Cimerli Drug Information
Generic name: RANIBIZUMAB-EQRN
Vascular Endothelial Growth Factor Inhibitor [EPC]
Uses of Cimerli
Neovascular (Wet) Age-Related Macular Degeneration (AMD)
Macular Edema Following Retinal Vein Occlusion (RVO)
Diabetic Macular Edema (DME)
Diabetic Retinopathy (DR)
Myopic Choroidal
Neovascularization (mCNV)
Dosage & Administration of Cimerli
General Dosing Information FOR OPHTHALMIC INTRAVITREAL INJECTION. Vials: A 5-micron sterile filter needle (19-gauge × 1-1/2 inch), a 1-mL Luer lock syringe and a 30-gauge × 1/2 inch sterile injection needle are needed but not included.
Neovascular (Wet) Age-Related Macular Degeneration (AMD) CIMERLI 0.5 mg (0.05 mL of 10 mg/mL solution) is recommended to be administered by intravitreal injection once a month (approximately 28 days). Although not as effective, patients may be treated with 3 monthly doses followed by less frequent dosing with regular assessment. In the 9 months after three initial monthly doses, less frequent dosing with 4-5 doses on average is expected to maintain visual acuity while monthly dosing may be expected to result in an additional average 1-2 letter gain.
Patients should be assessed regularly. Although not as effective, patients may also be treated with one dose every 3 months after 4 monthly doses. Compared with continued monthly dosing, dosing every 3 months over the next 9 months will lead to an approximate 5-letter (1-line) loss of visual acuity benefit, on average.
In Studies RVO-1 and RVO-2, patients received monthly injections of ranibizumab for 6 months. In spite of being guided by optical coherence tomography and visual acuity re-treatment 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 may be retreated if needed.
Preparation for Administration Vial
Using aseptic technique, all of the CIMERLI vial contents are withdrawn through a 5-micron (19-gauge × 1-1/2 inch), sterile filter needle attached to a 1 mL syringe (not included). The filter needle should be discarded after withdrawal of the vial contents and should not be used for intravitreal injection. The filter needle should be replaced with a sterile 30-gauge × 1/2 inch needle for the intravitreal injection.
Use aseptic technique to carry out the following preparation steps: 1. Prepare for intravitreal injection with the following medical devices for use in a single eye (not included): • a 5-micron sterile filter needle (19-gauge × 1-1/2 inch) • a 1 mL sterile Luer lock syringe (with marking to measure 0.05 mL) • a sterile injection needle (30-gauge × 1/2-inch) 2. Before withdrawal, disinfect the outer part of the rubber stopper of the vial. 3.
Place a 5-micron filter needle (19-gauge × 1-1/2 inch) onto a 1 mL Luer lock syringe using aseptic technique. 4. Push the filter needle into the center of the vial stopper until the needle touches the bottom edge of the vial. 5. Withdraw all the liquid from the vial, keeping the vial in an upright position, slightly inclined to ease complete withdrawal. 6.
Ensure that the plunger rod is drawn sufficiently back when emptying the vial in order to completely empty the filter needle. 7. Attach a 30-gauge × 1/2-inch sterile injection needle firmly onto the syringe by screwing it tightly onto the Luer lock. Carefully remove the needle cap by pulling it straight off.
Do not wipe the needle at any time. 9. Hold the syringe with the needle pointing up. If there are any air bubbles, gently tap the syringe with your finger until the bubbles rise to the top. 10.
Hold the syringe at eye level, and carefully push the plunger rod until the plunger tip is aligned with the line that marks 0.05 mL on the syringe. Image Image Image Image Image
Administration
The intravitreal injection procedure should be carried out under controlled aseptic conditions, which include the use of sterile gloves, a sterile drape, and a sterile eyelid speculum (or equivalent). Adequate anesthesia and a broad-spectrum microbicide should be given prior to the injection. Prior to and 30 minutes following the intravitreal injection, patients should be monitored for elevation in intraocular pressure using tonometry.
