Real life utilization data for Lucentis in wAMD

Transcription

Use of Real-World Data for Lucentis®
Dirk Sauer, PhD
Global Development Franchise Head Ophthalmology
Novartis Basel
Ranibizumab (Lucentis®)

Ranibizumab (Lucentis®) is a recombinant humanized monoclonal antibody
fragment (Fab)1,2
• Produced in an Escherichia coli expression system (and thus not glycosylated)
• Genetically engineered to increase its affinity for binding and inhibition of VEGF
• Shorter systemic half-life than full-length antibody
 Lucentis®
is approved in over 100 countries for the treatment of wet age
related macular degeneration (wet AMD)
Insertion of murine
anti-VEGF-A sequences
into a human Fab
framework
rhu Fab
Ranibizumab
(48 kDa)
Affinity
maturation2
Affinity enhanced
120–140-fold
Anti-VEGF-A
murine MAb
(~150 kDa)
1.
2.
Novartis Europharm Ltd. Lucentis SmPC. September 2011
Ferrara N et al. Retina 2006;26:859–70
2 │Lucentis® real world data │ Real World Evidence Conference │ Jan 29, 2014
Mass production
in E. coli vector
Visual defects with wet AMD
Wet AMD
Neovascular AMD
Normal
Distortion
Blur
Scotoma
If left untreated, wet AMD leads to progressive vision loss and blindness
In 2006, Lucentis® transformed the way to treat
wet age related macular degeneration
15
+11.3
10
+10.7
+8.1
ETDRS letters
5
+8.5
0
0
2
4
6
8
10
-5
12
Month
-10
16
18
20
22
24
-9.8
Ranibizumab 0.3 mg (n = 140)
-15
14
Ranibizumab 0.5 mg (n = 140)
Verteporfin (n = 143)
-9.6
Lucentis® use in the real world – how does it
compare to clinical trial data ?

Safety

Treatment frequency

Effectiveness
Lucentis® post-marketing exposure up to June 2013
PSUR (years: 01 Jul – 30 Jun), patient treatment years (ptys)
Cumulative
Total (ptys)
Europe
1&2
(20062007)
9,400
3&4
(20072008)
59,700
5&6
(20082009)
95,900
7
(20092010)
134,300
8
(20102011)
171,400
9
(20112012)
227,400
10
(20122013)
283,400
US
68,700#
72,200
84,400
108,100
153,200
151,800
159,900
798,300
ROW
4,700
16,400
33,700
63,700
86,300
106,900
130,300
442,000
Total
82,800#
148,300
214,000
306,100
410,900
486,100
573,600
2,221,800
981,500
*calculated by assuming 6 vials per patient per year
#exposure expressed differently from that presented in PSUR 1 and PSUR 2 as a different method was previously used by Genentech to determine
vials used per patient per year
Each number in the table has been rounded to the nearest 100
Reporting rates for spontaneous post-marketing
AEs and literature cases up to Jun 2013
Safety issue
(Risks based on pivotal clinical trial data and mechanism of action)
Important
identified risks
Important
potential risks
Intraocular inflammation
Hypersensitivity reactions
Endophthalmitis
Cataract
Intraocular pressure increase
Retinal detachment
Retinal pigment epithelial (RPE) tear
Vitreous hemorrhage
Retinal tear
Non-myocardial arterial thromboembolic events
Myocardial infarction
Hypertension
Non-ocular hemorrhage
Deterioration of retinal blood flow including CRAO
Venous thromboembolic events
Glaucoma
Proteinuria
Cumulative reporting rate
(spontaneous and literature reports
per 100,000 patient treatment years)
46
38
37
17
10
9
6
3
2
35
14
12
11
4
3
3
0.4
US claims database comparison of real-world
treatment patterns
1
2
3
• Key objective: to compare the number of doses received and the
frequency of patient visits over the first 12 months of therapy using US
data
• Source: Integrated Data Warehouse (IDW), a large physician-level claims
database managed by IMS Health
• Population: treatment-naïve patients with wAMD (180 days without
treatment prior to index date)
Integrated Data Warehouse
A large physician-level claims database in US
Claims data derived from a
wide range of sources
including pharmacies,
hospitals and healthcare
providers
Integrated
Data
Warehouse
Most claims are available within 3
weeks of a
patient visit
~ 1 billion professional fee claims
per year
> 870 000 practitioners in the USA,
covering 50 states
Physician-based data entry
(ensures representative
patients)
Treatment-naïve patients starting ranibizumab
and followed up for 365 days were included
Diagnosis of wAMD
First claim between
November 2011 and March 2012
No treatment for ≥ 180 days before
index date (treatment-naїve patients)
Follow-up of 365 days
Real-world dosing data from two claims analyses
show similar number of injections over 12 months
Mean number of doses
6
Ranibizumab injections received over first
12 months of treatment
5.4†
4.9*
4
2
0
n = 1898
VERO analysis
*Ferreira A et al. Value Health 2013;16(7):A512; †Johnston SS et al. presented at AAO 2013
Analysis included treatment-naïve AMD patients who did not switch therapies through 12 months.
n = 8519
Marketscan analysis
Real life utilization data for Lucentis® in wAMD
in Canada

