| Drug Name |
YESAFILI™ (afilbercept-jbcvf) |
OPUVIZ™ (afilbercept-yszy) |
| Active Ingredient |
afilibercept |
afilibercept |
| Date of Approval |
5/20/24 |
5/20/24 |
| Manufacturer |
Biocon Biologics, Inc |
Samsung Bioepis Co., Ltd. |
| Approval Pathways and Indications |
Approval Pathway: BLA
Indication:
YESAFILI™ is a vascular endothelial growth factor (VEGF) inhibitor indicated for the treatment of patients with:
• Neovascular (Wet) Age-Related Macular Degeneration (AMD)
• Macular Edema Following Retinal Vein Occlusion (RVO)
• Diabetic Macular Edema (DME)
• Diabetic Retinopathy (DR) |
Approval Pathway: BLA
Indication:
OPUVIZ™ is a vascular endothelial growth factor (VEGF) inhibitor indicated for the treatment of patients with:
• Neovascular (Wet) Age-Related Macular Degeneration (AMD)
• Macular Edema Following Retinal Vein Occlusion (RVO)
• Diabetic Macular Edema (DME)
• Diabetic Retinopathy (DR) |
| Therapeutic Class |
Ophthalmic Agent; Vascular Endothelial Growth Factor (VEGF) Inhibitor |
Ophthalmic Agent; Vascular Endothelial Growth Factor (VEGF) Inhibitor |
| Formulation |
Injection |
Injection |
| MoA |
Vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PlGF) are members of the VEGF family of angiogenic factors that can act as mitogenic, chemotactic, and vascular permeability factors for endothelial cells. VEGF acts via two receptor tyrosine kinases, VEGFR-1 and VEGFR-2, present on the surface of endothelial cells. PlGF binds only to VEGFR-1, which is also present on the surface of leucocytes. Activation of these receptors by VEGF-A can result in neovascularization and vascular permeability.
Aflibercept products act as a soluble decoy receptor that binds VEGF-A and PlGF, and thereby can inhibit the binding and activation of these cognate VEGF receptors. |
Vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PlGF) are members of the VEGF family of angiogenic factors that can act as mitogenic, chemotactic, and vascular permeability factors for endothelial cells. VEGF acts via two receptor tyrosine kinases, VEGFR-1 and VEGFR-2, present on the surface of endothelial cells. PlGF binds only to VEGFR-1, which is also present on the surface of leucocytes. Activation of these receptors by VEGF-A can result in neovascularization and vascular permeability.
Aflibercept products act as a soluble decoy receptor that binds VEGF-A and PlGF, and thereby can inhibit the binding and activation of these cognate VEGF receptors. |
| Dosing and Administration |
Injection: 2 mg (0.05 mL of 40 mg/mL) solution in a single-dose vial
Neovascular (Wet) Age-Related Macular Degeneration (AMD):
• The recommended dose for YESAFILI™ is 2 mg (0.05 mL of 40 mg/mL solution) administered by intravitreal injection every 4 weeks (approximately every 28 days, monthly) for the first 3 months, followed by 2 mg (0.05 mL of 40 mg/mL solution) via intravitreal injection once every 8 weeks (2 months).
• Although YESAFILI™ may be dosed as frequently as 2 mg every 4 weeks (approximately every 25 days, monthly), additional efficacy was not demonstrated in most patients when aflibercept was dosed every 4 weeks compared to every 8 weeks. Some patients may need every 4 week (monthly) dosing after the first 12 weeks (3 months).
• Although not as effective as the recommended every 8 week dosing regimen, patients may also be treated with one dose every 12 weeks after one year of effective therapy. Patients should be assessed regularly.
Macular Edema Following Retinal Vein Occlusion (RVO):
• The recommended dose for YESAFILI™ is 2 mg (0.05 mL of 40 mg/mL solution) administered by intravitreal injection once every 4 weeks (approximately every 25 days, monthly).
Diabetic Macular Edema (DME) and Diabetic Retinopathy (DR):
• The recommended dose for YESAFILI™ is 2 mg (0.05 mL of 40 mg/mL solution) administered by intravitreal injection every 4 weeks (approximately every 28 days, monthly) for the first 5 injections followed by 2 mg (0.05 mL of 40 mg/mL solution) via intravitreal injection once every 8 weeks (2 months).
