Statistically Significant Mean VA Gains Through 6 Months2

LUCENTIS is indicated for the treatment of patients with macular edema following retinal vein occlusion (RVO).

Dosing

LUCENTIS 0.5 mg is recommended to be administered by intravitreal injection once a month (approximately 28 days).1

Study design1

In BRAVO, patients with macular edema following branch or hemi-RVO received monthly LUCENTIS 0.3 mg, 0.5 mg intravitreal injections, or monthly sham injections for 6 months. All patients were eligible for macular focal/grid laser treatment beginning at month 3 of the 6-month treatment period.

  • 54% of sham-treated patients received rescue grid laser vs 20% of LUCENTIS-treated patients in the first 6 months. Best corrected visual acuity (BCVA) was measured at a distance of 4 meters (26/131=19.8%; 71/132=53.8%)
In BRAVO and CRUISE, patients received monthly injections of LUCENTIS for 6 months. In spite of being guided by optical coherence tomography and visual acuity retreatment criteria, patients who were then not treated at month 6 experienced, on average, a loss of visual acuity at month 7, whereas patients who were treated at month 6 did not. Patients should be treated monthly.
 
In BRAVO, the primary end point was mean change in BCVA at 6 months2
 
  • In patients with branch retinal vein occlusion (BRVO), LUCENTIS monthly provided a mean gain of 18.3 letters at 6 months compared with 7.3 letters with sham (P<0.01)1,2

MEAN CHANGE IN BCVA FROM BASELINE1,3

BRAVO: Mean Change in BCVA From Baseline

VA, visual acuity.

BRAVO: Select safety through 6 months2,3

SELECT OCULAR ADVERSE EVENTS2,3

ADVERSE EVENTS, % (n) LUCENTIS 0.5 mg (n=130) SHAM (n=131)
Any Intraocular Inflamation Event (Iridocyclitis, Iritis, Vitritis) 0 3.1% (4)
Cataract 3.1% (4) 3.1% (4)
Endophthalmitis 0.8% (1)* 0
Intraocular Pressure Increased 5.4% (7) 1.5% (2)
Iris Neovascularization 0 2.3% (3)
Neovascular Glaucoma 0 0
LUCENTIS 0.5 mg (n=130) SHAM (n=131)
ADVERSE EVENTS, % (n)
Any Intraocular Inflamation Event (Iridocyclitis, Iritis, Vitritis)
0 3.1% (4)
Cataract
3.1% (4) 3.1% (4)
Endophthalmitis
0.8% (1)* 0
Intraocular Pressure Increased
5.4% (7) 1.5% (2)
Iris Neovascularization
0 2.3% (3)
Neovascular Glaucoma
0 0

*Reported as serious.

ANTIPLATELET TRIALISTS' COLLABORATION-DEFINED ARTERIAL THROMBOEMBOLIC EVENTS (APTC-DEFINED ATEs)2,3

ADVERSE EVENTS, % (n) LUCENTIS 0.5 mg (n=130) SHAM (n=131)
Death of Unknown Cause 0 0
Nonfatal Hemorrhagic Stroke 0 0.8% (1)
Nonfatal Ischemic Stroke 0 0
Nonfatal Myocardial Infarction 0.8% (1) 0
Vascular Death 0.8% (1) 0
LUCENTIS 0.5 mg (n=130) SHAM (n=131)
ADVERSE EVENTS, % (n)
Death of Unknown Cause
0 0
Nonfatal Hemorrhagic Stroke
0 0.8% (1)
Nonfatal Ischemic Stroke
0 0
Nonfatal Myocardial Infarction
0.8% (1) 0
Vascular Death
0.8% (1) 0

Reported as fatal hemmorhagic stroke.