Objective:
• To assess the yearly frequency of ranibizumab injections for the treatment of wAMD in
two large Canadian public drug plans: ODB Program and RAMQ

Methodology:
• Patient longitudinal drug utilization database RxDynamics® (IMS Health Canada Inc.)
was used to assess the mean annual number of ranibizumab injections for wAMD
patients covered by the ODB or RAMQ provincial drug plans.
• The capture rate for the ODB and RAMQ patient data was 100% and 75% respectively
• 1 claim was defined as 1 injection.
• Only wAMD treatment-naïve patients who had at least 6 months history in the
provincial drug plan were included.
• Index date was defined as the date of the first ranibizumab claim.
• The analysis looked at patients (by month) from January 2009 to March 2012.
• Mean number of claims during the patient's first, second, and third year of
ranibizumab therapy were tracked.
Real life utilization data for Lucentis® in wAMD
in Canada
Conclusion
• Many ON and QC RS and Ophthalmologists adopt an individualized ranibizumab treatment
regimen to manage their patients’ wAMD – not monthly
• The annual frequency was similar to that observed in clinical trials using monthly follow-up with
clearly defined retreatment criteria
Treatment with Lucentis® has helped to reduce
blindness
50% reduction in the incidence of AMDassociated legal blindness in Denmark
from 52.2 to 25.7 per 100,000 in people
aged ≥50 years1
80
60
EU license of
Lucentis
(Jan 2007)

51% drop in incidence of new blindness
cases in Israel from 33.8 to 16.6 per
100,0002
1999-2003
Annual incidence of
legal blindness per
100,000 inhabitants
aged ≥50 years
40
AMD
Other causes
20
0
1998
2004-2009
Change in annual rate of
blindness due to AMD*
Incidence rate of blindness

