INVESTORS & MEDIA
EYLEA® (aflibercept) Injection Reduced Risk of Developing Vision-Threatening Events by 75% After Two Years in Patients with Diabetic Retinopathy
New data highlight importance of proactive EYLEA treatment as more than half of untreated patients in PANORAMA developed vision-threatening events over two years
High-dose aflibercept development program underway with Phase 3 trials planned for 2020
The two-year pre-specified exploratory data demonstrate that untreated moderately severe and severe NPDR can lead to vision-threatening events, which includes vision-threatening complications (VTCs; proliferative diabetic retinopathy or anterior segment neovascularization) and center-involved diabetic macular edema (CI-DME). Based on a Kaplan-Meier analysis, more than half (58%) of patients in the untreated sham arm developed a VTC or CI-DME within two years of entering the trial, while EYLEA treatment was shown to reduce the likelihood of these vision-threatening events by at least 75% (nominal p<0.0001).
"These data reinforce that regular EYLEA treatment can be highly effective at reducing the risk of new vision-threatening events among patients with moderately severe to severe non-proliferative diabetic retinopathy," said
The two-year results also showed a greater benefit for EYLEA patients treated at regular intervals compared to patients who received EYLEA treatment less frequently. Per the protocol, the group of trial patients who received EYLEA every 8 weeks in the first year were switched to receive it when their doctor determined they needed it (called pro re nata, or PRN) in the second year (i.e., the 8-week/PRN group). The proportion of these patients with a >2-step improvement from baseline in Diabetic Retinopathy Severity Scale (DRSS) scores decreased in the second year (80% improvement at 52 weeks and 50% at 100 weeks).* By comparison, in patients who continued to receive EYLEA every 16 weeks (i.e., the 16-week group), the >2-step DRSS scores remained consistent (65% at 52 weeks vs. 62% at 100 weeks).* In the second year, patients received an average of 1.8 injections in the 8-week/PRN group (out of a possible 6); a review of data from the independent reading center of investigator PRN decisions suggests that some of these patients may have been under-dosed based on the protocol rules of the trial. Patients in the 16-week group received 2.6 injections (out of a possible 3) in the second year.
During the 2-year PANORAMA trial, adverse events were consistent with the known profile of EYLEA. Serious ocular adverse events in the study eye occurred in 2% and 0% of the EYLEA 8-week/PRN and 16-week groups, respectively, and 2% of patients in the sham group. Ocular inflammation occurred in 2% and 1% of patients in the EYLEA treatment groups, respectively, and 1% of patients in the sham group. Anti-platelet trialists' collaboration (APTC)-defined arterial thromboembolic treatment emergent events occurred in 3% and 6% of patients in the EYLEA treatment groups, respectively, and 5% of patients in the sham group.
*p<0.0001 at 52 weeks; nominal p<0.0001 at 100 weeks, as all prespecified endpoints at 100 weeks are considered exploratory.
High-Dose Aflibercept Update
Also presented today was the rationale for high-dose (8 mg) aflibercept clinical trials. A Phase 2 trial (CANDELA) evaluating high-dose aflibercept in wet age-related macular degeneration (wet AMD) is currently enrolling. Phase 3 trials planned to start in 2020 in wet AMD (PULSAR, sponsored by Bayer) and DME (PHOTON, sponsored by Regeneron) will evaluate dosing intervals of 12 weeks and longer.
"Through millions of injections and eight pivotal Phase 3 trials, EYLEA has built a substantial body of evidence and safety profile. High-dose aflibercept will hopefully build on this standard-of-care therapy and represents our ongoing commitment to ophthalmologic research and development," said
The potential use of high-dose aflibercept is currently under clinical development and the safety and efficacy for this use have not been fully evaluated by any regulatory authority.
About the PANORAMA trial
Details on trial design included:
- Three treatment arms – an observational sham injection group and two EYLEA treatment groups. EYLEA was dosed every eight weeks (following five initial monthly doses) or every 16 weeks (following three initial monthly doses and one 8-week interval). At week 52, the 8-week interval group switched to as needed (PRN) dosing determined by the investigator. All patients were followed to week 100.