MOST COMMON ADVERSE EVENTS OCCURRING IN >10% OF PATIENTS3

ADVERSE EVENTS, % (n) LUCENTIS 0.5 mg (n=130) SHAM (n=131)
Conjunctival Hemorrhage 54.6% (71) 42.0% (55)
Eye Pain 16.2% (21) 14.5% (19)
Maculopathy 10.0% (13) 6.9% (9)
Retinal Depigmentation 10.8% (14) 3.8% (5)
Retinal Exudates 24.6% (32) 13.7% (18)
Retinal Hemorrhage 14.6% (19) 12.2% (16)
Retinal Vascular Disorder 11.5% (15) 6.1% (8)
LUCENTIS 0.5 mg (n=130) SHAM (n=131)
ADVERSE EVENTS, % (n)
Conjunctival Hemorrhage
54.6% (71) 42.0% (55)
Eye Pain
16.2% (21) 14.5% (19)
Maculopathy
10.0% (13) 6.9% (9)
Retinal Depigmentation
10.8% (14) 3.8% (5)
Retinal Exudates
24.6% (32) 13.7% (18)
Retinal Hemorrhage
14.6% (19) 12.2% (16)
Retinal Vascular Disorder
11.5% (15) 6.1% (8)

Additional non-ocular serious adverse events (SAEs) in BRAVO in the LUCENTIS 0.5 mg group reported as potentially associated with systemic vascular endothelial growth factor (VEGF) inhibition included unstable angina (n=1), post-colonoscopy hemorrhage (n=1), and intestinal perforation (n=1).2

  • Reported as serious.2
  • Reported as fatal hemorrhagic stroke.2

Statistically significant mean VA gains through 6 months in patients with macular edema following central RVO4

Study design1

In CRUISE, patients with macular edema following central RVO received monthly LUCENTIS 0.3 or 0.5 mg intravitreal injections or monthly sham injections for 6 months. VA was measured at a distance of 4 meters. 

In CRUISE, the primary end point was mean change in BCVA at 6 months4

CRUISE: Mean Change in BCVA From Baseline

CRUISE: Select safety through 6 months3,4

SELECT OCULAR ADVERSE EVENTS3,4

ADVERSE EVENTS, % (n) LUCENTIS 0.5 mg (n=129) SHAM (n=129)
Any Intraocular Inflammation Event (Iridocyclitis, Iritis, Vitritis) 1.6% (2)§ 3.9% (5)
Cataract 1.6% (2) 0
Endophthalmitis 0 0
Intraocular Pressure Increased 7.8% (10) 3.1% (4)
Iris Neovascularization 0.8% (1)ll 7.0% (9)
Neovascular Glaucoma 0 1.6% (2)
LUCENTIS 0.5 mg (n=129) SHAM (n=129)
ADVERSE EVENTS, % (n)
Any Intraocular Inflammation Event (Iridocyclitis, Iritis, Vitritis)
1.6% (2)§ 3.9% (5)
Cataract
1.6% (2) 0
Endophthalmitis
0 0
Intraocular Pressure Increased
7.8% (10) 3.1% (4)
Iris Neovascularization
0.8% (1)ll 7.0% (9)
Neovascular Glaucoma
0 1.6% (2)

APTC-DEFINED ATEs3,4

ADVERSE EVENTS, % (n) LUCENTIS 0.5 mg (n=129) SHAM (n=129)
Death of Unknown Cause 0 0
Nonfatal Hemorrhagic Stroke 0 0
Nonfatal Ischemic Stroke 0 0
Nonfatal Myocardial Infarction 0.8% (1) 0.8% (1)
Vascular Death 0 0
LUCENTIS 0.5 mg (n=129) SHAM (n=129)
ADVERSE EVENTS, % (n)
Death of Unknown Cause
0 0
Nonfatal Hemorrhagic Stroke
0 0
Nonfatal Ischemic Stroke
0 0
Nonfatal Myocardial Infarction
0.8% (1) 0.8% (1)
Vascular Death
0 0

