519:
benefit in sicker, high-risk patients but did show a statistical benefit in all patient subgroups. Although the patient population as a whole contained many very sick individuals and thus there were many adverse events in both the subjects receiving placebo and those receiving bezlotoxumab, the panel focused on a small number of serious events in patients with pre-existing congestive heart failure. In this subset the patients receiving bezlotoxumab appeared to have a higher rate of negative outcomes than the placebo group, although there may have been an imbalance in how sick the patients in those groups were.
480:
interact with bezlotoxumab, but appears to interact with B1, which is representative of the entire CROP domain. Bezlotoxumab interacts with either B2 and B3 or the overlapping residues region between the two domains. The B4 fragment does not interact with the specific portion of the CROP domain. Characterization of peptide B1 as full CROP domain of TcdB suggests that the antibody specifically reacts with the B2 region of the CROP domain. This leads to the conclusion that the TcdB epitope lies within the N-terminus of the CROP domain.
1567:
514:'s Antimicrobial Drugs Advisory Committee (formerly known as the Anti-Infective Drugs Advisory Committee) met to discuss bezlotoxumab. The committee voted to recommend approval of Merck's license application by a vote of 10 to 5, generally expressing a willingness to accept that the trials had proven that bezlotoxumab decreased recurrence of
479:
and a combined repetitive oligopeptides, CROP domain. The CROP domain consists of four different peptide units: B1, B2, B3, and B4. Bezlotoxumab specifically inhibits the CROP domain of TcdB. It recognizes a specific epitope on toxin TcdB and has high affinity for that region. The GTD domain does not
518:
overall. The committee tempered this acceptance with a robust discussion of whether or not the drug provide more marked benefit in some patient groups and expressed concern over a potential safety signal in the group treated with bezlotoxumab. The data suggested that bezlotoxumab might have the most
522:
Bezlotoxumab gained FDA approval in
October 2016: "indicated to reduce the recurrence of Clostridium difficile infection (CDI) in patients 18 years of age or older who are receiving antibiotics for CDI and are at high risk for recurrence."
894:
722:"Merck & Co., Inc., Medarex, Inc. and Massachusetts Biologic Laboratories Sign Exclusive Licensing Agreement for Investigational Monoclonal Antibody Combination for Clostridium Difficile Infection"
625:
Orth P, Hernandez LD, Reichert P, Sheth PR, Beaumont M, Yang XY, Murgolo N, Ermakov G, DiNunzio E, Racine F, Karczewskl J, Secore S, Ingram RN, Mayhood T, Strickland C, Therien AG (27 June 2014).
235:
887:
1418:
880:
190:
804:
540:
1411:
88:
739:
787:
753:
566:
493:
1597:
740:"Pivotal Phase 3 Studies of Bezlotoxumab, Merck's Investigational Antitoxin to Prevent Clostridium Difficile Infection Recurrence, Met Primary Endpoint"
36:
1404:
503:
A Phase III trial only showed a benefit from bezlotoxumab; the combination of actoxumab and bezlotoxumab worked no better to prevent recurrence of
1362:
773:
592:
680:
Lowy I, Molrine DC, Leav BA, Blair BM, Baxter R, Gerding DN, Nichol G, Thomas WD, Leney M, Sloan S, Hay CA, Ambrosino DM (January 2010).
