Retina Pipeline: A View Into Ongoing Innovation [Interactive Pipeline]

Knowing where everything stands helps prepare you for the next era in retina.

Content guidance and source: Peter K. Kaiser, MD

Kaiser Headshot

“Keeping an eye on drug development in AMD is difficult. Therapeutic options move from one phase to the next at different times and at different rates, and drugs may start their path in one disease only to find success treating another. We hope you use this poster to understand where we stand in clinical development for AMD treatment as we enter 2020.”

Peter K. Kaiser, MD

This content originally ran as a poster in the November/December issue. Check out the print publication to view the full size poster.

Wet AMD Pipeline

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Dry AMD Pipeline

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Retina specialists have relied on anti-VEGF therapy for more than a decade to treat the wet age-related macular degeneration (AMD) patients we encounter daily. Pegaptanib (Macugen, Bausch + Lomb) was the first anti-VEGF agent on the scene, and it was quickly followed by the more effective ranibizumab (Lucentis, Genentech). Off-label use of bevacizumab (Avastin, Genentech) was soon embraced due to its lower cost and similar efficacy. All three of these agents bind to VEGF isoform VEGF-A. Aflibercept (Eylea, Regeneron), which binds to VEGF-A and B as well as placental growth factor, was the next anti-VEGF agent approved, allowing clinicians to use a drug with expanded VEGF inhibition and longer durability. In October 2019, the US FDA approved the VEGF-A binding agent brolucizumab (Beovu, Novartis) for the treatment of wet AMD.

As we approach 2020, research in wet AMD therapy has made strides in the inhibition of other disease pathways and improvement in existing VEGF pathway blockade. Drugs that interact with angiopoietin, tyrosine kinase, and integrins have entered the scene at various development stages. Combination therapy, too, may be on the horizon, as faricimab (Genentech/Roche) makes its way through phase 3 trials. Finally, sustained delivery strategies and gene therapy are being explored to reduce treatment burden.

Our field has not had the same luck with dry AMD as we have with wet AMD. Numerous trials in dry AMD therapy have failed, but there is cause for hope as several drugs in the pipeline may finally unlock a pharmacotherapy for dry AMD.

Keeping an eye on drug development in AMD is difficult. Therapeutic options move from one phase to the next at different times and at different rates, and drugs may start their path in one disease only to find success treating another.

We’re here to help it keep all straight. Attached in this issue of Retina Today is a poster you can use as a quick reference guide, a snapshot of the pipeline as it stands as of the time of publication. Head into 2020 with this useful chart at the ready.

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Retina Pipeline: Wet AMD

Retina Pipeline: Wet AMD

Extracellular VEGF Pathways

  • pegaptanib (Valeant) FDA-approved
  • ranibizumab (Genentech/Roche) FDA-approved
  • bevacizumab (Genentech/Roche) Off-label
  • bevacizumab (Novartis) FDA-approved
  • abicipar pegol (Allergan)
  • KSI-301 (Kodiak Sciences)
  • FYB201 (biosimilar) (Formycon/Bioeq)
  • PF582 (biosimilar) (Pfenex/Pfizer)
  • razumab (biosimilar) (Intas)
  • CHS3551 (biosimilar) (Coherus Biosciences)
  • SB-11 (biosimilar) (Samsung Bioepis)
  • FYB201 (biosimilar) (Formycon/Bioeq)
  • ONS-510 (biosimilar) (Outlook Therapeutics)
  • Xlucane (biosimilar) (Xbrane)
  • PD807 (biosimilar) (Biopharm)
  • SBS7001 (biosimilar) (Siam Bioscience)
  • ○ ▴ aflibercept (Regeneron/Bayer)
  • ○ ▴ conbercept (Kanghong Biotech)
  • ○ ▴ CHS-2020 (biosimilar) (Coherus Biosciences)
  • ○ ▴ SOK583A1 (biosimilar) (Sandoz/Hexal)
  • ○ ▴ MYL1710 (biosimilar) (Mylan/Momenta)
  • ○ ▴ ALT-L9 (biosimilar) (Alteogen)
  • ○ ▴ OPT-302 (Opthea)

Tyrosine Kinase inhibitor (TKi) Pathways

  • OTX-TKi (Ocular Therapeutix)
  • RTKi-MPP (Kala)
  • GB-102 (Graybug)
  • PAN 90806 (Panoptica)
  • PAN 90806 (Panoptica)
  • sutent (x-82) (Tyrogenex)
  • axitinib (Clearside Biomedical)
  • AR-13503 (Aerie Pharmaceuticals)
  • Caveolin subdomain downstream inhibitor:

  • CVX-51401 (CavtheRx)

TIE2 Activation Pathways

  • faricimab (Genentech/Roche)
  • AXT107 (AsclepiX Therapeutics)

