrit level [389] |
| 50. | Denosumab (Prolia, Xgeva) | RANKL inhibition & bone turnover markers [390] |
| 51. | Denosumab (Prolia) | Bone mineral density & serum C-telopeptide [390] |
| 52. | Dupilumab (Dupixent) | IL-4 and IL-13 signaling pathways [391] |
| 53. | Durvalumab (Imfinzi) | PD-L1 expression in tumor cells [392] |
| 54. | Eculizumab (Soliris) | Complement component C5 activity [393] |
| 55. | Edrecolomab (Panorex) | EpCAM expression [394] |
| 56. | Efalizumab (Raptiva) | CD11a expression [395] |
| 57. | Efgartigimod alfa | IgG reduction [396] |
| 58. | Elapegademase (Revcovi) | ADA enzyme activity [397] |
| 59. | Elosulfase Alfa (Vimizim) | GAG reduction [398] |
| 60. | Elotuzumab (Empliciti) | SLAMF7 expression in myeloma cells [399] |
| 61. | Emapalumab (Gamifant) | IFNγ levels [400] |
| 62. | Emicizumab (Hemlibra) | Factor IXa and factor X bridging [401] |
| 63. | Enfortumab vedotin (Padcev) | Nectin-4 expression [402] |
| 64. | Erenumab (Aimovig) | CGRP receptor binding and inhibition [403] |
| 65. | Erythropoietin (EPO) | Hemoglobin or hematocrit level [404] |
| 66. | Eteplirsen (Exondys 51) | Dystrophin production in muscle tissue [405] |
| 67. | Evolocumab (Repatha) | LDL cholesterol levels [406] |
| 68. | Fibrinolysin (Elase) | Fibrin degradation [407] |
| 69. | Filgrastim (Neupogen) | Neutrophil count [408] |
| 70. | Follitropin (Follistim, Gonal-f) | Follicular development, Estradiol levels [409] |
| 71. | Fremanezumab (Ajovy) | CGRP levels [410] |
| 72. | Galcanezumab (Emgality) | CGRP levels [411] |
| 73. | Galcanezumab (Emgality) | CGRP binding [412] |
| 74. | Galsulfase (Naglazyme) | Urinary glycosaminoglycan levels [413] |
| 75. | Gemtuzumab ozogamicin (Mylotarg) | CD33 antigen expression [414] |
| 76. | Girentuximab | CAIX expression [415] |
| 77. | Glatiramer acetate (Copaxone) | Immune modulation; T-cell response [416] |
| 78. | Glucagon recombinant (GlucaGen) | Blood glucose elevation [417] |
| 79. | Glucarpidase (Voraxaze) | Methotrexate levels reduction [418] |
| 80. | Golimumab (Simponi) | TNFα inhibition [419] |
| 81. | Growth Hormone | IGF-1 (Insulin-like Growth Factor 1) level [420,421] |
| 82. | Guselkumab (Tremfya) | IL-23 levels & PASI score [422] |
| 83. | Human C1-esterase inhibitor (Berinert, Cinryze) | C1-INH levels and activity [423] |
| 84. | Ibalizumab (Trogarzo) | HIV-1 viral load & CD4+ T-cell count [353] |
| 85. | Imiglucerase (Cerezyme) | Glucocerebroside levels, macrophage activity [424] |
| 86. | Inebilizumab (Uplizna) | B-cell depletion [425] |
| 87. | Infliximab (Remicade) | TNF-alpha levels & CRP [426] |
| 88. | Inotuzumab ozogamicin (Besponsa) | CD22 expression [427] |
| 89. | Insulin Regular (Humulin R, etc) | Glucose levels [428] |
| 90. | Interferons | Expression of interferon-responsive genes [429] |
| 91. | Ipilimumab (Yervoy) | T-cell activation [430] |
| 92. | Isatuximab (Sarclisa) | CD38 expression [431] |
| 93. | Itolizumab (Alzumab) | CD6 expression [432] |
| 94. | Ixekizumab (Taltz) | PASI score, serum IL-17A levels [433] |
| 95. | Lanadelumab (Takhzyro) | Plasma kallikrein activity [434] |
| 96. | Lanadelumab (Takhzyro) | Plasma kallikrein inhibition [435] |
| 97. | Laronidase (Aldurazyme) | Reduction of glycosaminoglycans [436] |