- Primary endpoint – the primary endpoint was the proportion of patients who experienced a 2-step or greater improvement in the DRSS score from baseline for the combined EYLEA treatment groups at week 24, and for each EYLEA treatment group separately (every 8-week group and every 16-week group) at week 52. The DRSS is a systematic grading scale to assess diabetic retinopathy severity based on photographs of the retina.
- Secondary endpoints – the secondary endpoints included assessment of whether EYLEA reduced the risk of worsening disease – specifically progression to PDR (including anterior segment neovascularization [ASNV]) or the development of CI-DME – as well as change in visual acuity, through week 52.
- Exploratory endpoints – all prespecified endpoints at week 100 (year two) are considered exploratory.
One-year results from PANORAMA were previously reported in
About Diabetic Retinopathy
Approximately eight million people live with diabetic retinopathy, a disease characterized by microvascular damage to the blood vessels in the retina often caused by poor blood sugar control in people with diabetes. The disease generally starts as NPDR and often has no warning signs or symptoms. NPDR may progress to a stage of the disease in which abnormal blood vessels grow onto the surface of the retina and potentially cause severe, vision-threatening complications such as proliferative diabetic retinopathy and anterior segment neovascularization.
DME can occur at any stage of diabetic retinopathy as the blood vessels in the retina become increasingly fragile and leak fluid, potentially causing visual impairment. In the U.S., approximately 1.5 million adults are diagnosed with DME, while approximately 3.5 million people have diabetic retinopathy without DME.
About EYLEA® (aflibercept) Injection
EYLEA® (aflibercept) Injection is a vascular endothelial growth factor (VEGF) inhibitor formulated as an injection for the eye. It is designed to block the growth of new blood vessels and decrease the ability of fluid to pass through blood vessels (vascular permeability) in the eye by blocking VEGF-A and placental growth factor (PLGF), two growth factors involved in angiogenesis. In the U.S., EYLEA is the number one prescribed
IMPORTANT SAFETY INFORMATION FOR EYLEA® (aflibercept) INJECTION
- EYLEA® (aflibercept) Injection is contraindicated in patients with ocular or periocular infections, active intraocular inflammation, or known hypersensitivity to aflibercept or to any of the excipients in EYLEA.
- Intravitreal injections, including those with EYLEA, have been associated with endophthalmitis and retinal detachments. Proper aseptic injection technique must always be used when administering EYLEA. Patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment without delay and should be managed appropriately. Intraocular inflammation has been reported with the use of EYLEA.
- Acute increases in intraocular pressure have been seen within 60 minutes of intravitreal injection, including with EYLEA. 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 EYLEA. 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 EYLEA 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 EYLEA 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 EYLEA 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 EYLEA compared with 4.2% (12 out of 287) in the control group. There were no reported thromboembolic events in the patients treated with EYLEA in the first six months of the RVO studies.
- Serious adverse reactions related to the injection procedure have occurred in <0.1% of intravitreal injections with EYLEA including endophthalmitis and retinal detachment.
- The most common adverse reactions (≥5%) reported in patients receiving EYLEA were conjunctival hemorrhage, eye pain, cataract, vitreous detachment, vitreous floaters, and intraocular pressure increased.
EYLEA® (aflibercept) Injection 2 mg (0.05 mL) is 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), and Diabetic Retinopathy (DR).
DOSAGE AND ADMINISTRATION
Diabetic Macular Edema (DME) and Diabetic Retinopathy (DR)
- The recommended dose for EYLEA is 2 mg (0.05 mL) administered by intravitreal injection every 4 weeks (approximately every 28 days, monthly) for the first 5 injections followed by 2 mg (0.05 mL) via intravitreal injection once every 8 weeks (2 months).
- Although EYLEA 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 EYLEA 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).
Neovascular (Wet) Age-Related Macular Degeneration (AMD)
- The recommended dose for EYLEA is 2 mg (0.05 mL) administered by intravitreal injection every 4 weeks (approximately every 28 days, monthly) for the first 3 months, followed by 2 mg (0.05 mL) via intravitreal injection once every 8 weeks (2 months).
- Although EYLEA 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 EYLEA 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 EYLEA is 2 mg (0.05 mL) administered by intravitreal injection once every 4 weeks (approximately every 25 days, monthly).
For more information, please see full Prescribing Information.
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