For individuals with wet age-related macular degeneration (AMD), diabetic macular edema (DME) or diabetic retinopathy (DR) whose treatment choices include invasive, burdensome administration that limits treatment uptake, high-dose aflibercept offers less-frequent administration while achieving similar efficacy and safety as the current standard of care (aflibercept 2 mg/EYLEA dosed every 8 weeks or LUCENTIS®
from Genentech dosed every 4 weeks). More convenient for patients and clinicians alike, the 12- and 16-week dosing helps meet a significant unmet need for these patient populations.


  1. Bayer and Regeneron Pharmaceuticals Inc
  2. VEGF inhibitor
  3. Intravitreal (IVT) administration to treat wet AMD, DME and DR
  4. Also being studied to treat macular edema secondary to retinal vein occlusion (RVO) as well as macular telangiectasia type 1
  5. 2.55M people in the G7 markets expected to be drug-treated for wet AMD by 2032
  6. 2.0M people with DME in the G7 markets expected to be drug-treated by 2032
  7. ~130K people with severe non-proliferative DR and proliferative DR in the G7 countries expected to receive drug treatment by 2032

Why is it a drug to watch?

  1. The approval of high-dose aflibercept (8 mg; EYLEA HD) by the U.S. Food and Drug Administration (FDA) was based on positive results from the pivotal phase 3 PULSAR (wet AMD) and PHOTON (DME) studies. Both studies met their primary endpoints with EYLEA HD (administered every 12 or 16 weeks after three initial monthly doses), demonstrating non-inferiority to EYLEA (dosed every 8 weeks following the loading phase) in visual acuity gains from baseline at week 48 while providing a similar safety profile.
  1. The real benefit is expected from the need for fewer injections to reach equivalent visual acuity gains and anatomical features as EYLEA without compromising safety, therefore reducing the treatment burden for patients and healthcare providers. Compelling trial results through two years reinforce the ability of EYLEA HD to prolong treatment intervals of at least 12 weeks to a meaningful proportion of patients:
  • PULSAR for wet AMD (96 weeks):
  • 88% were on the ≥12-week dosing interval
  • 71% were on the ≥16-week dosing interval
  • 47% met the extension criteria for a ≥20-week dosing interval
  • 28% met the extension criteria for a 24-week dosing interval
  • PHOTON for DME (96 weeks):
  • 89% were on the ≥12-week dosing interval
  • 83% were on the ≥16-week dosing interval
  • 43% met the extension criteria for a ≥20-week dosing interval
  • 27% met the extension criteria for a 24-week dosing interval

Review and
approval status

February 2023

  • sNDA/sBLA accepted: EMA

March 2023

  • NDA accepted: Japan PMDA

August 2023

  • sNDA/sBLA accepted: Mainland China NMPA

For patients with wet AMD, DME or DR

  • Approved: U.S. FDA

Actual and expected launch:

  • 2023: United States
  • 2024: Europe, Japan
  • 2025: Mainland China

Patents estimated to expire beginning in 2039

How will high-dose aflibercept impact the market for wet AMD, DME and DR?

  1. The prevalences of wet AMD, DME and diabetic retinopathy are expected to continue increasing with the aging population and greater diabetes burden in the population.
  2. EYLEA HD’s uptake is expected to be challenged by other agents currently approved or in active late-phase development:
  • Vabysmo™ (Roche) for wet AMD and DME
  • Aflibercept biosimilars for wet AMD, DME and DR
  • OCS-01 (Oculis) for DME
  • To a lesser extent:
  • LYTENAVA™ (ONS-5010; Outlook Therapeutics) for wet AMD
  • ABBV-RGX-314 gene therapy (AbbVie and REGENXBIO Inc) for wet AMD and DR
  1. VEGF inhibitors will likely remain the treatment mainstay for wet AMD, DME and DR during this decade and will generate the majority of major-market (U.S., EU5 and Japan) sales.
  1. Clarivate analysts anticipate that EYLEA HD will capture meaningful patient share and become one of the biggest drivers of growth in the wet AMD and DR/DME market.

What gaps in treatment does high-dose aflibercept fill?

The biggest unmet need for patients with DME or wet AMD has been clinically superior therapies with more convenient delivery profiles than available treatments. The frequency and time requirement of clinic visits take a toll on patient and caregiver quality of life and can be particularly burdensome for the working-age population and patients who cannot drive. High-dose aflibercept affords extended dosing intervals while offering favorable safety and efficacy profiles, greatly reducing the administrative and follow-up burden of treatment on patients, caregivers and healthcare providers.

What hurdles might it need to overcome to reach blockbuster status?

The launch of biosimilar versions of aflibercept are expected to erode the patient share of the EYLEA franchise, including EYLEA HD. Clarivate experts expect that, by 2032, approximately 45% of U.S. patients with drug-treated wet AMD receiving aflibercept will receive EYLEA HD while 34% will receive an aflibercept biosimilar. Moreover, they expect that 43% of U.S. patients with wet AMD will receive a competing, newly launched therapy (including biosimilars) by 2032. Novel therapies in development include treatments promising even longer dosing intervals than EYLEA HD and gene therapies that could require a single IVT injection, which would greatly reduce the burden of treatment. Furthermore, EYLEA HD will have to compete with Vabysmo, its biggest rival currently on the market. With a novel mechanism of action, Vabysmo became the first injectable drug allowing administration to up to 16 weeks while providing a safety and efficacy profile consistent with that of EYLEA. Vabysmo experienced rapid uptake shortly after its launch in early 2022, which will have a negative impact on the blockbuster status of EYLEA HD.

expected sales for wet AMD in the G7 markets in 2029
probability of success for diabetic retinopathy in the U.S.
Source: Cortellis Competitive Intelligence, Drug Timeline & Success Rates Prediction current as of November 3, 2023

Drug Timeline &
Success Rates

– Source: Cortellis Competitive Intelligence, Drug Timeline & Success Rates Prediction current as of November 3, 2023

Drugs to Watch 2024

From innovation to bottom line

Access global intelligence, advanced analytics and global experts from Clarivate.

Contact our team