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Universitäts-Augenklinik Bonn
Anti-VEGF-Therapie: Lucentis
Frank G. Holz
www.augenklinik.uni-bonn.de
AAD 200623. März 2006Minisymposium 175
Neutralisierung von VEGFNeutralisierung von VEGF
Antikörperfragment: Ranibizumab = Lucentis
Antikörper: Bevacizumab = Avastin
Aptamer: Ranibizumab = Macugen
Daniel W. Miller, Silvia Vosseler, Nicolae Mirancea, Daniel J. Hicklin, Peter Bohlen , Frank G. Holz, Norbert E. Fusenig. Rapid Vessel Regression, Protease Inhibition, and Stromal Normalization uponShort-Term Vascular Endothelial Growth Factor Receptor 2 Inhibition in Skin CarcinomaHeterotransplants. American Journal of Pathology 2005;167:1389-1403
Blockade of VEGF receptor 2 (VEGFR-2)with the monoclonal antibody DC101
LucentisLucentis
MARINA-Studie okkulte und minimal klassische CNV
ANCHOR-Studie überwiegend klassische CNV
Reading center confirmsangiographic eligibility
Randomized 1:1:1
Sham(n=238)
Ranibizumab 0.3 mg(n=238)
Ranibizumab0.5 mg(n=240)
Minimally classic oroccult with no classic lesions
(n=716)
Investigator identifiespotential patients
Lucentis: MARINALucentis: MARINA--StudieStudieOkkulte + minimal klassische CNVOkkulte + minimal klassische CNV
2 4 6 8 10 12
Visit (months)-15
-10
-5
0
5
10
ETD
RS
lette
rs
Sham (n=238)Ranibizumab 0.3 mg (n=238)Ranibizumab 0.5 mg (n=240)
-10.4
+6.5+7.2 17.6 letter
benefit ***
16.9 letter benefit ***
Visual acuity mean change from baseline (letters)Visual acuity mean change from baseline (letters)
***P<0.0001 for all ranibizumab comparisons vs Sham from month 1 to month 24
Lucentis: MARINALucentis: MARINA--Studie 1 JahrStudie 1 Jahr
Lucentis: MARINALucentis: MARINA--StudieStudie
***p < 0.0001 vs. Sham
15,110,9
5,911,3
38,734,5
15,0
40,0 42,1
0
10
20
30
40
50
60
70
80
90
100
Baseline Month 12 Month 24
*** ******
***
Sham (n=238)
Ranibizumab 0.3 mg (n=238)
Ranibizumab 0.5 mg (n=240)
Patients with Patients with 20/4020/40 or better (%)or better (%)
*** ***
Reading center confirmsangiographic eligibility
Randomized 1:1:1
Predominantly classic lesions (n=423)
Investigator identifiespotential subjects
Verteporfin ShamPDT
ShamPDT
Shaminjection(n=143)
Ranibizumab 0.3 mg(n=140)
Ranibizumab0.5 mg(n=140)
Lucentis ANCHOR-StudieÜÜberwiegende klass. CNV: Lucentis vs. PDTberwiegende klass. CNV: Lucentis vs. PDT
Lucentis ANCHOR-StudieÜÜberwiegende klass. CNV: Lucentis vs. PDTberwiegende klass. CNV: Lucentis vs. PDT
Ranibizumab0.5 mg
Primary endpoint
Sham injection
0.3 mg
0 1 2 3 4 5 6 7 8 9 10 11 12Month
0.5 mg
Ranibizumab0.3 mg
PDT
Sham PDTVerteporfin
Sham
LucentisLucentis
ANCHOR
Patients losing <15 letters (%)
MARINA
Verteporfin(n=143)
64.3
Sham(n=238)
62.2
***p<0.0001 vs control
Ranibizumab0.3 mg(n=140)
Ranibizumab0.5 mg(n=139)
Ranibizumab0.3 mg(n=238)
Ranibizumab0.5 mg(n=240)
