LUCENTIS
Generic: RANIBIZUMAB
Basic Information
Manufacturer
Genentech, Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
INTRAVITREAL
FDA Set ID
de4e66cc-ca05-4dc9-8262-e00e9b41c36d
Indications & Usage
1 INDICATIONS AND USAGE LUCENTIS is indicated for the treatment of patients with: LUCENTIS, a vascular endothelial growth factor (VEGF) inhibitor, is indicated for the treatment of patients with: Neovascular (Wet) Age-Related Macular Degeneration (AMD) ( 1.1 ) Macular Edema Following Retinal Vein Occlusion (RVO) ( 1.2 ) Diabetic Macular Edema (DME) ( 1.3 ) Diabetic Retinopathy (DR) ( 1.4 ) Myopic Choroidal Neovascularization (mCNV) ( 1.5 ) 1.1 Neovascular (Wet) Age-Related Macular Degeneration (AMD) 1.2 Macular Edema Following Retinal Vein Occlusion (RVO) 1.3 Diabetic Macular Edema (DME) 1.4 Diabetic Retinopathy (DR) 1.5 Myopic Choroidal Neovascularization (mCNV)
Adverse Reactions
6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the label: Endophthalmitis and Retinal Detachments [see Warnings and Precautions (5.1) ] Increases in Intraocular Pressure [see Warnings and Precautions (5.2) ] Thromboembolic Events [see Warnings and Precautions (5.3) ] Fatal Events in patients with DME and DR at baseline [see Warnings and Precautions (5.4) ] The most common adverse reactions (reported more frequently in LUCENTIS-treated subjects than control subjects) are conjunctival hemorrhage, eye pain, vitreous floaters, and increased IOP ( 6.2 ).
To report SUSPECTED ADVERSE REACTIONS, contact Genentech at 1-888-835-2555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Injection Procedure Serious adverse reactions related to the injection procedure have occurred in < 0.1% of intravitreal injections, including endophthalmitis [see Warnings and Precautions (5.1) ] , rhegmatogenous retinal detachment, and iatrogenic traumatic cataract.
6.2 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The data below reflect exposure to 0.5 mg LUCENTIS in 440 patients with neovascular AMD in Studies AMD-1, AMD-2, and AMD-3; in 259 patients with macular edema following RVO.
The data also reflect exposure to 0.3 mg LUCENTIS in 250 patients with DME and DR at baseline [see Clinical Studies (14) ] .
Safety data observed in 224 patients with mCNV, as well as Studies AMD-4 and D-3, were consistent with these results.
On average, the rates and types of adverse reactions in patients were not significantly affected by dosing regimen.
Ocular Reactions Table 1 shows frequently reported ocular adverse reactions in LUCENTIS-treated patients compared with the control group.
Table 1 Ocular Reactions in the DME and DR, AMD, and RVO Studies DME and DR 2-year AMD 2-year AMD 1-year RVO 6-month Adverse Reaction LUCENTIS 0.3 mg Control LUCENTIS 0.5 mg Control LUCENTIS 0.5 mg Control LUCENTIS 0.5 mg Control n=250 n=250 n=379 n=379 n=440 n=441 n=259 n=260 Conjunctival hemorrhage 47% 32% 74% 60% 64% 50% 48% 37% Eye pain 17% 13% 35% 30% 26% 20% 17% 12% Vitreous floaters 10% 4% 27% 8% 19% 5% 7% 2% Intraocular pressure increased 18% 7% 24% 7% 17% 5% 7% 2% Vitreous detachment 11% 15% 21% 19% 15% 15% 4% 2% Intraocular inflammation 4% 3% 18% 8% 13% 7% 1% 3% Cataract 28% 32% 17% 14% 11% 9% 2% 2% Foreign body sensation in eyes 10% 5% 16% 14% 13% 10% 7% 5% Eye irritation 8% 5% 15% 15% 13% 12% 7% 6% Lacrimation increased 5% 4% 14% 12% 8% 8% 2% 3% Blepharitis 3% 2% 12% 8% 8% 5% 0% 1% Dry eye 5% 3% 12% 7% 7% 7% 3% 3% Visual disturbance or vision blurred 8% 4% 18% 15% 13% 10% 5% 3% Eye pruritis 4% 4% 12% 11% 9% 7% 1% 2% Ocular hyperemia 9% 9% 11% 8% 7% 4% 5% 3% Retinal disorder 2% 2% 10% 7% 8% 4% 2% 1% Maculopathy 5% 7% 9% 9% 6% 6% 11% 7% Retinal degeneration 1% 0% 8% 6% 5% 3% 1% 0% Ocular discomfort 2% 1% 7% 4% 5% 2% 2% 2% Conjunctival hyperemia 1% 2% 7% 6% 5% 4% 0% 0% Posterior capsule opacification 4% 3% 7% 4% 2% 2% 0% 1% Injection site hemorrhage 1% 0% 5% 2% 3% 1% 0% 0% Non-Ocular Reactions Non-ocular adverse reactions with an incidence of ≥ 5% in patients receiving LUCENTIS for DR, DME, AMD, and/or RVO and which occurred at a ≥ 1% higher frequency in patients treated with LUCENTIS compared to control are shown in Table 2 .