Monitoring may also consist of a check for perfusion of the optic nerve head immediately after the injection. Patients should also be monitored for and instructed to report any symptoms suggestive of endophthalmitis without delay following the injection. Each vial should only be used for the treatment of a single eye.
If the contralateral eye requires treatment, a new vial should be used and the sterile field, syringe, gloves, drapes, eyelid speculum, filter needle, and injection needles should be changed before CIMERLI is administered to the other eye. No special dosage modification is required for any of the populations that have been studied (e.g., gender, elderly).
Side Effects of Cimerli
Injection Procedure
Serious adverse reactions related to the injection procedure have occurred in < 0.1% of intravitreal injections, including endophthalmitis, rhegmatogenous retinal detachment, and iatrogenic traumatic cataract.
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 ranibizumab 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 ranibizumab in 250 patients with DME and DR at baseline.
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 ranibizumab-treated patients compared with the control group.
Table 1 Ocular Reactions in the DME and DR, AMD, and RVO Studies Non-Ocular Reactions Non-ocular adverse reactions with an incidence of ≥ 5% in patients receiving ranibizumab for DR, DME, AMD, and/or RVO and which occurred at a ≥ 1% higher frequency in patients treated with ranibizumab compared to control are shown in Table 2. Though less common, wound healing complications were also observed in some studies.
Immunogenicity
The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of ranibizumab or of other ranibizumab products. The pre-treatment incidence of immunoreactivity to ranibizumab was 0%-5% across treatment groups.
After monthly dosing with ranibizumab for 6 to 24 months, antibodies to ranibizumab were detected in approximately 1%-9% of patients. The clinical significance of immunoreactivity to ranibizumab products 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.
Postmarketing Experience
The following adverse reaction has been identified during post-approval use of ranibizumab products. 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
| Adverse Reaction | DME and DR 2-year | AMD 2-year | AMD 1-year | RVO 6-month | ||||
|---|---|---|---|---|---|---|---|---|
| Ranibizumab 0.3 mg | Control | Ranibizumab 0.5 mg | Control | Ranibizumab 0.5 mg | Control | Ranibizumab 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% |
| Adverse Reaction | DME and DR 2-year | AMD 2-year | AMD 1-year | RVO 6-month | ||||
|---|---|---|---|---|---|---|---|---|
| Ranibizumab 0.3 mg | Control | Ranibizumab 0.5 mg | Control | Ranibizumab 0.5 mg | Control | Ranibizumab 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% |
Warnings & Cautions for Cimerli
Endophthalmitis and Retinal Detachments
Intravitreal injections, including those with ranibizumab products, have been associated with endophthalmitis and retinal detachments. Proper aseptic injection technique should always be used when administering CIMERLI. In addition, patients should be monitored following the injection to permit early treatment should an infection occur.
Increases in Intraocular Pressure Increases in intraocular pressure have been noted both pre-injection and post-injection (at 60 minutes) while being treated with ranibizumab products. Monitor intraocular pressure prior to and following intravitreal injection with CIMERLI and manage appropriately.
Thromboembolic Events
Although there was a low rate of arterial thromboembolic events (ATEs) observed in the ranibizumab clinical trials, there is a potential risk of ATEs following intravitreal use of VEGF inhibitors. Arterial thromboembolic events are defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause). In Study AMD-4, the ATE rates observed in the 0.5 mg arms during the first and second year were similar to rates observed in Studies AMD-1, AMD-2, and AMD-3.
Diabetic Macular Edema and Diabetic Retinopathy Safety data are derived from studies D-1 and D-2. All enrolled patients had DME and DR at baseline. At 3 years, the ATE rate was mg ranibizumab and mg ranibizumab; the stroke rate was mg ranibizumab and mg ranibizumab.
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.
Retinal Vasculitis with or without Occlusion
Retinal vasculitis with or without occlusion, typically in the presence of preexisting intraocular inflammation or post-treatment with other intravitreal agents, have been reported with the use of ranibizumab products. Discontinue treatment with CIMERLI in patients who develop these events. Patients should be instructed to report any change in vision without delay.
