Vabysmo Drug Information
Generic name: FARICIMAB
Uses of Vabysmo
Neovascular (wet) Age-Related Macular Degeneration (nAMD) 1.2 Diabetic Macular Edema (DME) 1.3
Macular Edema Following Retinal Vein Occlusion (RVO)
Dosage & Administration of Vabysmo
| Read all the instructions carefully before using VABYSMO. | ||
| The VABYSMO carton includes: | ||
| A sterile prefilled syringe in a sealed tray. The prefilled syringe is for treatment of a single eye. | ||
| A sterile injection filter needle (30-gauge × ½ inch, Extra Thin Wall) with an integrated filter in the hub. The injection filter needle is for single use only. | ||
| VABYSMO should be refrigerated at temperatures between 2°C to 8°C (36°F to 46°F). | ||
| Allow VABYSMO to reach room temperature, 20°C to 25°C (68°F to 77°F) before proceeding with the administration. | ||
| Prior to use, keep the sealed tray in the original carton to | ||
| VABYSMO should be inspected visually prior to administration. | ||
| Prefilled Syringe Description | ||
| Figure A | ||
| Use aseptic technique to carry out the following preparation steps: | ||
| Peel the lid off the syringe tray and aseptically remove the prefilled syringe. | ||
| Hold the syringe by the white collar; snap off the syringe cap ( | ||
| Figure B | ||
| Aseptically remove the provided injection filter needle from its packaging. | ||
| Aseptically and firmly attach the injection filter needle onto the syringe Luer lock ( | ||
| Figure C | ||
| Carefully remove the needle cap by pulling it straight off. | ||
| Hold the syringe with the injection filter needle pointing up. Check the syringe for air bubbles. | ||
| If there are any air bubbles, gently tap the syringe with your finger until the bubbles rise to the top ( | ||
| Figure D | ||
| Hold the syringe at eye level and | ||
| Ensure that the injection is given | ||
| Figure E | ||
Side Effects of Vabysmo
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 other clinical trials of the same or another drug and may not reflect the rates observed in practice. The data described below reflect exposure to VABYSMO in 2,567 patients, which constituted the safety population in six Phase 3 studies . Table 1: Common Adverse Reactions (≥ 1%) Adverse Reactions VABYSMO Active Control (aflibercept) AMD N=664 DME N=1,262 RVO N=641 AMD N=662 DME N=625 RVO N=635 Cataract 3% 15% < 1% 2% 12% 1% Conjunctival hemorrhage 7% 8% 3% 8% 7% 4% Vitreous detachment 3% 5% 2% 3% 4% 2% Vitreous floaters 3% 4% 2% 2% 3% 2% Retinal pigment epithelial tear AMD only 3% 1% Intraocular pressure increased 3% 4% 1% 2% 3% 3% Eye pain 3% 3% < 1% 3% 3% < 1% Intraocular inflammation Including iridocyclitis, iritis, uveitis, vitritis 2% 1% 1% 1% 1% < 1% Eye irritation 1% < 1% < 1% < 1% 1% < 1% Lacrimation increased 1% 1% 0 1% < 1% < 1% Ocular discomfort 1% 1% < 1% < 1% < 1% < 1% Less common adverse reactions reported in < 1% of the patients treated with VABYSMO were corneal abrasion, eye pruritus, ocular hyperemia, blurred vision, sensation of foreign body, endophthalmitis, conjunctival hyperaemia, visual acuity reduced, visual acuity reduced transiently, vitreous hemorrhage, retinal tear and rhegmatogenous retinal detachment.
Postmarketing Experience
The following adverse reactions have been identified during postapproval use of VABYSMO. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Eye disorders : retinal vasculitis with or without retinal vascular occlusion.
Warnings & Cautions for Vabysmo
Endophthalmitis and Retinal Detachments Intravitreal injections, including Vabysmo, have been associated with
endophthalmitis and retinal detachments . Proper aseptic injection techniques must always be used when administering VABYSMO. Patients should be instructed to report any signs or symptoms suggestive of endophthalmitis or retinal detachment without delay, to permit prompt and appropriate management.
Increase in Intraocular Pressure Transient increases in intraocular pressure (IOP) have been
seen within 60 minutes of intravitreal injection, including with VABYSMO. IOP and the perfusion of the optic nerve head should be monitored and managed appropriately.
Thromboembolic Events
Although there was a low rate of arterial thromboembolic events (ATEs) observed in the VABYSMO 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). The incidence of reported ATEs in the nAMD studies during the first year was 1% (7 out of 664) in patients treated with VABYSMO compared with 1% (6 out of 662) in patients treated with aflibercept . The incidence of reported ATEs in the DME studies from baseline to week 100 was 5% (64 out of 1,262) in patients treated with VABYSMO compared with 5% (32 out of 625) in patients treated with aflibercept . The incidence of reported ATEs in the RVO studies during the first 6 months was 1.1% (7 out of 641) in patients treated with VABYSMO compared with 1.4% (9 out of 635) in patients treated with aflibercept .