*%, adjusted for age and sex
2002
2006
2010
1. Bloch SB, et al. Am J Ophthalmol. 2012;153:209-13
2. Skaat A, et al. Am J Ophthalmol. 2012;153:214-21
Treatment with Lucentis® has helped to reduce
blindness
59% drop in incidence of new wet AMD-related blindness in South East Scotland
Cackett P, et al. Presented at ARVO, 5 May 2013, Seattle, WA
LUMINOUSTM Study:
Largest Observational Trial in Medical Retina
Global, 5-year, multicenter, observational study across all approved indications,
to evaluate the long-term safety, effectiveness, treatment patterns and health
related quality of life outcomes in patients treated with ranibizumab in routine
clinical practice
41 countries - 600 sites - 30,000 patients
Patient recruitment status as of 04 April 2013
Study designed to provide long term safety and
effectiveness data for all licensed indications
5-YEAR, OBSERVATIONAL, NON-INTERVENTIONAL, MULTICENTER, GLOBAL
CLINICAL PRACTICE SETTING
Ranibizumab treatment as per approved local product label:
Neovascular AMD
Visual impairment due to DME
Visual impairment due to macular edema secondary to RVO
Visual impairment due to choroidal neovascularisation secondary to pathologic myopia
First interim analysis:
2,000 patients 1 year
10, 000 patients baseline
Feb 2013
Study start
Mar 2011
YEAR 1
YEAR 2
YEAR 3
Feb 2012
Baseline interim
analysis of first 2,000
patients
Second interim
analysis
Feb 2014
Third interim
analysis
Feb 2015
Final analysis
Feb 2016
YEAR 4
YEAR 5
31 Dec 2013
>20, 000 patients enrolled
End of enrollment
Mar 2015 or
30,000 patients
Mar 2016
End of
study
Comparison of LUMINOUS Treatment Naive wAMD cohort
with key ranibizumab RCTs
CHARACTERISTICS
LUMINOUS
(n=1664)
MARINA
(n=240)
ANCHOR
(n=140)
CATT
(n=301)
IVAN
(n=314)
Age, yrs ; (Mean+ SD)
76.7+9.0
77.0+8.0
76.0+8.6
79.2+7.4
77.8+7.6
Age group (%)
<50 yrs
50-<65
65-<75
75-<85
>85
0.7
9.4
26.75
43.2
20.1
n/a
6.7
26.7
51.7
15
n/a
10
29.3
45.7
15
n/a
n/a
n/a
n/a
n/a
n/a
n/a
n/a
n/a
n/a
Gender, %
Male
Female
39.0
61.0
36.7
63.3
53.6
46.4
39.2
60.8
41.0
59.0
Caucasian, %
91.6
96.7
97.1
98.7
n/a
Mean VA, letters (Mean+
SD)
46.4+24.05
53.7+12.8
47.1+13.2
60.1+14.3
61.8+15.0
CRT, µm; (Mean+ SD)
347.3+126.62
n/a
n/a
247+122
271+129
Predom. Classic, %
35.5
0
96.4
22.5
n/a
OPT12-C007c ;November 2012
wAMD Patients Visual Acuity at 12 months*
Treatment naive
70
5.2+3.3 Treatments 7.4+3.9 Visits
Mean VA letter score (+ SE)
68
Previously Treated (RBZ)
66
5.2+3.3 Treatments 7.5+4.0 Visits
64
62
1463
1393
1247
943
1744
60
132
58
185
56
231
54
52
209
258
50
0
3
6
Months
*Observed Data Set; number of evaluable data points shown above each time interval
9
12
Low rates of ocular serious adverse events
12 month safety analysis
Treatment
Naïve
Category
Ocular SAE of the
primary treated eye
Endophthalmitis
Retinal haemorrhage
Retinal detachment
Ectropion
RPE tear
Uveitis
Visual impairment
N=275
n (%)
Previously
Treated (Other
Previously
Ocular
Treated (RBZ) Treatments)
N=1829
n (%)
N=8
n (%)
Total
N=2112
n (%)
3 (1.1)
8 (0.4)
0
11 (0.5)
1 (0.4)
2 (0.7)
0
0
0
0
0
2 (0.1)
1 (0.1)
2 (0.1)
1 (0.1)
1 (0.1)
1 (0.1)
1 (0.1)
0
0
0
0
0
0
0
3 (0.1)
3 (0.1)
2 (0.1)
1 (0.1)
1 (0.1)
1 (0.1)
1 (0.1)
Low rates of non-ocular SAEs
12 month safety analysis
Preferred term
Previously
Treatment Naïve Treated (RBZ)
N=275, n (%)
N=1829, n (%)
Previously
Treated
(other ocular
treatments)
N=8, n (%)
Total
N=2112
n (%)
Total
13 (4.7)
151 (8.3)
0
164 (7.8)
Fall
Myocardial infarction
Pneumonia
Hip fracture
Atrial fibrillation
Angina pectoris
Cardiac failure congestive
Cerebrovascular accident
0
0
0
0
0
0
0
1 (0.4)
12 (0.7)
12 (0.7)
9 (0.5)
8 (0.4)
7 (0.4)
6 (0.3)
5 (0.3)
4 (0.2)
0
0
0
0
0
0
0
0
12 (0.6)
12 (0.6)
9 (0.4)
8 (0.4)
7 (0.3)
6 (0.3)
5 (0.2
5 (0.2)
Death*
3 (1.1)
33 (1.8)
0
36 (1.7)
*No deaths considered related to study drug; in total 37 patients died, however the end of study CRF record was not completed for one
patient.
Non-ocular SAEs > 0.2% shown
21
Conclusions:
LUMINOUSTM includes patients with more diverse demographics
than in the pivotal trials and is therefore more representative of real
world wAMD, DME and RVO patients
Pre-treatment with ranibizumab was associated with higher baseline
VA and lower CRT at baseline than the treatment naïve group across
all 3 indications
The LUMINOUSTM study further reinforces the well-known safety
profile of ranibizumab in wAMD patients. No new safety signals
observed in this more diverse, co-morbid population
wAMD patients achieved good visual acuity outcomes at 12 months,
irrespective of pre-treatment status, with relatively low numbers of
monitoring visits and injections.
Lucentis® real world data – Overall Conclusions

Real world data for Lucentis® obtained from different
sources confirm the safety and effectiveness of the drug
in the treatment of wet AMD patients

Real world treatment frequency is lower than the
monthly dosing regimen used in the pivotal trials
• 5-6 treatments / year
• Individualized treatment regimen

First data from LUMINOUSTM, a large real world
observational study, further substantiate these findings

Real life utilization data for Lucentis in wAMD

Transcription

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