*** *** *** ***94.3 96.494.5 94.6
0
100
EXCITEEXCITE--StudieStudie
Month
Ranibizumab0.3 mg
Ranibizumab0.5 mg
0 1 2 3 4 5 6 7 8 9 10 11 12 23 24
Finalvisit
PrimaryEndpoint
Ranibizumab0.3 mg
LucentisLucentis PROTECTPROTECT--StudieStudieLucentisLucentis + PDT+ PDT
• Investigator discretion• Ranibizumab administered 1 hr after verteporfin PDT
1 2 3 4 5 6 7 8 9
PDT
0Month
Ranibizumab+
** ** **
Primary endpoint
Intraokulare EntzIntraokulare Entzüündungndung
MARINA ANCHOR
1 (0.7%)1 (0.7%)00002 (0.8%)2 (0.8%)2 (0.8%)2 (0.8%)00Intraocular inflammationIntraocular inflammation
000000000000VitritisVitritis
1 (0.4%)1 (0.4%)
1 (0.4%)1 (0.4%)
00
RanibizumabRanibizumab0.5 mg0.5 mg(n=239)(n=239)
00
1 (0.4%)1 (0.4%)
1 (0.4%)1 (0.4%)
RanibizumabRanibizumab0.3 mg0.3 mg(n=238)(n=238)
00
00
00
ShamSham(n=236)(n=236)
1 (0.7%)1 (0.7%)0000UveitisUveitis
000000IridocyclitisIridocyclitis
0 0 0000IritisIritis
RanibizumabRanibizumab0.5 mg0.5 mg(n=140)(n=140)
RanibizumabRanibizumab0.3 mg0.3 mg(n=137)(n=137)
VerteporfinVerteporfin(n=143)(n=143)MedDRAMedDRA
preferred termspreferred terms
Integrated safety summary
APTC arterial APTC arterial thromboembolicthromboembolic events: events: Pooled ANCHOR and MARINAPooled ANCHOR and MARINA
APTC* classificationAPTC* classificationSham or Sham or
vertaporfinvertaporfin(n=379) (n=379)
RanibizumabRanibizumab0.3 mg 0.3 mg (n=375)(n=375)
Ranibizumab Ranibizumab 0.5 mg 0.5 mg (n=379)(n=379)
Vascular death Vascular death 1 (0.3%)1 (0.3%) 2 (0.5%)2 (0.5%) 3 (0.8%)3 (0.8%)
NonNon--fatalfatalmyocardial infarction myocardial infarction 2 (0.5%)2 (0.5%) 2 (0.5%)2 (0.5%) 4 (1.0%)4 (1.0%)
NonNon--fatalfatalischemic stroke ischemic stroke 2 (0.5%)2 (0.5%) 2 (0.5%)2 (0.5%) 4 (1.0%)4 (1.0%)
NonNon--fatalfatalhemorrhage stroke hemorrhage stroke 00 00 00
TOTALTOTAL 5 (1.3%)5 (1.3%) 6 (1.6%)6 (1.6%) 11 (2.9%)11 (2.9%)
*Used during FDA COX-2 inhibitor advisory panel meetings Feb’05
Integrated safety summary*Antiplatelet Trialists’ Collaboration, BMJ 1994 Jan 8; 308(6921): 81
SchluSchlußßfolgerungenfolgerungenWirksamkeitWirksamkeit
•• AntiAnti--VEGFVEGF--Therapiestrategie bestTherapiestrategie bestäätigttigt•• Wirksamkeit Wirksamkeit üüber 2 Jahreber 2 Jahre•• Zunahme des Benefits gegenZunahme des Benefits gegenüüber Placebo ber Placebo üüber 2 ber 2
JahreJahre
SicherheitSicherheit•• Sicherheitsprofil okulSicherheitsprofil okulääre Nebenwirkungen +re Nebenwirkungen +•• ExtraokulExtraokulääres Sicherheitsprofil +res Sicherheitsprofil +
•• Keine Evidenz fKeine Evidenz füür systemische VEGFr systemische VEGF--InhibitionInhibition
AusblickAusblick•• Reduzierte Applikationsfrequenz?Reduzierte Applikationsfrequenz?•• Abbruchkriterien?Abbruchkriterien?•• Andere ApplikationssystemeAndere Applikationssysteme
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