MOST COMMON ADVERSE EVENTS OCCURRING IN >5% OF PATIENTS3

ADVERSE EVENTS, % (n) LUCENTIS 0.5 mg (n=129) SHAM (n=129)
Conjunctival Hemorrhage 41.1% (53) 32.6% (42)
Eye Irritation 7.0% (9) 4.7% (6)
Eye Pain 18.6% (24) 10.1% (13)
Foreign Body Sensation in Eyes 7.0% (9) 3.9% (5)
Maculopathy 11.6% (15) 7.8% (10)
Nasopharyngitis 5.4% (7) 2.3% (3)
Ocular Vascular Disorder 5.4% (7) 0
Retinal Exudates 17.1% (22) 11.6% (15)
Retinal Hemorrhage 7.8% (10) 10.1% (13)
Retinal Vascular Disorder 13.2% (17) 12.4% (16)
Vitreous Floaters 9.3% (12) 3.9% (5)
Vitreous Hemorrhage 5.4% (7) 7.0% (9)
LUCENTIS 0.5 mg (n=129) SHAM (n=129)
ADVERSE EVENTS, % (n)
Conjunctival Hemorrhage
41.1% (53) 32.6% (42)
Eye Irritation
7.0% (9) 4.7% (6)
Eye Pain
18.6% (24) 10.1% (13)
Foreign Body Sensation in Eyes
7.0% (9) 3.9% (5)
Maculopathy
11.6% (15) 7.8% (10)
Nasopharyngitis
5.4% (7) 2.3% (3)
Ocular Vascular Disorder
5.4% (7) 0
Retinal Exudates
17.1% (22) 11.6% (15)
Retinal Hemorrhage
7.8% (10) 10.1% (13)
Retinal Vascular Disorder
13.2% (17) 12.4% (16)
Vitreous Floaters
9.3% (12) 3.9% (5)
Vitreous Hemorrhage
5.4% (7) 7.0% (9)

Additional non-ocular SAEs in CRUISE in the LUCENTIS 0.5 mg group reported as potentially associated with systemic VEGF inhibition included angina pectoris (n=1) and transient ischemic attack (n=1), which were reported in the same patient.4

  • §The same patient had iritis and vitritis.4 
  • llReported as serious.4

INDICATIONS
Macular edema following retinal vein occlusion (RVO)

LUCENTIS® (ranibizumab injection) is indicated for the treatment of patients with macular edema following retinal vein occlusion (RVO).

Myopic choroidal neovascularization (mCNV)

LUCENTIS® (ranibizumab injection) is indicated for the treatment of patients with myopic choroidal neovascularization (mCNV).

Wet age-related macular degeneration (wAMD)

LUCENTIS® (ranibizumab injection) is indicated for the treatment of patients with neovascular (wet) age-related macular degeneration (wAMD).

Diabetic retinopathy (DR)

LUCENTIS® (ranibizumab injection) is indicated for the treatment of patients with diabetic retinopathy (DR).

Diabetic macular edema (DME)

LUCENTIS® (ranibizumab injection) is indicated for the treatment of patients with diabetic macular edema (DME).

CONTRAINDICATIONS

LUCENTIS is contraindicated in patients with ocular or periocular infections or known hypersensitivity to ranibizumab or any of the excipients in LUCENTIS. Hypersensitivity reactions may manifest as severe intraocular inflammation.

WARNINGS AND PRECAUTIONS

Intravitreal injections, including those with LUCENTIS, have been associated with endophthalmitis, retinal detachment, and iatrogenic traumatic cataract. Proper aseptic injection technique should always be utilized when administering LUCENTIS. Patients should be monitored following the injection to permit early treatment, should an infection occur.

Increases in intraocular pressure (IOP) have been noted both pre-injection and post-injection (at 60 minutes) with LUCENTIS. Monitor intraocular pressure prior to and following intravitreal injection with LUCENTIS and manage appropriately.

Although there was a low rate of arterial thromboembolic events (ATEs) observed in the LUCENTIS clinical trials, there is a potential risk of ATEs following intravitreal use of VEGF inhibitors. ATEs are defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause).

Neovascular (wet) age-related macular degeneration

The ATE rate in the 3 controlled neovascular AMD studies during the first year was 1.9% (17 of 874) in the combined group of patients treated with 0.3 mg or 0.5 mg LUCENTIS compared with 1.1% (5 of 441) in patients from the control arms. In the second year of Studies AMD-1 and AMD-2, the ATE rate was 2.6% (19 of 721) in the combined group of LUCENTIS-treated patients compared with 2.9% (10 of 344) in patients from the control arms. In Study AMD-4, the ATE rates observed in the study during the first year were similar to rates observed in Studies AMD-1, AMD-2, and AMD-3.