Drug Interactions with Cimerli
Drug interaction studies have not been conducted with ranibizumab products. Ranibizumab intravitreal injection has been used adjunctively with PDT.
Pregnancy Safety for Cimerli
Pregnancy Risk Summary There are no adequate and well-controlled studies of ranibizumab products administered in pregnant women. Administration of ranibizumab to pregnant monkeys throughout the period of organogenesis resulted in a low incidence of skeletal abnormalities at intravitreal doses 13-times the predicted human exposure (based on maximal serum trough levels ) after a single eye treatment at the recommended clinical dose. No skeletal abnormalities were observed at serum trough levels equivalent to the predicted human exposure after a single eye treatment at the recommended clinical dose.
Animal reproduction studies are not always predictive of human response, and it is not known whether ranibizumab products can cause fetal harm when administered to a pregnant woman. Based on the anti-VEGF mechanism of action for ranibizumab products, treatment with ranibizumab products may pose a risk to human embryofetal development. CIMERLI should be given to a pregnant woman only if clearly needed.
Data Animal Data An embryo-fetal developmental toxicity study was performed on pregnant cynomolgus monkeys. Skeletal abnormalities including incomplete and/or irregular ossification of bones in the skull, vertebral column, and hindlimbs and shortened supernumerary ribs were seen at a low incidence in fetuses from animals treated with 1 mg/eye of ranibizumab. The 1 mg/eye dose resulted in trough serum ranibizumab levels up to 13 times higher than predicted C max levels with single eye treatment in humans.
No skeletal abnormalities were seen at the lower dose of 0.125 mg/eye, a dose which resulted in trough exposures equivalent to single eye treatment in humans. No effect on the weight or structure of the placenta, maternal toxicity, or embryotoxicity was observed.
Pediatric Use of Cimerli
Pediatric Use The safety and effectiveness of CIMERLI in pediatric patients have not been established.
Contraindications for Cimerli
Ocular or Periocular Infections CIMERLI is contraindicated in patients with ocular or periocular infections.
Hypersensitivity CIMERLI is contraindicated in patients with known hypersensitivity to ranibizumab products or any of the excipients in CIMERLI. Hypersensitivity reactions may manifest as severe intraocular inflammation.
Overdosage Information for Cimerli
More concentrated doses as high as 2 mg ranibizumab in 0.05 mL have been administered to patients. No additional unexpected adverse reactions were seen.
Clinical Studies of Cimerli
Neovascular (Wet) Age-Related Macular Degeneration (AMD)
The safety and efficacy of ranibizumab were assessed in three randomized, double-masked, sham- or active-controlled studies in patients with neovascular AMD. A total of 1323 patients (ranibizumab 879, control 444) were enrolled in the three studies. Studies AMD-1 and AMD-2 In Study AMD-1, patients with minimally classic or occult (without classic) CNV lesions received monthly ranibizumab 0.3 mg or 0.5 mg intravitreal injections or monthly sham injections.
Data are available through Month 24. In Study AMD-2, patients with predominantly classic CNV lesions received one of the following: 1 monthly ranibizumab 0.3 mg intravitreal injections and sham PDT; 2 monthly ranibizumab 0.5 mg intravitreal injections and sham PDT; or 3 sham intravitreal injections and active PDT. Sham PDT (or active PDT) was given with the initial ranibizumab (or sham) intravitreal injection and every 3 months thereafter if FA showed persistence or recurrence of leakage.
In both studies, the primary efficacy endpoint was the proportion of patients who maintained vision, defined as losing fewer than 15 letters of visual acuity at 12 months compared with baseline. Almost all ranibizumab-treated patients (approximately 95%) maintained their visual acuity. The size of the lesion did not significantly affect the results.
Detailed results are shown in Table 3, Table 4, and Figure 1 below. At Month 12, the mean change in the total area of the CNV lesion was 0.1-0.3 disc areas (DA) for ranibizumab versus 2.3-2.6 DA for the control arms. At Month 24, the mean change in the total area of the CNV lesion was 0.3-0.4 DA for ranibizumab versus 2.9-3.1 DA for the control arms.