460:
456:
972:
472:
64:
220:
120:
1587:
1557:
852:
822:
758:
599:
511:
341:
139:
816:
1464:
1379:
1446:
492:, was developed through Phase II efficacy trials by a partnership between Medarex Inc and MassBiologics of the
1454:
1367:
987:
176:
1544:
1469:
1459:
1107:
1012:
872:
721:
846:
788:"Briefing Information for the June 9, 2016 Meeting of the Antimicrobial Drugs Advisory Committee (AMDAC)"
1437:
1042:
1002:
903:
754:"Antimicrobial Drugs Advisory Committee (Formerly known as the Anti-Infective Drugs Advisory Committee)"
1592:
183:
1501:
451:
285:
46:
29:
1156:
978:
907:
150:
603:
1249:
1123:
703:
662:
476:
261:
248:
78:
294:
693:
652:
642:
386:
350:
1571:
1396:
1373:
657:
626:
497:
1581:
1529:
1328:
112:
98:
1428:
1312:
993:
983:
203:
198:
541:"Prescription medicines: registration of new chemical entities in Australia, 2017"
1539:
1534:
1514:
1344:
1273:
1257:
1223:
1218:
1179:
1174:
1169:
1146:
1103:
1083:
1078:
1073:
1048:
1033:
1028:
1018:
998:
968:
106:
593:"Statement On A Nonproprietary Name Adopted By The USAN Council - Bezlotoxumab"
1524:
1239:
1164:
1098:
1093:
1068:
1063:
1058:
1053:
1023:
1008:
425:
325:
631:
Toxin B-neutralizing
Antibody Bezlotoxumab Revealed by X-ray Crystallography"
22:
1519:
1487:
1479:
1302:
1213:
1198:
1184:
1113:
1088:
1038:
963:
934:
647:
489:
92:
707:
682:"Treatment with monoclonal antibodies against Clostridium difficile toxins"
666:
698:
681:
305:
134:
314:
475:(TcdB), the toxin was identified to consist of three domains: a GTD, a
58:
919:
370:
1287:
1141:
1136:
1131:
948:
911:
51:
567:"Prescription medicines and biologicals: TGA annual summary 2017"
361:
267:
242:
1400:
876:
255:
129:
805:
FDA Approves
Zinplava for Recurrent C. difficile. Oct 25 2016
229:
161:
847:"Drug Approval Package: Zinplava Injection (bezlotoxumab)"
1555:
1500:
1478:
1445:
1436:
1337:
1321:
1295:
1286:
1266:
1248:
1232:
1206:
1197:
1155:
1122:
956:
947:
927:
918:
424:
385:
380:
360:
340:
324:
304:
284:
279:
219:
214:
189:
175:
149:
119:
105:
87:
77:
72:
57:
45:
35:
28:
471:By x-ray crystallized structure of N-terminal of
500:for further development and commercialization.
293:
728:. Merck Sharp & Dohme Corp. 21 April 2009.
1412:
888:
507:associated diarrhea than bezlotoxumab alone.
454:designed for the prevention of recurrence of
8:
138:
21:
1442:
1419:
1405:
1397:
1292:
1203:
953:
924:
895:
881:
873:
494:University of Massachusetts Medical School
697:
656:
646:
349:
774:"FDA Panel Favors New C. Diff. Biologic"
1562:
532:
313:
111:
571:Therapeutic Goods Administration (TGA)
545:Therapeutic Goods Administration (TGA)
20:
627:"Mechanism of Action and Epitopes of
97:
7:
202:
742:(Press release). 20 September 2015.
496:. The project was then licensed to
369:
1598:Drugs developed by Merck & Co.
14:
1427:Immune sera and immunoglobulins (
817:"Drug Trials Snapshots: Zinplava"
1565:
473:Clostridioides difficile toxin B
467:Mechanism of TcdB neutralization
403:
397:
635:Journal of Biological Chemistry
415:
409:
391:
1:
853:Food and Drug Administration
823:Food and Drug Administration
759:Food and Drug Administration
600:American Medical Association
498:Merck Sharp & Dohme Corp
446:, sold under the brand name
1465:Hepatitis B immune globulin
1614:
381:Chemical and physical data
1357:
457:Clostridioides difficile
1455:Anthrax immune globulin
648:10.1074/jbc.m114.560748
1545:Tixagevimab/cilgavimab
1470:Zoster-immune globulin
1460:Rho(D) immune globulin
973:+maftivimab/odesivimab
488:This drug, along with
1588:Monoclonal antibodies
1502:Monoclonal antibodies
1438:Polyclonal antibodies
904:Monoclonal antibodies
699:10.1056/NEJMoa0907635
629:Clostridium difficile
65:Clostridium difficile
606:on 16 September 2012
762:. 18 February 2021.
641:(26): 18008–18021.
452:monoclonal antibody
251:(Prescription only)
238:(Prescription only)
30:Monoclonal antibody
25:
16:Monoclonal antibody
1384:Never to phase III
908:infectious disease
794:. 9 February 2019.