• Although YESAFILI™ may be dosed as frequently as 2 mg every 4 weeks (approximately every 25 days, monthly), additional efficacy was not demonstrated in most patients when aflibercept was dosed every 4 weeks compared to every 8 weeks. Some patients may need every 4 week (monthly) dosing after the first 20 weeks (5 months). |
Injection: 2 mg (0.05 mL of 40 mg/mL) solution in a single-dose vial
Neovascular (Wet) Age-Related Macular Degeneration (AMD):
• The recommended dose for OPUVIZ™ is 2 mg (0.05 mL of 40 mg/mL solution) administered by intravitreal injection every 4 weeks (approximately every 28 days, monthly) for the first 3 months, followed by 2 mg (0.05 mL of 40 mg/mL solution) via intravitreal injection once every 8 weeks (2 months).
• Although OPUVIZ™ may be dosed as frequently as 2 mg every 4 weeks (approximately every 25 days, monthly), additional efficacy was not demonstrated in most patients when aflibercept was dosed every 4 weeks compared to every 8 weeks. Some patients may need every 4 week (monthly) dosing after the first 12 weeks (3 months).
• Although not as effective as the recommended every 8 week dosing regimen, patients may also be treated with one dose every 12 weeks after one year of effective therapy. Patients should be assessed regularly.
Macular Edema Following Retinal Vein Occlusion (RVO):
• The recommended dose for OPUVIZ™ is 2 mg (0.05 mL of 40 mg/mL solution) administered by intravitreal injection once every 4 weeks (approximately every 25 days, monthly).
Diabetic Macular Edema (DME) and Diabetic Retinopathy (DR):
• The recommended dose for OPUVIZ™ is 2 mg (0.05 mL of 40 mg/mL solution) administered by intravitreal injection every 4 weeks (approximately every 28 days, monthly) for the first 5 injections followed by 2 mg (0.05 mL of 40 mg/mL solution) via intravitreal injection once every 8 weeks (2 months).
• Although OPUVIZ™ may be dosed as frequently as 2 mg every 4 weeks (approximately every 25 days, monthly), additional efficacy was not demonstrated in most patients when aflibercept was dosed every 4 weeks compared to every 8 weeks. Some patients may need every 4 week (monthly) dosing after the first 20 weeks (5 months). |
| Administered by self or by HCP |
Administered by a HCP |
Administered by HCP |
| Place in Therapy |
The FDA has approved two biosimilars that are interchangeable with EYLEA® (aflibercept). Biocon Biologic’s YESAFILI™ (aflibercept-jbvf) and Samsung Bioepis’ OPUVIZ™ (aflibercept-yszy) are approved to treat neovascular AMD, macular edema following RVO, DME, and DR.
In the United States, approximately 1.5 million adults receive a DME diagnosis, while DR affects 6 million individuals, and AMD impacts 19.8 million Americans. The introduction of YESAFILI™ offers a promising alternative for patients and healthcare providers. Its approval expands the options available for treatment, potentially increasing accessibility and affordability, especially considering the substantial sales of aflibercept in 2023, amounting to approximately $5.89 billion.
Both YESAFILI™ and OPUVIZ™ are administered intravitreally (in the eye) as a 2 mg (0.05 mL of 40 mg/mL) injectable solution. |
The FDA has approved two biosimilars that are interchangeable with EYLEA® (aflibercept). Biocon Biologic’s YESAFILI™ (aflibercept-jbvf) and Samsung Bioepis’ OPUVIZ™ (aflibercept-yszy) are approved to treat neovascular AMD, macular edema following RVO, DME, and DR.
In the United States, approximately 1.5 million adults receive a DME diagnosis, while DR affects 6 million individuals, and AMD impacts 19.8 million Americans. The introduction of OPUVIZ™ offers a promising alternative for patients and healthcare providers. Its approval expands the options available for treatment, potentially increasing accessibility and affordability, especially considering the substantial sales of aflibercept in 2023, amounting to approximately $5.89 billion.
Both YESAFILI™ and OPUVIZ™ are administered intravitreally (in the eye) as a 2 mg (0.05 mL of 40 mg/mL) injectable solution. |
| Expected Market Launch Date |
Yesafili was approved in Europe and the United Kingdom in 2023.