Though less common, wound healing complications were also observed in some studies.
Table 2 Non-Ocular Reactions in the DME and DR, AMD, and RVO Studies DME and DR 2-year AMD 2-year AMD 1-year RVO 6-month Adverse Reaction LUCENTIS 0.3 mg Control LUCENTIS 0.5 mg Control LUCENTIS 0.5 mg Control LUCENTIS 0.5 mg Control n=250 n=250 n=379 n=379 n=440 n=441 n=259 n=260 Nasopharyngitis 12% 6% 16% 13% 8% 9% 5% 4% Anemia 11% 10% 8% 7% 4% 3% 1% 1% Nausea 10% 9% 9% 6% 5% 5% 1% 2% Cough 9% 4% 9% 8% 5% 4% 1% 2% Constipation 8% 4% 5% 7% 3% 4% 0% 1% Seasonal allergy 8% 4% 4% 4% 2% 2% 0% 2% Hypercholesterolemia 7% 5% 5% 5% 3% 2% 1% 1% Influenza 7% 3% 7% 5% 3% 2% 3% 2% Renal failure 7% 6% 1% 1% 0% 0% 0% 0% Upper respiratory tract infection 7% 7% 9% 8% 5% 5% 2% 2% Gastroesophageal reflux disease 6% 4% 4% 6% 3% 4% 1% 0% Headache 6% 8% 12% 9% 6% 5% 3% 3% Edema peripheral 6% 4% 3% 5% 2% 3% 0% 1% Renal failure chronic 6% 2% 0% 1% 0% 0% 0% 0% Neuropathy peripheral 5% 3% 1% 1% 1% 0% 0% 0% Sinusitis 5% 8% 8% 7% 5% 5% 3% 2% Bronchitis 4% 4% 11% 9% 6% 5% 0% 2% Atrial fibrillation 3% 3% 5% 4% 2% 2% 1% 0% Arthralgia 3% 3% 11% 9% 5% 5% 2% 1% Chronic obstructive pulmonary disease 1% 1% 6% 3% 3% 1% 0% 0% Wound healing complications 1% 0% 1% 1% 1% 0% 0% 0% 6.3 Immunogenicity As with all therapeutic proteins, there is the potential for an immune response in patients treated with LUCENTIS.
The immunogenicity data reflect the percentage of patients whose test results were considered positive for antibodies to LUCENTIS in immunoassays and are highly dependent on the sensitivity and specificity of the assays.
The pre-treatment incidence of immunoreactivity to LUCENTIS was 0%-5% across treatment groups.
After monthly dosing with LUCENTIS for 6 to 24 months, antibodies to LUCENTIS were detected in approximately 1%-9% of patients.
The clinical significance of immunoreactivity to LUCENTIS is unclear at this time.
Among neovascular AMD patients with the highest levels of immunoreactivity, some were noted to have iritis or vitritis.
Intraocular inflammation was not observed in patients with DME and DR at baseline, or RVO patients with the highest levels of immunoreactivity.
6.4 Postmarketing Experience The following adverse reaction has been identified during post-approval use of LUCENTIS.
Because this reaction was reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate the frequency or establish a causal relationship to drug exposure.
Ocular: Tear of retinal pigment epithelium among patients with neovascular AMD
To report SUSPECTED ADVERSE REACTIONS, contact Genentech at 1-888-835-2555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Injection Procedure Serious adverse reactions related to the injection procedure have occurred in < 0.1% of intravitreal injections, including endophthalmitis [see Warnings and Precautions (5.1) ] , rhegmatogenous retinal detachment, and iatrogenic traumatic cataract.
6.2 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The data below reflect exposure to 0.5 mg LUCENTIS in 440 patients with neovascular AMD in Studies AMD-1, AMD-2, and AMD-3; in 259 patients with macular edema following RVO.
The data also reflect exposure to 0.3 mg LUCENTIS in 250 patients with DME and DR at baseline [see Clinical Studies (14) ] .
Safety data observed in 224 patients with mCNV, as well as Studies AMD-4 and D-3, were consistent with these results.
On average, the rates and types of adverse reactions in patients were not significantly affected by dosing regimen.
Ocular Reactions Table 1 shows frequently reported ocular adverse reactions in LUCENTIS-treated patients compared with the control group.