510:In June 2016, the
1553:
1552:
1496:
1495:
1394:
1393:
1353:
1352:
1282:
1281:
1193:
1192:
943:
942:
857:. 21 October 2016
827:. 21 October 2016
477:cysteine protease
441:
440:
271:
259:
246:
233:
165:
132:
1605:
1570:
1569:
1568:
1561:
1443:
1421:
1414:
1407:
1398:
1293:
1204:
954:
925:
897:
890:
883:
874:
867:
866:
864:
862:
843:
837:
836:
834:
832:
813:
807:
802:
796:
795:
784:
778:
777:
770:
764:
763:
750:
744:
743:
736:
730:
729:
718:
712:
711:
701:
677:
671:
670:
660:
650:
622:
616:
615:
613:
611:
602:. Archived from
597:
589:
583:
582:
580:
578:
563:
557:
556:
554:
552:
537:
436:
434:
417:
411:
405:
399:
393:
373:
353:
317:
297:
269:
266:
257:
254:
244:
241:
231:
228:
206:
163:
160:
142:
131:
128:
115:
101:
26:
24:
1613:
1612:
1608:
1607:
1606:
1604:
1603:
1602:
1578:
1577:
1576:
1566:
1564:
1556:
1554:
1549:
1492:
1474:
1432:
1425:
1395:
1390:
1389:
1374:Clinical trials
1349:
1333:
1317:
1278:
1262:
1244:
1228:
1189:
1151:
1118:
939:
914:
901:
871:
870:
860:
858:
845:
844:
840:
830:
828:
815:
814:
810:
803:
799:
786:
785:
781:
772:
771:
767:
752:
751:
747:
738:
737:
733:
720:
719:
715:
686:N. Engl. J. Med
679:
678:
674:
624:
623:
619:
609:
607:
595:
591:
590:
586:
576:
574:
565:
564:
560:
550:
548:
539:
538:
534:
529:
486:
469:
432:
430:
420:
414:
408:
402:
396:
376:
356:
336:
320:
300:
275:
210:
178:
171:
152:
145:
17:
12:
11:
5:
1611:
1609:
1601:
1600:
1595:
1590:
1580:
1579:
1575:
1574:
1551:
1550:
1548:
1547:
1542:
1537:
1532:
1527:
1522:
1517:
1512:
1506:
1504:
1498:
1497:
1494:
1493:
1491:
1490:
1484:
1482:
1476:
1475:
1473:
1472:
1467:
1462:
1457:
1451:
1449:
1440:
1434:
1433:
1426:
1424:
1423:
1416:
1409:
1401:
1392:
1391:
1388:
1387:
1386:
1385:
1382:
1371:
1365:
1359:
1358:
1355:
1354:
1351:
1350:
1348:
1347:
1341:
1339:
1335:
1334:
1332:
1331:
1325:
1323:
1319:
1318:
1316:
1315:
1310:
1305:
1299:
1297:
1290:
1284:
1283:
1280:
1279:
1277:
1276:
1270:
1268:
1264:
1263:
1261:
1260:
1254:
1252:
1246:
1245:
1243:
1242:
1236:
1234:
1230:
1229:
1227:
1226:
1221:
1216:
1210:
1208:
1201:
1195:
1194:
1191:
1190:
1188:
1187:
1182:
1177:
1172:
1167:
1161:
1159:
1153:
1152:
1150:
1149:
1144:
1139:
1134:
1128:
1126:
1120:
1119:
1117:
1116:
1111:
1101:
1096:
1091:
1086:
1081:
1076:
1071:
1066:
1061:
1056:
1051:
1046:
1036:
1031:
1026:
1021:
1016:
1006:
996:
991:
981:
976:
966:
960:
958:
951:
945:
944:
941:
940:
938:
937:
931:
929:
922:
916:
915:
902:
900:
899:
892:
885:
877:
869:
868:
838:
808:
797:
779:
776:. 9 June 2016.
765:
745:
731:
713:
692:(3): 197–205.