Biocon Biologics, Inc has secured a launch date in Canada of no later than July 1, 2025. The expected market launch date in the United States is unavailable. |
Unavailable |
| New Molecular Entity (NME) or Existing Formulation |
Existing Formulation |
Exisiting Formulation |
| Expected Cost |
Unavailable |
Unavailable |
| Product Discontinuation |
N/A |
N/A |
| Clinical Trials |
A phase 3 study evaluating YESAFILI™ (ClinicalTrials.gov Identifier: NCT03610646) compared the biosimilar to EYLEA® in patients with diabetes mellitus and central DME.
A total of 324 eligible adult subjects were randomly assigned in a 1:1 ratio to receive either intravitreal treatment with YESAFILI™ or EYLEA®. The primary measure of effectiveness was the average change from the baseline in Best Corrected Visual Acuity (BCVA), evaluated using Early Treatment Diabetic Retinopathy Study (ETDRS) letters. Subjects were given intravitreal injections of YESAFILI™ or EYLEA® throughout the 52-week treatment period, with the last dose administered at 48 weeks, and additional doses were given according to the study protocol.
Analysis of the results showed that among the 179 patients who received YESAFILI™, the least squares mean BCVA score was 6.60, with a standard error of 0.548. In comparison, among the 176 patients who received EYLEA®, the least squares mean BCVA score was 6.56, with the same standard error of 0.548. The estimated mean difference between the two treatment groups was reported as 0.04, with a two-sided confidence interval at 90% ranging from -1.16 to 1.24.
In summary, although there was a small difference in the average change in BCVA scores between patients treated with YESAFILI™ and those treated with EYLEA®, this difference was not statistically significant, as indicated by the confidence interval, which includes zero. |
The efficacy of OPUVIZ™ vs. EYLEA®, was established in a phase 3 study that included patients with neovascular AMD (ClinicalTrials.gov Identifier: NCT04450329).
The primary measure of effectiveness was the average change from the baseline in Best Corrected Visual Acuity (BCVA), evaluated using Early Treatment Diabetic Retinopathy Study (ETDRS) letters. 448 subjects were randomized at Week 0 in a 1:1 ratio to either OPUVIZ™ or EYLEA®. Patients randomized to the OPUVIZ™ group received 2 mg (0.05 mL) via intravitreal injection every 4 weeks for the first 3 months, followed by 2 mg (0.05 mL) once every 8 weeks until Week 48.
Analysis of the results showed that among the 224 patients who received OPUVIZ™, the least squares mean BCVA score was 6.7, with a standard error of 0.56. In comparison, among the 224 patients who received EYLEA®, the least squares mean BCVA score was 6.6, with the same standard error of 0.57. Statistical analysis was not stated within the study. |
| Sources |
1. Ltd., B. B. (2024, May 21). Biocon biologics obtains U.S. FDA approval for biosimilar aflibercept for yesafiliTM. enters U.S. ophthalmology market. PR Newswire: press release distribution, targeting, monitoring and marketing.
https://www.prnewswire.com/
news-releases/
biocon-biologics-
obtains-us-fda-approval-for-biosimilar-aflibercept-for
-yesafili-enters-us-
ophthalmology-market-302150830.html
2. Myshko, D. (2024, May 21). Updated: FDA approves first interchangeable biosimilars to eylea. Formulary Watch. https://www.formularywatch.
com/ view/fda-approves-first-interchangeable-biosimilars-to-eylea
|
1. Ltd., B. B. (2024, May 21). Biocon biologics obtains U.S. FDA approval for biosimilar aflibercept for yesafiliTM. enters U.S. ophthalmology market. PR Newswire: press release distribution, targeting, monitoring and marketing.
https://www.prnewswire.com/
news-releases/
biocon-biologics-obtains-
us-fda-approval-for-
biosimilar-aflibercept-
for-yesafili-enters-us-ophthalmology-market-302150830.html
2. Myshko, D. (2024, May 21). Updated: FDA approves first interchangeable biosimilars to eylea. Formulary Watch. https://www.formularywatch.
com/ view/fda-approves-first-interchangeable-biosimilars-to-eylea
|