Table 1 Ocular Reactions in the DME and DR, AMD, and RVO Studies DME and DR 2-year AMD 2-year AMD 1-year RVO 6-month Adverse Reaction LUCENTIS 0.3 mg Control LUCENTIS 0.5 mg Control LUCENTIS 0.5 mg Control LUCENTIS 0.5 mg Control n=250 n=250 n=379 n=379 n=440 n=441 n=259 n=260 Conjunctival hemorrhage 47% 32% 74% 60% 64% 50% 48% 37% Eye pain 17% 13% 35% 30% 26% 20% 17% 12% Vitreous floaters 10% 4% 27% 8% 19% 5% 7% 2% Intraocular pressure increased 18% 7% 24% 7% 17% 5% 7% 2% Vitreous detachment 11% 15% 21% 19% 15% 15% 4% 2% Intraocular inflammation 4% 3% 18% 8% 13% 7% 1% 3% Cataract 28% 32% 17% 14% 11% 9% 2% 2% Foreign body sensation in eyes 10% 5% 16% 14% 13% 10% 7% 5% Eye irritation 8% 5% 15% 15% 13% 12% 7% 6% Lacrimation increased 5% 4% 14% 12% 8% 8% 2% 3% Blepharitis 3% 2% 12% 8% 8% 5% 0% 1% Dry eye 5% 3% 12% 7% 7% 7% 3% 3% Visual disturbance or vision blurred 8% 4% 18% 15% 13% 10% 5% 3% Eye pruritis 4% 4% 12% 11% 9% 7% 1% 2% Ocular hyperemia 9% 9% 11% 8% 7% 4% 5% 3% Retinal disorder 2% 2% 10% 7% 8% 4% 2% 1% Maculopathy 5% 7% 9% 9% 6% 6% 11% 7% Retinal degeneration 1% 0% 8% 6% 5% 3% 1% 0% Ocular discomfort 2% 1% 7% 4% 5% 2% 2% 2% Conjunctival hyperemia 1% 2% 7% 6% 5% 4% 0% 0% Posterior capsule opacification 4% 3% 7% 4% 2% 2% 0% 1% Injection site hemorrhage 1% 0% 5% 2% 3% 1% 0% 0% Non-Ocular Reactions Non-ocular adverse reactions with an incidence of ≥ 5% in patients receiving LUCENTIS for DR, DME, AMD, and/or RVO and which occurred at a ≥ 1% higher frequency in patients treated with LUCENTIS compared to control are shown in Table 2 .
Though less common, wound healing complications were also observed in some studies.
Table 2 Non-Ocular Reactions in the DME and DR, AMD, and RVO Studies DME and DR 2-year AMD 2-year AMD 1-year RVO 6-month Adverse Reaction LUCENTIS 0.3 mg Control LUCENTIS 0.5 mg Control LUCENTIS 0.5 mg Control LUCENTIS 0.5 mg Control n=250 n=250 n=379 n=379 n=440 n=441 n=259 n=260 Nasopharyngitis 12% 6% 16% 13% 8% 9% 5% 4% Anemia 11% 10% 8% 7% 4% 3% 1% 1% Nausea 10% 9% 9% 6% 5% 5% 1% 2% Cough 9% 4% 9% 8% 5% 4% 1% 2% Constipation 8% 4% 5% 7% 3% 4% 0% 1% Seasonal allergy 8% 4% 4% 4% 2% 2% 0% 2% Hypercholesterolemia 7% 5% 5% 5% 3% 2% 1% 1% Influenza 7% 3% 7% 5% 3% 2% 3% 2% Renal failure 7% 6% 1% 1% 0% 0% 0% 0% Upper respiratory tract infection 7% 7% 9% 8% 5% 5% 2% 2% Gastroesophageal reflux disease 6% 4% 4% 6% 3% 4% 1% 0% Headache 6% 8% 12% 9% 6% 5% 3% 3% Edema peripheral 6% 4% 3% 5% 2% 3% 0% 1% Renal failure chronic 6% 2% 0% 1% 0% 0% 0% 0% Neuropathy peripheral 5% 3% 1% 1% 1% 0% 0% 0% Sinusitis 5% 8% 8% 7% 5% 5% 3% 2% Bronchitis 4% 4% 11% 9% 6% 5% 0% 2% Atrial fibrillation 3% 3% 5% 4% 2% 2% 1% 0% Arthralgia 3% 3% 11% 9% 5% 5% 2% 1% Chronic obstructive pulmonary disease 1% 1% 6% 3% 3% 1% 0% 0% Wound healing complications 1% 0% 1% 1% 1% 0% 0% 0% 6.3 Immunogenicity As with all therapeutic proteins, there is the potential for an immune response in patients treated with LUCENTIS.
The immunogenicity data reflect the percentage of patients whose test results were considered positive for antibodies to LUCENTIS in immunoassays and are highly dependent on the sensitivity and specificity of the assays.
The pre-treatment incidence of immunoreactivity to LUCENTIS was 0%-5% across treatment groups.
After monthly dosing with LUCENTIS for 6 to 24 months, antibodies to LUCENTIS were detected in approximately 1%-9% of patients.
The clinical significance of immunoreactivity to LUCENTIS is unclear at this time.
Among neovascular AMD patients with the highest levels of immunoreactivity, some were noted to have iritis or vitritis.
Intraocular inflammation was not observed in patients with DME and DR at baseline, or RVO patients with the highest levels of immunoreactivity.
6.4 Postmarketing Experience The following adverse reaction has been identified during post-approval use of LUCENTIS.
Because this reaction was reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate the frequency or establish a causal relationship to drug exposure.
Ocular: Tear of retinal pigment epithelium among patients with neovascular AMD