INDICATIONS

PAVBLU™ (aflibercept-ayyh) 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).

PAVBLU™ (aflibercept-ayyh) is indicated for the treatment of Neovascular (Wet) Age-Related Macular Degeneration ...Read more

Indications Prescribing Information AmgenSupportPlus.com AmgenBiosimilars.com

PAVBLU™ is a clinically proven biosimilar to EYLEA®

PAVBLU™ is highly similar to EYLEA® based on a totality of evidence, with no clinically meaningful differences in safety and efficacy1-4

BIOSIMILAR DEVELOPMENT STEPS FDA REQUIREMENTS FOR BIOSIMILAR APPROVAL PAVBLU™
Analytical characterization
Nonclinical studies
Clinical pharmacology
Comparative clinical study
Single-transition study

PAVBLU™ is FDA approved for the treatment of patients with:3,*

  • Neovascular (Wet) Age-related Macular Degeneration (AMD)
  • Diabetic Macular Edema (DME)
  • Macular Edema Following Retinal Vein Occlusion (RVO)
  • Diabetic Retinopathy (DR)
  • Neovascular (Wet) Age-related Macular Degeneration (AMD)
  • Macular Edema Following Retinal Vein Occlusion (RVO)
  • Diabetic Macular Edema (DME)
  • Diabetic Retinopathy (DR)

*PAVBLU™ is not indicated for Retinopathy of Prematurity, for which Regeneron has marketing exclusivity.3,5

A randomized, phase 3 study of PAVBLU™ compared to EYLEA® in subjects with neovascular (wet) age-related macular degeneration (AMD)1,6,*

study design in clinical trial of patients treated with PAVBLU™ or Eylea®
  • Dosing: 2 mg (0.05 mL) IVT injection every 4 weeks for the first 3 doses, followed by once every 8 weeks6
  • Primary endpoint:1 Change from baseline in best corrected visual acuity (BCVA) at week 8 (as measured by ETDRS letter score)
    • Difference in mean BCVA change between the two groups was required to fall within a 90% confidence interval of (-3, 3) to establish similarity
  • Secondary efficacy endpoints included:1,6
    • Proportion of patients who maintained vision at week 52 (< 15 in ETDRS letter score lost compared to baseline)
    • BCVA change from baseline through week 52 (ETDRS letter score)
    • Proportion of patients who gained (compared with baseline):
      • ≥ 10 letters of vision at week 8; ≥ 15 letters of vision at week 52 (ETDRS letter score)
    • CNV area (fluorescein angiography) and CST (SD-OCT) mean change from baseline through week 52
  • Secondary safety endpoints included:1,6
    • Proportion of patients with treatment-emergent adverse events (TEAEs)
    • Proportion of patients developing binding antidrug antibodies (ADAs)

*Neovascular (wet) AMD in the study eye with active treatment-naive subfoveal CNV lesions secondary to neovascular (wet) AMD, including juxtafoveal lesions that affect the fovea as confirmed with SD OCT, FA, and/or Fundus Photography (FP) in the study eye.6

CNV = choroidal neovascularization; CST = central subfield thickness; ETDRS = early treatment diabetic retinopathy study; FA = fluorescein angiography; IVT = intravitreal; SD OCT = spectral domain optical coherence tomography.

Patient Characteristics were well balanced between treatment arms1

Selected baseline patient characteristics (mean) PAVBLU™ (n = 288) EYLEA® (n = 288)
Age 76.0 76.0
Duration of disease, weeks: 7.4 6.7
BCVA ETDRS letter score 58.9 57.6
CNV area size (mm2) 8.5 9.3
CST (µm) 438.4 448.8

PAVBLU™ achieved its primary endpoint by demonstrating highly similar efficacy to EYLEA®1

*Estimated using ANCOVA model adjusted for the stratification factors, geographic region (East Asia, Europe, North America), and baseline BCVA as covariates.

No clinically meaningful differences were detected between the treatment groups over the entire study

BCVA (ETDRS letter score) data values provided for select endpoints: PAVBLU™ (n = 273) mean change from baseline (59) at week 8 (+6.5) and week 52 (+7.6); EYLEA® / PAVBLU™ (n = 134) mean change from baseline (57.8) at week 8 (+5.6) and week 52 (+8.0); EYLEA® (n = 136) mean change from baseline (57.2) at week 8 (+7.6) and week 52 (+9.4).1

†Half of patients in the EYLEA® arm were rerandomized to receive PAVBLU™ at week 16 and the first assessment after rerandomization occurred at week 24. Patients who discontinued prior to the first assessment after rerandomization were not included in this secondary endpoint analysis.1

BCVA = best corrected visual acuity; CI = confidence interval.

PAVBLU™ was proven similar to EYLEA® on all secondary endpoints1

Other Secondary Endpoints6

Proportion of subjects who maintained vision at week 52 (lost < 15 letters in ETDRS letter score compared to baseline)

Proportion of subjects who gained ≥ 10 letters of vision at week 8 (ETDRS letter score)

Proportion of subjects who gained ≥ 15 letters of vision at week 52 (ETDRS letter score)

ETDRS = early treatment diabetic retinopathy study.