Integrin Pathways

  • volociximab (iveric bio)
  • ❖ ★ SF0166 drop (SciFluor)
  • ❖ ★ AXT107 (AsclepiX Therapeutics)
  • PAN
  • risuteganib (Allegro/Senju)
  • THR-687 (Oxurion)

Gene Therapy

  • RGX-314 (RegenxBio)
  • ▴ ○ ADVM-022 (Adverum)
  • HMR59 (Hemera)

Extended Duration Options

Clearside Suprachoroidal Injection
  • axitinib (Clearside Biomedical)
  • RGX-314 (RegenxBio)
ranibizumab Port Delivery System (PDS)
Polymer Extended Release
  • OTX-TKI (Ocular Therapeutix)
  • GB-102 (Graybug Vision)
  • KSI-301 (Kodiak Sciences)
  • AR-13503 (Aerie Pharmaceuticals)

Retina Pipeline: Dry AMD

Dry AMD Emerging Treatment Strategies

  • Prevent photoreceptor and RPE loss:
    • - Neuroprotection
    • - Reduce toxic by-product accumulation
    • - Visual cycle modulation
    • - Stem Cells
  • Suppress inflammation
  • Other approaches
Dry AMD image

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© sciencesource.com

Dry AMD Emerging Treatment Strategies

  • Prevent photoreceptor and RPE loss:
    • - Neuroprotection
    • - Reduce toxic by-product accumulation
    • - Visual cycle modulation
    • - Stem Cells
  • Suppress inflammation
  • Other approaches
1

Neuroprotection

    Repair mitochondrial dysfunction/oxidative stress:

  • elamipretide (Stealth)
  • risuteganib (Allegro)
  • photobiomodulation (LumiThera)
  • brimonidine tartrate (Allergan)
  • FAILED
  • NT-501 - ciliary neurotrophic factor (Neurotech)
  • tandospirone (Alcon)
  • OT-551 (Othera)
2

Reduce toxic by-product accumulation

    Prevents Amyloid Aβ oligomer assembly:

  • GAL-101 (Galimedix)
  • ALZ-801 (Alzheon)
  • Reduce DHA peroxidation:

  • RT011 (Retrotope)
  • FAILED
  • Glatiramer acetate (Copaxone, FDA-approved, Teva)
  • RN6G (Pfizer)
  • GSK933776 (GSK)
3

Visual cycle modulation

  • ALK-001 (Alkeus)
  • FAILED
  • fenretinide (Sytera)
  • emixustat (Acucela)
  • OT-551 (Othera)
4

Stem Cells

  • Human embryonic stem cells (hESCs)(Lineage Cell Therapeutics)(Regenerative Patch Technologies)
  • Umbilical stem cells (hUTCs)
  • Human retinal progenitor cells (jCyte)
5

Other approaches

    Inflammasome Inhibition:

  • kamuvudine (Inflammasome Therapeutics)
  • Xiflam (OcuNexus)
  • Matrix Modulation:

  • doxycycline (Oracea)
  • HtrA1 inhibitor:

  • FHTR2163 (Genentech/Roche)
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Suppress inflammation

    Complement inhibition location and molecule:

  • ANX007 (Annexon)
  • APL-2 (Apellis)
  • CB2782 (Catalyst)
  • Zimura (Iveric bio)
  • ALXN1720 (Alexion)
  • HMR59 (Hemera)
  • danicopan (Achillion)
  • CR2-fH
  • Ionis-FB-LRX (Ionis)
  • FAILED
  • eculizumab (Alexion)
  • tesidolumab (Novartis)
  • lampalizumab (Genentech/Roche)
  • CLG561 (Novartis)
Peter K. Kaiser, MD Headshot

Peter K. Kaiser, MD

• Medical advisor, Retina Today

• Chaney Family Endowed Chair in Ophthalmology Research; Professor of Ophthalmology, Cleveland Clinic Lerner College of Medicine; staff surgeon in the vitreoretinal department at the Cole Eye Institute, Cleveland Clinic; founding director of the Digital Optical Coherence Tomography Reading Center at the Cole Eye Institute, all in Cleveland, Ohio

• pkkaiser@gmail.com

• Financial disclosure: Advisory board and consultant (Aerie, Aerpio, Alcon, Allegro, Allergan, Annexon Biosciences, AsclepiX, Bayer, Bausch + Lomb, Biogen Idec, Boerenger Ingelheim, Carl Zeiss Meditec, Clearside Biomedical, Eyevensys, Formycon/BioEq GmbH, Galecto Biotech, Galimedix, Glaukos, iRenix, jCyte, Kala Pharmaceuticals, Kanghong, Kodiak, NGM Biopharmaceuticals, Novartis, Ocugenix, Oculis, Omeros, Opthea, Oxurion [Thrombogenics], Regeneron, RegenexBio, Retinal Sciences, Roivant, Santen, SciFluor, Shire, Spark, Stealth Biotherapeutics, Takeda, Verena [Digisight])