Retinal Vasculitis and/or Retinal Vascular Occlusion Retinal vasculitis and/or retinal vascular occlusion
typically in the presence of intraocular inflammation, have been reported with the use of VABYSMO . Discontinue treatment with VABYSMO in patients who develop these events. Patients should be instructed to report any change in vision without delay.
Pregnancy Safety for Vabysmo
Pregnancy Risk Summary There are no adequate and well-controlled studies of VABYSMO administration in pregnant women. Administration of VABYSMO to pregnant monkeys throughout the period of organogenesis resulted in an increased incidence of abortions at intravenous (IV) doses 158 times the human exposure (based on C max ) of the maximum recommended human dose . Based on the mechanism of action of VEGF and Ang-2 inhibitors, there is a potential risk to female reproductive capacity, and to embryo-fetal development. VABYSMO should not be used during pregnancy unless the potential benefit to the patient outweighs the potential risk to the fetus.
All pregnancies have a background risk of birth defect, loss, and other adverse outcomes. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects is 2%-4% and of miscarriage is 15%-20% of clinically recognized pregnancies.
Data Animal Data An embryo fetal developmental toxicity study was performed on pregnant cynomolgus monkeys. Pregnant animals received 5 weekly IV injections of VABYSMO starting on day 20 of gestation at 1 or 3 mg/kg. A non-dose dependent increase in pregnancy loss (abortions) was observed at both doses evaluated.
Serum exposure (C max ) in pregnant monkeys at the low dose of 1 mg/kg was 158 times the human exposure at the maximum recommended intravitreal dose of 6 mg once every 4 weeks. A no observed adverse effect level (NOAEL) was not identified in this study.
Pediatric Use of Vabysmo
Pediatric Use The safety and efficacy of VABYSMO in pediatric patients have not been established.
Contraindications for Vabysmo
Ocular or Periocular Infections
VABYSMO is contraindicated in patients with ocular or periocular infections.
Active Intraocular Inflammation
VABYSMO is contraindicated in patients with active intraocular inflammation.
Hypersensitivity
VABYSMO is contraindicated in patients with known hypersensitivity to faricimab or any of the excipients in VABYSMO. Hypersensitivity reactions may manifest as rash, pruritus, urticaria, erythema, or severe intraocular inflammation.
Clinical Studies of Vabysmo
Neovascular (wet) Age-Related Macular Degeneration (nAMD)
The safety and efficacy of VABYSMO were assessed in two randomized, multi-center, double-masked, active comparator-controlled, 2-year studies (TENAYA – NCT03823287 and LUCERNE – NCT03823300) in patients with nAMD. A total of 1,329 newly diagnosed, treatment-naïve patients were enrolled in these studies, and 664 patients received at least one dose of VABYSMO. Patient ages ranged from 50 to 99 with a mean of 75.9 years. The studies were identically designed two year studies. Patients were randomized in a 1:1 ratio to one of two treatment arms: 1) aflibercept 2 mg administered fixed every 8 weeks (Q8W) after three initial monthly doses; and VABYSMO 6 mg (0.05 mL of 120 mg/mL solution) administered by intravitreal injection every 4 weeks (approximately every 28 ± 7 days, monthly) for the first 4 doses, followed by optical coherence tomography and visual acuity evaluations 8 and 12 weeks later to determine whether to give a 6 mg (0.05 mL of 120 mg/mL solution) dose via intravitreal injection on one of the following three regimens: 1) Weeks 28 and 44; (also referred to as Q16W dosing); 2) Weeks 24, 36 and 48 (also referred to as Q12W dosing); or 3) Weeks 20, 28, 36 and 44 (also referred to as Q8W dosing). However, the utility of these criteria to guide dosing intervals has not been established.
At week 48, after 4 initial monthly doses in the VABYSMO arm, 45% of patients received the Weeks 28 and 44 dosing, 33% of patients received the Weeks 24, 36 and 48 dosing, and the remaining 22% of patients received dosing every 8 weeks. These percentages are reflective of what happened within the conduct of these trials and indicate that some patients did well on two doses spaced 16 weeks apart, or three doses spaced 12 weeks apart, but the percentages may not be generalizable to a broader nAMD population for a variety of reasons. The inclusion/exclusion criteria limited enrollment to a select subset of treatment-naïve, newly diagnosed nAMD patients and there is no empirical data that a similar magnitude would be observed if eligibility criteria allowed for broader enrollment.