PAVBLU™ demonstrated no clinically meaningful differences vs EYLEA® in the reduction of retinal thickness1

CST data values provided for select endpoints: PAVBLU™ (n = 273) mean change from baseline (439.4) at week 8 (-145.9) and week 52 (-157.1); EYLEA® / PAVBLU™ (n = 134) mean change from baseline (458.4) at week 8 (-167.4) and week 52 (-177.4); EYLEA® (n = 136) mean change from baseline (440.3) at week 8 (-146.3) and week 52 (-159.1).1

‡Measured by spectral domain optical coherence tomography.1

PAVBLU™ demonstrated no clinically meaningful differences vs EYLEA® in the reduction of CNV area size1

CNV Area Size data values provided for select endpoints: PAVBLU™ (n = 273) mean change from baseline (8.6) at week 8 (-5.0) and week 52 (-6.3); EYLEA® / PAVBLU™ (n = 134) mean change from baseline (9.2) at week 8 (-5.2) and week 52 (-6.4); EYLEA® (n = 136) mean change from baseline (9.5) at week 8 (-5.5) and week 52 (-7.3).1

§Measured by fluorescein angiography.1

You can expect PAVBLU™ to provide highly similar therapeutic benefits as EYLEA® for your patients

PAVBLU™ demonstrated a highly similar safety profile to EYLEA®1

Most common treatment-emergent adverse events (> 1%) THROUGH week 16

Treatment Emergent Adverse Events* PAVBLU™ (n = 288)% (n) EYLEA® (n = 288)% (n)
Conjunctival hemorrhage 4.2% (12) 3.8% (11)
Injection site pain 1.4% (4) 0.3% (1)
Conjunctival hyperemia 1.0% (3) 0.0% (0)
Intraocular injection complication 1.0% (3) 0.0% (0)
Posterior capsule opacification 1.0% (3) 1.0% (3)
Retinal hemorrhage 0.7% (2) 1.4% (4)
Retinal pigment epithelial tear 0.3% (1) 1.4% (4)
Visual acuity reduced 0.3% (1) 1.4% (4)
Dry eye 0.0% (0) 1.4% (4)
Vitreous detachment 0.0% (0) 1.0% (3)
Vitreous floaters 0.0% (0) 1.0% (3)
  • 1 patient (0.3%) on PAVBLU™ developed anti-drug antibodies compared to 4 patients (1.4%) on EYLEA® through week 161
  • Through week 16, the incidence of any Event of Interest (EOI) in the PAVBLU™ and EYLEA® treatment groups was similar (6 [2.1%] and 3 [1.0%], respectively); the incidence, type, and severity of events within each of the individual EOIs was also similar between treatment groups1,†

Comparable safety profile was demonstrated between all treatment groups over the entire study1

Most common treatment-emergent adverse events (> 1%) Post Week-16 rerandomization THROUGH WEEK 52

  • No instances of retinal vasculitis or endophthalmitis were observed in the 52-week study1
  • The incidence of intraocular inflammation was reported in < 1% of patients in all arms of the 52-week study 1

Note: Only treatment-emergent adverse events were summarized. For each adverse event of interest, subjects were included only once, even if they experienced multiple events for that adverse event of interest.1

*Adverse event of interest identified using MedDRA v25.1 terms.1

†Adverse Events of Interest (EOI) prespecified for this study were endophthalmitis, retinal detachment, increase in intraocular pressure, and thromboembolic events.

Transitioning from EYLEA® to PAVBLU™ did not have a clinically meaningful impact on safety for patients1

Important Safety Information

CONTRAINDICATIONS
  • PAVBLU™ is contraindicated in patients with ocular or periocular infections, active intraocular inflammation, or known hypersensitivity to aflibercept or to any of the excipients in PAVBLU™.
WARNINGS AND PRECAUTIONS
  • Intravitreal injections, including those with aflibercept products, have been associated with endophthalmitis and retinal detachments and, more rarely, retinal vasculitis with or without occlusion. Proper aseptic injection technique must always be used when administering PAVBLU™. Patients and/or caregivers should be instructed to report any signs and/or symptoms suggestive of endophthalmitis, retinal detachment, or retinal vasculitis without delay and should be managed appropriately.
  • Acute increases in intraocular pressure have been seen within 60 minutes of intravitreal injection, including with aflibercept products. Sustained increases in intraocular pressure have also been reported after repeated intravitreal dosing with VEGF inhibitors. Intraocular pressure and the perfusion of the optic nerve head should be monitored and managed appropriately.
  • There is a potential risk of arterial thromboembolic events (ATEs) following intravitreal use of VEGF inhibitors, including aflibercept products. ATEs are defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause).
  • The incidence of reported thromboembolic events in wet AMD studies during the first year was 1.8% (32 out of 1824) in the combined group of patients treated with aflibercept compared with 1.5% (9 out of 595) in patients treated with ranibizumab; through 96 weeks, the incidence was 3.3% (60 out of 1824) in the aflibercept group compared with 3.2% (19 out of 595) in the ranibizumab group. The incidence in the DME studies from baseline to week 52 was 3.3% (19 out of 578) in the combined group of patients treated with aflibercept compared with 2.8% (8 out of 287) in the control group; from baseline to week 100, the incidence was 6.4% (37 out of 578) in the combined group of patients treated with aflibercept compared with 4.2% (12 out of 287) in the control group. There were no reported thromboembolic events in the patients treated with aflibercept in the first six months of the RVO studies.
ADVERSE REACTIONS
  • Serious adverse reactions related to the injection procedure have occurred in <0.1% of intravitreal injections with aflibercept including endophthalmitis and retinal detachment.
  • The most common adverse reactions (≥5%) reported in patients receiving aflibercept were conjunctival hemorrhage, eye pain, cataract, vitreous detachment, vitreous floaters, and intraocular pressure increased.
  • Patients may experience temporary visual disturbances after an intravitreal injection with PAVBLU™ and the associated eye examinations. Advise patients not to drive or use machinery until visual function has recovered sufficiently.

