| Drug Name |
PAVBLU™ (aflibercept-ayyh) |
| Active Ingredient |
aflibercept |
| Date of Approval |
August 23, 2024 |
| Manufacturer |
Amgen Inc. |
| Approval Pathways and Indications |
Approval Pathway: BLA
Indication: PAVBLU® is indicated for the treatment of neovascular (wet) age-related macular degeneration(AMD), macular edema following retinal vein occlusion(RVO), diabetic macular edema(DME), and diabetic retinopathy(DR). |
| Therapeutic Class |
Vascular endothelial growth factor (VEGF) inhibitor |
| Formulation |
Injection: 2 mg (0.05 mL of 40 mg/mL) solution in a single-dose vial and prefilled syringes |
| 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 soluble decoy receptors that bind VEGF-A and PlGF, and thereby can inhibit the binding and activation of these cognate VEGF receptors. |
| Dosing and Administration |
For AMD, the recommended dose for PAVBLU™ 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).
For RVO, the recommended dose for PAVBLU™ is 2 mg (0.05 mL of 40 mg/mL solution) administered by intravitreal injection once every 4 weeks (approximately every 25 days, monthly).
For DME and DR, the recommended dose for PAVBLU™ 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). |
| Administered by self or by HCP |
Administered by HCP |
| Place in Therapy |
Age-related macular degeneration (AMD) is a leading cause of visual impairment in Europe, with 25.3% of those over 60 affected by early or intermediate stages, and 2.4% with late-stage AMD. By 2050, the number of people with AMD in the EU is expected to increase from 67 million to 77 million, with late AMD cases rising from 400,000 to 700,000 annually.
PAVBLU™ is the fifth approved biosimilar to Eylea. Unlike Eylea, PAVBLU™ is not indicated for retinopathy of prematurity and does not have an interchangeability designation. Previous biosimilars include Formycon’s Ahzantive™ and Sandoz’s Enzeevu™, which are not interchangeable, and Samsung Bioepis/Biogen’s Opuviz™ and Biocon’s Yesafili™, which have received interchangeability designations. Litigation is ongoing to determine if PAVBLU™can be launched at-risk, similar to previous injunctions against other biosimilars.
With Eylea priced at $1,958 per 0.05 mL and Lucentis at $1,242, PAVBLU™could be a more affordable option for treating retinal diseases. |
| Expected Market Launch Date |
Data Unavailable |
| New Molecular Entity (NME) or Existing Formulation |
Existing Formulation |
| Expected Cost |
Data Unavailable |
| Product Discontinuation |
N/A |
| Clinical Trials |
The clinical studies conducted for aflibercept, branded as PAVBLU™, were designed to evaluate its safety and efficacy across various retinal conditions, including AMD, RVO, and DME. In the case of AMD, two large-scale, randomized, multi-center, double-masked, active-controlled studies (VIEW1 and VIEW2) were conducted. These studies involved patients randomly assigned to one of four dosing regimens, with follow-up assessments extending to 96 weeks. For RVO, the clinical trials were similarly rigorous, comprising two randomized, double-masked, sham-controlled studies (COPERNICUS and GALILEO) where patients received either aflibercept or sham injections for a duration of 24 weeks. The DME studies (VIVID and VISTA) followed a similar structure, involving randomized, multi-center, double-masked, controlled studies, where patients were assigned to various dosing regimens of aflibercept or to a control group receiving laser photocoagulation, with efficacy measured up to 100 weeks.
The outcome measures across these studies were focused on visual acuity improvements. In the AMD studies, the primary efficacy endpoint was the proportion of patients who maintained their vision, defined as a loss of fewer than 15 letters in best-corrected visual acuity (BCVA) at 52 weeks. Secondary measures included the mean change in BCVA. In the RVO studies, the primary endpoint was the proportion of patients who gained at least 15 letters in BCVA by week 24. Similarly, in the DME studies, the primary efficacy endpoint was the mean change from baseline in BCVA at weeks 52 and 100, with an additional focus on the proportion of patients who achieved significant visual improvement, defined as a gain of at least 15 letters.
The results from these studies consistently demonstrated the efficacy of aflibercept in maintaining or improving visual acuity across the different conditions. In the AMD studies, approximately 94-95% of patients across different dosing regimens were able to maintain their vision. The RVO studies showed that 56-60% of patients receiving aflibercept achieved significant gains in BCVA, highlighting its effectiveness in this condition as well. In the DME studies, significant improvements in BCVA were sustained over 100 weeks, confirming the long-term efficacy of aflibercept. The safety profile was generally consistent across all studies, with the most common adverse events being conjunctival hemorrhage, eye pain, and cataracts. These findings affirm aflibercept’s role as an effective treatment option for managing serious retinal conditions with a manageable safety profile. |
| Sources |
Lucentis Prices, Coupons and Patient Assistance Programs. Drugs.com. https://www.drugs.com/price-
Eylea Prices, Coupons and Patient Assistance Programs. Drugs.com. https://www.drugs.com/price-guide/eylea
PAVBLU (aflibercept-ayyh) Label. U.S. Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761298s000lbl.pdf. Accessed September 2, 2024. |