| 98. | Lepirudin (Refludan) | Inhibition of thrombin [437] |
| 99. | Leuprolide (Lupron) | Reduction in testosterone or estradiol [438] |
| 100. | Liraglutide (Victoza) | Blood glucose & GLP-1 levels [439] |
| 101. | Lixisenatide (Adlyxin) | GLP-1 receptor activation [440] |
| 102. | Loncastuximab tesirine (Zynlonta) | CD19 expression [441] |
| 103. | Lucinactant (Surfaxin) | Improved lung compliance [441] |
| 104. | Luspatercept-aamt (Reblozyl) | Erythroid maturation [441] |
| 105. | Lutropin alfa (Luveris) | LH receptor activation [442] |
| 106. | Margetuximab (Margenza) | HER2 expression [443] |
| 107. | Mecasermin (Increlex) | IGF-1 receptor activation [444] |
| 108. | Menotropins (Menopur) | FSH and LH receptor activation [445] |
| 109. | Mepolizumab (Nucala) | IL-5 neutralization [446] |
| 110. | Metreleptin (Myalept) | Leptin receptor activation [447] |
| 111. | Mirvetuximab Soravtansine | Folate receptor alpha targeting [448] |
| 112. | Mogamulizumab (Poteligeo) | CCR4 targeting [449] |
| 113. | Moxetumomab pasudotox (Lumoxiti) | CD22 expression [450] |
| 114. | Muromonab (Orthoclone OKT3) | CD3 expression [451] |
| 115. | Natalizumab (Tysabri) | α4-integrin saturation [452] |
| 116. | Naxitamab (Danyelza) | GD2 expression [453] |
| 117. | Necitumumab (Portrazza) | EGFR targeting [454] |
| 118. | Nesiritide (Natrecor) | Natriuretic peptide receptor A activation [455,456] |
| 119. | Netakimab (Netakimab) | IL-17A inhibition [457,458] |
| 120. | Nimotuzumab (Theraloc, h-R3) | EGFR targeting [459,460] |
| 121. | Nivolumab (Opdivo) | PD-1 receptor occupancy & T cell function [233] |
| 122. | Nofetumomab fmerpentan (Verluma) | Carcinoembryonic antigen (CEA) targeting [461] |
| 123. | Obiltoxaximab (Anthim) | Protective antigen (PA) binding of Bacillus anthracis [462] |
| 124. | Obinutuzumab (Gazyva) | CD20 targeting [234] |
| 125. | Ocrelizumab (Ocrevus) | CD20 targeting [463] |
| 126. | Ocriplasmin (Jetrea) | Vitreomacular adhesion dissolution [461] |
| 127. | Ofatumumab (Arzerra) | CD20 targeting [235] |
| 128. | Olaratumab (Lartruvo) | PDGFRα phosphorylation levels [376] |
| 129. | Olipudase alfa (Xenpozyme) | Acid sphingomyelinase replacement [464] |
| 130. | Omalizumab (Xolair) | Free serum IgE levels & FcεRI expression on basophils [465] |
| 131. | Oportuzumab monatox (Vicineum) | N-acetylgalactosamine-4-sulfatase targeting [466] |
| 132. | Oprelvekin (Neumega) | Thrombopoietin receptor activation [467] |
| 133. | Oxytocin (Pitocin) | Oxytocin receptor activation [468] |
| 134. | Palifermin (Kepivance) | Keratinocyte growth factor receptor activation [469] |
| 135. | Palivizumab (Synagis) | RSV neutralization in serum [154] |
| 136. | Pancrelipase amylase (Creon) | Pancreatic enzyme replacement [470] |
| 137. | Panitumumab (Vectibix) | EGFR receptor occupancy & phosphorylation [471,472] |
| 138. | Parathyroid/Preotact (Preos) | Parathyroid hormone (PTH) receptor activation [473] |
| 139. | Pegademase bovine (Adagen) | ADA enzyme replacement [474] |
| 140. | Pegaspargase (Oncaspar) | Asparagine depletion [475] |
| 141. | Pegcetacoplan (Empaveli) | Complement C3 inhibition [476] |
| 142. | Peginterferon alfa-2a (Pegasys) | Interferon alpha receptor activation [477] |
| 143. | Peginterferon alfa-2b (PegIntron) | Interferon alpha receptor activation [478] |