Figure 1 Study AMD-3 Study AMD-3 was a randomized, double-masked, sham-controlled, 2-year study designed to assess the safety and efficacy of ranibizumab in patients with neovascular AMD (with or without a classic CNV component). Data are available through Month 12. Patients treated with ranibizumab in Study AMD-3 received a mean of six total treatments out of a possible 6 from Day 0 through Month 12.
In Study AMD-3, the primary efficacy endpoint was the mean change in visual acuity at 12 months compared with baseline (see Figure 2). After an initial increase in visual acuity (following monthly dosing), on average, patients dosed once every 3 months with ranibizumab lost visual acuity, returning to baseline at Month 12. In Study AMD-3, almost all ranibizumab-treated patients (90%) lost fewer than 15 letters of visual acuity at Month 12.
Figure 2 Mean Change in Visual Acuity from Baseline to Month 12 in Study AMD-3 Figure 2 Study AMD-4 Study AMD-4 was a randomized, double-masked, active treatment-controlled, two-year study designed to assess the safety and efficacy of ranibizumab 0.5 mg administered monthly or less frequently than monthly in patients with neovascular AMD. Patients randomized to the ranibizumab 0.5 mg less frequent dosing arm received three monthly doses followed by monthly assessments where patients were eligible to receive ranibizumab injections guided by pre-specified re-treatment criteria. The distribution of injections received in the less frequent dosing arm is shown in Figure 4.
Figure 3 Figure 4
Macular Edema Following Retinal Vein Occlusion (RVO)
The safety and efficacy of ranibizumab were assessed in two randomized, double-masked, 1-year studies in patients with macular edema following RVO. Sham controlled data are available through Month 6. Patient age ranged from 20 to 91 years, with a mean age of 67 years.
All patients completing Month 6 were eligible to receive ranibizumab injections guided by pre-specified re-treatment criteria until the end of the studies at Month 12. In Study RVO-1, patients with macular edema following branch or hemi-RVO, received monthly ranibizumab 0.3 mg or 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.
At Month 6, after monthly treatment with 0.5 mg ranibizumab, the following clinical results were observed: Table 5 Visual Acuity Outcomes at Figure 5
Diabetic Macular Edema (DME) Efficacy and safety data of ranibizumab are derived from studies D-1 and D-2. All enrolled patients had DR and DME at baseline. The studies were sham-controlled through Month 24.
Patient age ranged from 21 to 91 years, with a mean age of 62 years. In Studies D-1 and D-2, patients received monthly ranibizumab 0.3 mg or 0.5 mg intravitreal injections or monthly sham injections during the 24-month controlled treatment period. Compared to monthly ranibizumab 0.3 mg, no additional benefit was observed with monthly treatment with ranibizumab 0.5 mg.
Patients in the sham arms who received ranibizumab 0.5 mg beginning at Month 25 achieved lesser VA gains compared to patients who began treatment with ranibizumab at the beginning of the studies. In Studies D-1 and D-2, patients received monthly injections of ranibizumab for 12 or 36 months, after which 500 patients opted to continue in the long-term follow-up study. The remaining 202 patients were followed for less than 12 months.
Figure 6
Diabetic Retinopathy (DR) Efficacy and safety data of ranibizumab are derived from Studies D-1 and D-2 and D-3. Study D-3 enrolled DR patients both with and without DME at baseline. Of the 759 patients enrolled in Studies D-1 and D-2, 746 patients had a baseline assessment of fundus photography.
Patients had baseline Early Treatment Diabetic Retinopathy Study Diabetic Retinopathy Severity Scores (ETDRS-DRSS) ranging from 10 to 75. The ETDRS-DRSS could not be graded in 5% of patients at baseline, and 2% of patients had absent or questionable DR at baseline. Approximately 20% of the overall population had prior PRP.