You are encouraged to report negative side effects of prescription drugs to the FDA.

Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Please see the full Prescribing Information for additional Important Safety Information.

INDICATIONS

PAVBLU™ (aflibercept-ayyh) is indicated for the treatment of:

  • Neovascular (Wet) Age-Related Macular Degeneration (AMD)
  • Macular Edema following Retinal Vein Occlusion (RVO)
  • Diabetic Macular Edema (DME) 
  • Diabetic Retinopathy (DR)

Important Safety Information

CONTRAINDICATIONS
  • PAVBLU™ is contraindicated in patients with ocular or periocular infections, active intraocular inflammation, or known hypersensitivity to aflibercept or to any of the excipients in PAVBLU™.

EYLEA® is a registered trademark of Regeneron Pharmaceuticals, Inc.

PAVBLU™ is a trademark of Amgen, Inc.

References: 1. Data on file, Amgen. [CSR 20170542]; 2024. 2. US Food and Drug Administration. Guidance for industry: scientific considerations in demonstrating biosimilarity to a reference product. www.fda.gov/media/82647/download. Accessed June 5, 2024. 3. PAVBLU™ (aflibercept-ayyh) Prescribing Information, Amgen. 2024. 4. Seo N, Guan Z, Wang T, et al. Analytical and functional similarity of aflibercept biosimilar ABP 938 with aflibercept reference product. Opthalmol Ther. 2024;13(5):1303-1320. 5. Eylea® [aflibercept] Prescribing Information, Regeneron Pharmaceuticals Inc. 2024. 6. US National Library of Medicine. ClinicalTrials.gov. A study to understand effectiveness and safety of ABP 938 compared to aflibercept (Eylea®) in patients suffering with neovascular age-related macular degeneration [neovascular (wet) AMD]. Updated January 5, 2024. www.clinicaltrials.gov/study/NCT04270747. Accessed June 4, 2024.

References: 1. Data on file, Amgen. [CSR 20170542]; 2024. 2. US Food and Drug Administration. Guidance for industry: scientific considerations in demonstrating biosimilarity to a reference product. www.fda.gov/media/82647/download. Accessed June 5, 2024. 3. PAVBLU™ (aflibercept-ayyh) Prescribing Information, Amgen. 2024. 4. Seo N, Guan Z, Wang T, et al. Analytical and functional similarity of aflibercept biosimilar ABP 938 with aflibercept reference product. Opthalmol Ther. 2024;13(5):1303-1320. 5. Eylea® [aflibercept] Prescribing Information, Regeneron Pharmaceuticals Inc. 2024. 6. US National Library of Medicine. ClinicalTrials.gov. A study to understand effectiveness and safety of ABP 938 compared to aflibercept (Eylea®) in patients suffering with neovascular age-related macular degeneration [neovascular (wet) AMD]. Updated January 5, 2024. www.clinicaltrials.gov/study/NCT04270747. Accessed June 4, 2024.

References: 1. Data on file, Amgen. [CSR 20170542]; 2024. 2. US Food and Drug Administration. Guidance for industry: scientific considerations in demonstrating biosimilarity to a reference product. www.fda.gov/media/82647/download. Accessed June 5, 2024. 3. PAVBLU™ (aflibercept-ayyh) Prescribing Information, Amgen. 2024. 4. Seo N, Guan Z, Wang T, et al. Analytical and functional similarity of aflibercept biosimilar ABP 938 with aflibercept reference product. Opthalmol Ther. 2024;13(5):1303-1320. 5. Eylea® [aflibercept] Prescribing Information, Regeneron Pharmaceuticals Inc. 2024. 6. US National Library of Medicine. ClinicalTrials.gov. A study to understand effectiveness and safety of ABP 938 compared to aflibercept (Eylea®) in patients suffering with neovascular age-related macular degeneration [neovascular (wet) AMD]. Updated January 5, 2024. www.clinicaltrials.gov/study/NCT04270747. Accessed June 4, 2024.