| 144. | Pegloticase (Krystexxa) | Uric acid metabolism [479] |
| 145. | Pegvisomant (Somavert) | Growth hormone receptor antagonist [480] |
| 146. | Pembrolizumab (Keytruda) | PD-1 receptor occupancy & PD-L1 expression [481] |
| 147. | Pertuzumab (Perjeta) | HER2 receptor dimerization inhibition [481] |
| 148. | Pertuzumab (Perjeta) | HER2/neu targeting [482] |
| 149. | Pramlintide (Symlin) | Amylin analogue [483] |
| 150. | Protein S human (PROS) | Protein S supplementation [484] |
| 151. | Ramucirumab (Cyramza) | VEGFR2 targeting [485] |
| 152. | Ranibizumab (Lucentis) | VEGF level & macular thickness [486] |
| 153. | Rasburicase (Elitek) | Uric acid conversion to allantoin [487] |
| 154. | Reteplase (Retavase) | Plasminogen activation [488] |
| 155. | Rilonacept (Arcalyst) | Interleukin-1 blockade [489] |
| 156. | Rituximab (Rituxan) | CD20+ B cell depletion [490] |
| 157. | Romiplostim (Nplate) | Thrombopoietin receptor stimulation [491] |
| 158. | Romosozumab (Evenity) | Sclerostin levels & bone mineral density [492] |
| 159. | Sacrosidase (Sucraid) | Sucrase replacement for sucrose digestion [493] |
| 160. | Sargramostim (Leukine) | GM-CSF receptor activation [494] |
| 161. | Sarilumab (Kevzara) | IL-6 receptor blockade & CRP [495] |
| 162. | Sebelipase alfa (Kanuma) | Lysosomal acid lipase replacement [496] |
| 163. | Secretin (SecreFlo) | Secretin receptor activation [497] |
| 164. | Secukinumab (Cosentyx) | PASI score, serum IL-17A levels [241] |
| 165. | Sermorelin (Geref) | GHRH receptor activation [498] |
| 166. | Siltuximab (Sylvant) | IL-6 targeting [499] |
| 167. | Somatotropin (Genotropin) | GH receptor activation [500] |
| 168. | Streptokinase (Streptase) | Plasminogen activation [501] |
| 169. | Tagraxofusp (Elzonris) | CD123-directed cytotoxin [502] |
| 170. | Taliglucerase alfa (Elelyso) | Glucocerebrosidase enzyme replacement [503] |
| 171. | Teduglutide (Gattex) | GLP-2 receptor activation [504] |
| 172. | Tenecteplase (TNKase) | Plasminogen activation [505] |
| 173. | Teriparatide (Forteo) | Bone formation stimulation [472] |
| 174. | Terlipressin (Varpress) | Vasoconstriction through V1 receptor activation [506] |
| 175. | Tesamorelin (Egrifta) | GH-releasing hormone receptor activation [507] |
| 176. | Thymalfasin (Zadaxin) | Immunomodulation, T-cell stimulation [508] |
| 177. | Thyrotropin Alfa (Thyrogen) | Thyroid-stimulating hormone receptor activation [509] |
| 178. | Tirzepatide (Mounjaro) | Dual GLP-1 and GIP receptor agonism [510] |
| 179. | Tisotumab vedotin (Tivdak) | ADC targeting tissue factor [511] |
| 180. | Tocilizumab (Actemra) | IL-6 receptor blockade [512] |
| 181. | Tositumomab (Bexxar) | CD20 targeting [513] |
| 182. | Trastuzumab (Herceptin) | HER2/neu receptor expression [514] |
| 183. | Urofollitropin (Bravelle) | Follicle-stimulating hormone stimulation [515] |
| 184. | Urokinase (Abbokinase) | Plasminogen activation [516] |
| 185. | Ustekinumab (Stelara) | Inhibition of the p40 subunit of interleukin-12 (IL-12) and interleukin-23 (IL-23) [517] |
| 186. | Vasopressin (Vasostrict) | V1 and V2 receptor activation [518] |
| 187. | Vedolizumab (Entyvio) | α4β7 integrin receptor occupancy [519] |
| 188. | Velaglucerase alfa (Vpriv) | Glucocerebrosidase enzyme replacement [520] |