After monthly treatment with ranibizumab 0.3 mg, the following clinical results were observed (Table 7; Figure 7): Table 7 ≥3-Step and ≥2-Step Improvement at, DR improvement by ≥3-steps in ETDRS-DRSS from baseline in subgroups examined (e.g., age, gender, race, baseline visual acuity, baseline HbA1c, prior DME therapy at baseline, baseline DR severity (NPDR, PDR)) were generally consistent with the results in the overall population. The difference in the proportion of patients treated with ranibizumab 0.3 mg compared to sham who achieved DR improvement based on the ETDRS-DRSS was observed as early as Study D-3 enrolled DR patients with and without DME; 88 (22%) eyes with baseline DME and 306 (78%) eyes without baseline DME and balanced across treatment groups. Study D-3 was a randomized, active-controlled study where patient age ranged from 20 to 83 with a mean age of 51 years.
All eyes in the ranibizumab group received a baseline 0.5 mg intravitreal injection followed by 3 monthly intravitreal injections, after which treatment was guided by pre-specified retreatment criteria. Patients had baseline ETDRS-DRSS ranging from 20 to 85. An analysis of data from Study D-3 demonstrated that at Year 2 in the ranibizumab group, 31.7% and 28.4% of eyes in the subgroups with baseline DME and without baseline DME, respectively, had ≥ 3-step improvement from baseline in ETDRS-DRSS.
Table 8 Proportion of Eyes with ≥ 3-Step and ≥ 2-Step Improvement from Baseline in ETDRS-DRSS at Year 2 in Study D-3 Myopic Choroidal Neovascularization (mCNV) The efficacy and safety data of ranibizumab were assessed in a randomized, double-masked, active-controlled 3-month study in patients with mCNV. Patients age ranged from 18 to 87 years, with a mean age of 55 years. A total of 276 patients (222 patients in the ranibizumab treated Groups I and II; 55 patients in the active control PDT group) were enrolled.
Patients randomized to the ranibizumab groups received injections guided by prespecified re-treatment criteria. The retreatment criteria in Group I were vision stability guided, with the Best Corrected Visual Acuity (BCVA) at the current visit being assessed for changes compared with the two preceding monthly BCVA values. The retreatment criteria in Group II were disease activity guided, based on BCVA decrease from the previous visit that was attributable to intra- or sub-retinal fluid or active leakage secondary to mCNV as assessed by OCT and/or FA compared to the previous monthly visit.
Visual gains for the two ranibizumab 0.5 mg treatment arms were superior to the active control arm. Efficacy was comparable between Group I and Group II. Figure 9
| Outcome Measure | Month | Sham n=229 | Ranibizumab 0.5 mg n=230 | Estimated Difference (95% CI) Adjusted estimate based on the stratified model; p < 0.01 |
|---|---|---|---|---|
| Loss of <15 letters in visual acuity (%) | 12 | 60% | 91% | 30% (23%, 37%) |
| 24 | 56% | 89% | 33% (26%, 41%) | |
| Gain of ≥15 letters in visual acuity (%) | 12 | 6% | 31% | 25% (18%, 31%) |
| 24 | 4% | 30% | 25% (18%, 31%) | |
| Mean change in visual acuity (letters) (SD) | 12 | −11.0 (17.9) | +6.3 ( 14.1) | 17.1 (14.2, 20.0) |
| 24 | −15.0 (19.7) | +5.5 ( 15.9) | 20.1 (16.9, 23.4) |