The disease activity criteria, which was instrumental in determining dose frequency, is unvalidated. Stricter criteria would have changed how patients were treated resulting in different percentages of subjects in each dose interval cohort. There was not a similarly dosed aflibercept arm for comparison, which makes the percentages difficult to interpret.
Both studies demonstrated non-inferiority to the comparator control (aflibercept) at the primary endpoint, defined as the mean change from baseline in Best Corrected Visual Acuity (BCVA) when averaged over the week 40, 44, and 48 visits and measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) letter chart. The primary endpoint analysis was a non- inferiority comparison for the mean change in BCVA between the aflibercept and the VABYSMO arm. The lower bound of the 95% confidence interval for the mean change in BCVA could not be lower than minus 4 letters to declare non-inferiority.
In both studies, VABYSMO treated patients had a non-inferior mean change from baseline in BCVA compared to patients treated with aflibercept. Detailed results of both studies are shown in Table 2, Figure 1, and Figure 2 below. The clinical efficacy for the second year of the study has not been reviewed.
Table 2: Primary Endpoint Results Average of weeks 40, 44 and 48 in the TENAYA and LUCERNE Studies TENAYA LUCERNE VABYSMO N = 334 Aflibercept N = 337 VABYSMO N = 331 Aflibercept N = 327 BCVA: Best Corrected Visual Acuity ETDRS: Early Treatment Diabetic Retinopathy Study CI: Confidence Interval LS: Least Square Mean change in BCVA as measured by ETDRS letter score from baseline (95% CI) 5.8 5.1 6.6
Difference in LS mean (95% CI) 0.7 (-1.1, 2.5) 0.0 (-1.7, 1.8)
Figure 1: Mean Change in Visual Acuity from Baseline to Week 48 in TENAYA Figure 2: Mean Change in Visual Acuity from Baseline to Week 48 in LUCERNE Treatment effects in evaluable subgroups (e.g., age, gender, race, baseline visual acuity) in each study were consistent with the results in the overall population. Figure 1 Figure 2
Diabetic Macular Edema (DME)
The safety and efficacy of VABYSMO were assessed in two randomized, multi-center, double-masked, active comparator-controlled 2-year studies (YOSEMITE – NCT03622580 and RHINE – NCT03622593) in patients with DME. A total of 1,891 diabetic patients were enrolled in the two studies with a total of 1,262 patients treated with at least one dose of VABYSMO. Patient ages ranged from 24 to 91 with a mean of 62.2 years. The overall population included both anti-VEGF naïve patients (78%) and patients who had been previously treated with a VEGF inhibitor prior to study participation (22%). The studies were identically designed two year studies. Patients were randomized in a 1:1:1 ratio to one of three treatment regimens: 1) aflibercept Q8W, patients received fixed aflibercept 2 mg administered every 8 weeks (Q8W) after the first five monthly doses; 2) VABYSMO Q8W, patients received fixed VABYSMO 6 mg administered Q8W after the first six monthly doses; and 3) VABYSMO Variable, patients received VABYSMO 6 mg administered every 4 weeks for at least 4 doses and until the central subfield thickness (CST) of the macula measured by optical coherence tomography was less than approximately 325 microns, then the interval of dosing was modified by up to 4 week interval extensions or reductions of up to 8 week interval increments based on CST and visual acuity disease activity criteria at study drug dosing visits.
After 4 initial monthly doses, the patients in the VABYSMO Variable arm received between a minimum of 1 and a maximum of 21 total injections (median of 7 injections) through Week 96 inclusive. At Week 56, 32% of patients had completed at least one Q12W interval followed by one full Q16W interval. Seventeen percent (17%) of patients were treated on Q8W and/or Q4W dosing intervals through Week 56 (7% only on Q4W). These percentages are reflective of what happened within the conduct of these trials, but the percentages may not be generalizable to a broader DME population.
The inclusion/exclusion criteria limited enrollment to a select subset of DME patients and there is no empirical data that a similar magnitude would be observed if eligibility criteria allowed for broader enrollment. The disease activity criteria, which were instrumental in determining dose frequency, are unvalidated. Different criteria would have changed how patients were treated resulting in different percentages of subjects in each dose interval cohort.
There was not a similarly dosed aflibercept arm for comparison which makes the percentages difficult to interpret. Both studies demonstrated non-inferiority to the comparator control (aflibercept) at the primary endpoint, defined as the mean change from baseline in BCVA at year 1 (average of the Week 48, 52, and 56 visits), measured by the ETDRS Letter Score. The primary endpoint analysis was a non-inferiority comparison for the mean change in BCVA between the aflibercept and VABYSMO arms.