In a pooled analysis of 2-year controlled studies (AMD-1, AMD-2, and a study of LUCENTIS used adjunctively with verteporfin photodynamic therapy), the stroke rate (including both ischemic and hemorrhagic stroke) was 2.7% (13 of 484) in patients treated with 0.5 mg LUCENTIS compared to 1.1% (5 of 435) in patients in the control arms (odds ratio 2.2 [95% confidence interval (0.8-7.1)]).

Macular edema following retinal vein occlusion

The ATE rate in the 2 controlled RVO studies during the first 6 months was 0.8% in both the LUCENTIS and control arms of the studies (4 of 525 in the combined group of patients treated with 0.3 mg or 0.5 mg LUCENTIS and 2 of 260 in the control arms). The stroke rate was 0.2% (1 of 525) in the combined group of LUCENTIS-treated patients compared to 0.4% (1 of 260) in the control arms.

Diabetic macular edema and Diabetic Retinopathy

In a pooled analysis of Studies DME-1 and DME-2, the ATE rate at 2 years was 7.2% (18 of 250) with 0.5 mg LUCENTIS, 5.6% (14 of 250) with 0.3 mg LUCENTIS, and 5.2% (13 of 250) with control. The stroke rate at 2 years was 3.2% (8 of 250) with 0.5 mg LUCENTIS, 1.2% (3 of 250) with 0.3 mg LUCENTIS, and 1.6% (4 of 250) with control. At 3 years, the ATE rate was 10.4% (26 of 249) with 0.5 mg LUCENTIS and 10.8% (27 of 250) with 0.3 mg LUCENTIS; the stroke rate was 4.8% (12 of 249) with 0.5 mg LUCENTIS and 2.0% (5 of 250) with 0.3 mg LUCENTIS.

Fatal events occurred more frequently in patients with DME and DR at baseline treated monthly with LUCENTIS compared with control. A pooled analysis of Studies D-1 and D-2, showed that fatalities in the first 2 years occurred in 4.4% (11 of 250) of patients treated with 0.5 mg LUCENTIS, in 2.8% (7 of 250) of patients treated with 0.3 mg LUCENTIS, and in 1.2% (3 of 250) of control patients. Over 3 years, fatalities occurred in 6.4% (16 of 249) of patients treated with 0.5 mg LUCENTIS and in 4.4% (11 of 250) of patients treated with 0.3 mg LUCENTIS. Although the rate of fatal events was low and included causes of death typical of patients with advanced diabetic complications, a potential relationship between these events and intravitreal use of VEGF inhibitors cannot be excluded.

ADVERSE EVENTS

Serious adverse events related to the injection procedure that occurred in <0.1% of intravitreal injections included endophthalmitis, rhegmatogenous retinal detachment, and iatrogenic traumatic cataract.

In the LUCENTIS Phase III clinical trials, the most common ocular side effects included conjunctival hemorrhage, eye pain, vitreous floaters, and increased intraocular pressure. The most common non-ocular side effects included nasopharyngitis, anemia, nausea, and cough.

As with all therapeutic proteins, there is the potential for an immune response in patients treated with LUCENTIS. The clinical significance of immunoreactivity to LUCENTIS is unclear at this time.

FOR ADDITIONAL SAFETY INFORMATION, PLEASE SEE LUCENTIS FULL PRESCRIBING INFORMATION.

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at (888) 835-2555.

    • LUCENTIS [package insert]. South San Francisco, CA: Genentech, Inc; 2018.

      LUCENTIS [package insert]. South San Francisco, CA: Genentech, Inc; 2018.

    • Campochiaro PA, et al; BRAVO Investigators. Ophthalmology. 2010;117:1102-1112.

      Campochiaro PA, et al; BRAVO Investigators. Ophthalmology. 2010;117:1102-1112.

    • Data on file. South San Francisco, CA: Genentech, Inc.

      Data on file. South San Francisco, CA: Genentech, Inc.

    • Brown DM, et al; CRUISE Investigators. Ophthalmology. 2010;117:1124-1133.

       

      Brown DM, et al; CRUISE Investigators. Ophthalmology. 2010;117:1124-1133.