| Outcome Measure | Month | PDT n=141 | Ranibizumab 0.5 mg n=139 | Estimated Difference (95% CI) Adjusted estimate based on the stratified model; p < 0.01 |
|---|---|---|---|---|
| Loss of <15 letters in visual acuity (%) | 12 | 66% | 98% | 32% (24%, 40%) |
| 24 | 65% | 93% | 28% (19%, 37%) | |
| Gain of ≥15 letters in visual acuity (%) | 12 | 11% | 37% | 26% (17%, 36%) |
| 24 | 9% | 37% | 29% (20%, 39%) | |
| Mean change in visual acuity (letters) (SD) | 12 | −8.5 (17.8) | +11.0 (15.8) | 19.8 (15.9, 23.7) |
| 24 | −9.1 (18.7) | +10.9 (17.3) | 20 (16.0, 24.4) |
| Outcome Measure | Study RVO-1: Sham, n=131; ranibizumab 0.5 mg, n=132 RVO-2: Sham, n=130; ranibizumab 0.5 mg, n=130 | Sham | Ranibizumab 0.5 mg | Estimated Difference (95% CI) Adjusted estimate based on stratified model; p < 0.01 |
|---|---|---|---|---|
| Gain of ≥15 letters in visual acuity (%) | RVO-1 | 29% | 61% | 31% (20%, 43%) |
| Gain of ≥15 letters in visual acuity (%) | RVO-2 | 17% | 48% | 30% (20%, 41%) |
| Outcome Measure | Study D-1: Sham, n=130; ranibizumab 0.3 mg, n=125 D-2: Sham, n=127; ranibizumab 0.3 mg, n=125 | Sham | Ranibizumab 0.3 mg | Estimated Difference (95% CI) Adjusted estimate based on stratified model; p ≤ 0.01 |
|---|---|---|---|---|
| Gain of ≥15 letters in visual acuity (%) | D-1 | 12% | 34% | 21% (11%, 30%) |
| D-2 | 18% | 45% | 24% (14%, 35%) | |
| Loss of <15 letters in visual acuity (%) | D-1 | 92% | 98% | 7% (2%, 13%) |
| D-2 | 90% | 98% | 8% (2%, 14%) | |
| Mean change in visual acuity (letters) | D-1 | 2.3 | 10.9 | 8.5 (5.4, 11.5) |
| D-2 | 2.6 | 12.5 | 9.6 (6.1, 13.0) |
| Outcome Measure | Study D-1: Sham, n=124; ranibizumab 0.3 mg, n=117 D-2: Sham, n=115; ranibizumab 0.3 mg, n=117 | Sham | Ranibizumab 0.3 mg | Estimated Difference (95% CI) Adjusted estimate based on stratified model |
|---|---|---|---|---|
| ≥3-step improvement from baseline in ETDRS-DRSS p < 0.05 for all time points comparing ranibizumab 0.3 mg to sham from Month 12 through Month 24 | D-1 | 2% | 17% | 15% (7%, 22%) |
| D-2 | 0% | 9% | 9% (4%, 14%) | |
| ≥2-step improvement from baseline in ETDRS-DRSS p < 0.05 for all time points comparing ranibizumab 0.3 mg to sham from Month 3 through Month 24 | D-1 | 4% | 39% | 35% (26%, 44%) |
| D-2 | 7% | 37% | 31% (21%, 40%) |
| Ranibizumab group | ||
|---|---|---|
| Outcome Measure (in ETDRS-DRSS) | Eyes with Baseline DME n = 41 | Eyes without Baseline DME n = 148 |
| ≥ 3-step improvement from baseline 95% CI for percentage | 13 (31.7%) (17.5%, 46.0%) | 42 (28.4%) (21.1%, 35.6%) |
| ≥ 2-step improvement from baseline 95% CI for percentage | 24 (58.5%) (43.5%, 73.6%) | 56 (37.8%) (30.0%, 45.7%) |
| Study Arms | Mean change in BCVA from baseline (Letters) | Proportion of patients who gained ≥15 letters from baseline | ||
|---|---|---|---|---|
| Mean (SD) | Estimated Difference (95% CI) Adjusted estimates based on stratified models; p < 0.01 | Percent | Estimated Difference (95% CI) | |
| Group I | 12.1 (10.2) | 10.9 (7.6, 14.3) | 37.1 | 22.6 (9.5, 35.7) |
| Group II | 12.5 (8.8) | 11.4 (8.3, 14.5) | 40.5 | 26.0 (13.1, 38.9) |
| Control (PDT) | 1.4 (12.2) | 14.5 | ||
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
Ready to save on Cimerli?
Compare prescription prices at over 70,000 pharmacies and start saving today—no enrollment required.
Compare Cimerli Prices