The lower bound of the 97.5% confidence interval for the mean change in BCVA could not be lower than minus 4 letters to declare non-inferiority. In both studies, VABYSMO Q8W and VABYSMO Variable treated patients had a non-inferior mean change from baseline in BCVA to the patients treated with aflibercept Q8W at the year 1 primary endpoint. Detailed results of both studies are shown in Table 3, Figure 3, and Figure 4 below.
Table 3: Efficacy Results at Year 1 Average of Weeks 48, 52, 56 and at Year 2 Average of Weeks 92, 96, 100 in the YOSEMITE and RHINE Studies YOSEMITE RHINE Year 1 Year 2 Year 1 Year 2 VABYSMO Q8W N = 315 VABYSMO Variable N = 313 Aflibercept Q8W N = 312 VABYSMO Q8W N = 262 VABYSMO Variable N = 270 Aflibercept Q8W N = 259 VABYSMO Q8W N = 317 VABYSMO Variable N = 319 Aflibercept Q8W N = 315 VABYSMO Q8W N = 259 VABYSMO Variable N = 282 Aflibercept Q8W N = 254 BCVA: Best Corrected Visual Acuity ETDRS: Early Treatment Diabetic Retinopathy Study CI: Confidence Interval LS: Least Square Mean change in BCVA as measured by ETDRS letter score from baseline (97.5% CI year 1 and 95% CI year 2) 10.7 11.6 10.9 10.7 10.7 11.4 11.8 10.8 10.3 10.9 10.1
Difference in LS mean (97.5% CI year 1 and 95% CI year
2) -0.2 (-2.0, 1.6) 0.7 (-1.1, 2.5) -
A non-inferiority margin was not available for year 2 -0.7 1.5 (-0.1
3.2) 0.5 (-1.1, 2.1) 1.5
Figure 3: Mean Change in Visual Acuity from Baseline to Year 2
(Week 100) in YOSEMITE Figure 4: Mean Change in Visual Acuity from Baseline to Year 2 (Week 100) in RHINE Treatment effects in the subgroup of patients who were anti-VEGF naïve prior to study participation were similar to those observed in the overall population. Treatment effects in evaluable subgroups (e.g., by age, gender, race, baseline HbA1c, baseline visual acuity) in each study were generally consistent with the results in the overall population. Figure 3 Figure 4
Macular Edema Following Retinal Vein Occlusion (RVO)
The safety and efficacy of VABYSMO were assessed in two randomized, multicenter, double-masked, studies (BALATON – NCT04740905 in patients with macular edema following branch retinal vein occlusion, and COMINO – NCT04740931 in patients with macular edema following central retinal vein occlusion/hemiretinal vein occlusion). Active comparator-controlled data are available through month 6. A total of 1,282 newly diagnosed, treatment-naïve patients were enrolled in these studies, of which 641 patients received at least one dose of VABYSMO through 6 months. Patient ages ranged from 28 to 93 with a mean of 64 years, and 22 to 100 with a mean of 65 years in BALATON and COMINO, respectively. In both studies, patients were randomized in a 1:1 ratio to either 6 mg VABYSMO administered every 4 weeks, or the control arm receiving aflibercept 2 mg injections every 4 weeks for a total of 6 injections.
In both studies, the VABYSMO 6 mg Q4W arm demonstrated non-inferiority to the comparator control (aflibercept) arm for the primary endpoint, which was defined as the change from baseline in BCVA at week 24, measured by the ETDRS Letter Score. The primary endpoint analysis was a non-inferiority comparison for the mean change in BCVA between the aflibercept and VABYSMO arms, where the lower bound of the 95% confidence interval for the mean change in BCVA could not be lower than minus 4 letters to declare non-inferiority. Detailed results for both BALATON and COMINO studies are shown in Table 4, Figure 5, and Figure 6 below.
Table 4: Primary Endpoint Results at Week 24 in the BALATON and COMINO Studies BALATON COMINO VABYSMO N = 276 Aflibercept N = 277 VABYSMO N = 366 Aflibercept N = 363 BCVA: Best Corrected Visual Acuity ETDRS: Early Treatment Diabetic Retinopathy Study CI: Confidence Interval LS: Least Square Mean change in BCVA as measured by ETDRS letter score from baseline (95% CI) 16.9 17.5 16.9
Difference in LS mean (95% CI) -0.6 (-2.2, 1.1) -0.4 (-2.5, 1.6)
Figure 5: Mean Change in Visual Acuity from Baseline to Week 24 in BALATON Figure 6: Mean Change in Visual Acuity from Baseline to Week 24 in COMINO Figure 5 Figure 6
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.
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