672:
617:
584:
573:. 21 June 2022
558:
547:. 21 June 2022
531:
530:
528:
525:
485:
482:
468:
465:
439:
438:
428:
422:
421:
418:
412:
406:
400:
394:
389:
383:
382:
378:
377:
375:
374:
366:
364:
358:
357:
355:
354:
346:
344:
338:
337:
335:
334:
330:
328:
322:
321:
319:
318:
310:
308:
302:
301:
299:
298:
290:
288:
282:
281:
277:
276:
274:
273:
264:
252:
239:
225:
223:
217:
216:
212:
211:
209:
208:
195:
193:
187:
186:
181:
179:administration
173:
172:
170:
169:
167:
157:
155:
147:
146:
144:
143:
125:
123:
117:
116:
109:
103:
102:
95:
85:
84:
81:
75:
74:
70:
69:
61:
55:
54:
49:
43:
42:
41:Whole antibody
39:
33:
32:
15:
13:
10:
9:
6:
4:
3:
2:
1610:
1599:
1596:
1594:
1591:
1589:
1586:
1585:
1583:
1573:
1563:
1559:
1546:
1543:
1541:
1538:
1536:
1533:
1531:
1530:Obiltoxaximab
1528:
1526:
1523:
1521:
1518:
1516:
1513:
1511:
1508:
1507:
1505:
1503:
1499:
1489:
1486:
1485:
1483:
1481:
1477:
1471:
1468:
1466:
1463:
1461:
1458:
1456:
1453:
1452:
1450:
1448:
1444:
1441:
1439:
1435:
1430:
1422:
1417:
1415:
1410:
1408:
1403:
1402:
1399:
1383:
1381:
1378:
1377:
1375:
1372:
1369:
1366:
1364:
1361:
1360:
1356:
1346:
1343:
1342:
1340:
1336:
1330:
1329:Obiltoxaximab
1327:
1326:
1324:
1320:
1314:
1311:
1309:
1306:
1304:
1301:
1300:
1298:
1294:
1291:
1289:
1285:
1275:
1272:
1271:
1269:
1265:
1259:
1256:
1255:
1253:
1251:
1247:
1241:
1238:
1237:
1235:
1231:
1225:
1222:
1220:
1217:
1215:
1212:
1211:
1209:
1205:
1202:
1200:
1196:
1186:
1183:
1181:
1178:
1176:
1173:
1171:
1168:
1166:
1163:
1162:
1160:
1158:
1154:
1148:
1145:
1143:
1140:
1138:
1135:
1133:
1132:Cosfroviximab
1130:
1129:
1127:
1125:
1121:
1115:
1112:
1109:
1105:
1102:
1100:
1097:
1095:
1092:
1090:
1087:
1085:
1082:
1080:
1077:
1075:
1072:
1070:
1067:
1065:
1062:
1060:
1057:
1055:
1052:
1050:
1047:
1044:
1040:
1037:
1035:
1032:
1030:
1027:
1025:
1022:
1020:
1017:
1014:
1010:
1007:
1004:
1000:
997:
995:
992:
989:
985:
982:
980:
977:
974:
970:
967:
965:
962:
961:
959:
955:
952:
950:
946:
936:
933:
932:
930:
926:
923:
921:
917:
913:
909:
905:
898:
893:
891:
886:
884:
879:
878:
875:
856:
854:
848:
842:
839:
826:
824:
818:
812:
809:
806:
801:
798:
793:
789:
783:
780:
775:
769:
766:
761:
760:
755:
749:
746:
741:
735:
732:
727:
726:Press Release
723:
717:
714:
709:
705:
700:
695:
691:
687:
683:
676:
673:
668:
664:
659:
654:
649:
644:
640:
636:
632:
630:
621:
618:
605:
601:
594:
588:
585:
572:
568:
562:
559:
546:
542:
536:
533:
526:
524:
520:
517:
513:
508:
506:
501:
499:
495:
491:
483:
481:
478:
474:
466:
464:
462:
459:
458:
453:
450:, is a human
449:
445:
429:
427:
423:
390:
388:
384:
379:
372:
368:
367:
365:
363:
359:
352:
348:
347:
345:
343:
339:
332:
331:
329:
327:
323:
316:
312:
311:
309:
307:
303:
296:
292:
291:
289:
287:
283:
278:
272: Rx-only
265:
263:
253:
250:
240:
237:
227:
226:
224:
222:
218:
213:
205:
200:
197:
196:
194:
192:
188:
185:
182:
180:
174:
168:
159:
158:
156:
154:
148:
141:
136:
127:
126:
124:
122:
118:
114:
110:
108:
104:
100:
96:
94:
90:
86:
82:
80:
76:
73:Clinical data
71:
67:
66:
62:
60:
56:
53:
50:
48:
44:
40:
38:
34:
31:
27:
19:
1510:Bezlotoxumab
1509:
1313:Suvratoxumab
1308:Bezlotoxumab
1307:
1142:Porgaviximab
1137:Larcaviximab
1043:+casirivimab
1013:+tixagevimab
994:Bebtelovimab
984:Bamlanivimab
859:. Retrieved
850:
841:
829:. Retrieved
820:
811:
800:
791:
782:
768:
757:
748:
734:
725:
716:
689:
685:
675:
638:
634:
628:
620:
608:. Retrieved
604:the original
587:
575:. Retrieved
570:
561:
549:. Retrieved
544:
535:
521:
516:C. difficile
515:
509:
505:C. difficile
504:
502:
487:
470:
455:
447:
444:Bezlotoxumab
443:
442:
295:1246264-45-8
221:Legal status
215:Legal status
140:Bezlotoxumab
121:License data
63:
23:Bezlotoxumab
18:
1593:Antibiotics
1540:Raxibacumab
1535:Palivizumab
1515:Motavizumab
1370:from market
1345:Urtoxazumab
1274:Tefibazumab
1258:Pagibaximab
1224:Raxibacumab
1219:Panobacumab
1180:Palivizumab
1175:Motavizumab
1170:Lenvervimab
1147:Vilobelimab
1108:+cilgavimab
1104:Tixagevimab
1084:Regdanvimab
1079:Regavirumab
1074:Rafivirumab
1049:Libivirumab
1034:Foravirumab
1029:Exbivirumab
1019:Diridavumab
999:Casirivimab
988:+etesevimab
979:Avdoralimab
969:Atoltivimab
437: g·mol
280:Identifiers
184:Intravenous
107:MedlinePlus
79:Trade names
1582:Categories
1525:Nirsevimab
1240:Edobacomab
1165:Felvizumab
1099:Suptavumab
1094:Sotrovimab
1069:Pemivibart
1064:Odesivimab
1059:Nirsevimab
1054:Maftivimab
1024:Etesevimab
1009:Cilgavimab
1003:+imdevimab
610:25 October
527:References
461:infections
426:Molar mass
351:4H5YMK1H2E
326:ChemSpider
286:CAS Number
1520:Nebacumab
1488:Antivenom
1480:Antiserum
1380:Phase III
1368:Withdrawn
1338:Humanized
1303:Actoxumab
1267:Humanized
1214:Nebacumab
1199:Bacterial
1185:Suvizumab
1157:Humanized
1114:Tuvirumab
1089:Sevirumab
1039:Imdevimab
964:Ansuvimab
935:Efungumab
490:actoxumab
177:Routes of
151:Pregnancy
99:Monograph
93:Drugs.com
1572:Medicine
1322:Chimeric
1250:Chimeric
1124:Chimeric
861:26 March
831:26 March
708:20089970
667:24821719
577:31 March
512:U.S. FDA
448:Zinplava
306:DrugBank
191:ATC code
166: B2
153:category
135:DailyMed
83:Zinplava
658:4140266
551:9 April
484:History
387:Formula
315:DB13140
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920:Fungal
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1296:Human
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1233:Mouse
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949:Viral
928:Human
855:(FDA)
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596:(PDF)
52:Human
1447:IVIG
910:and
906:for
863:2020
833:2020
704:PMID
663:PMID
612:2012
579:2024
553:2023
413:2014
407:1726
401:9974
395:6464
362:KEGG
342:UNII
333:none
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37:Type
1429:J06
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