Advertisement

PentaVision

Retinal Physician

Article

The Diabetic Retinopathy Pipeline

Treatments are in trials from phase 1 to phase 3.

By: Nathalie E. Perez, BS, Lauren C. Kiryakoza, MD, Jayanth Sridhar, MD
Retinal Physician October 1, 2023 Vol 20, Issue October 2023 Page(s): E1-E5

From the Archives

Diabetic retinopathy (DR) and its complications, including diabetic macular edema (DME) and retinal detachment, continue to impose a major disease burden despite recent advances such as intravitreal anti–vascular endothelial growth factor (anti-VEGF) therapy. Ongoing clinical trial efforts are directed toward lengthening the time between intravitreal anti-VEGF injections and discovering alternative routes for therapeutic agents, such as topical agents.1,2 This article will provide an update on clinical trials evaluating oral, intravitreal, surgical, and topical options for DR and DME (Table 1).

Table 1: Summary of Diabetic Retinopathy Clinical Trials
TRIAL AND SPONSOR CONDITION DELIVERY MECHANISM SAMPLE SIZE STUDY DESIGN STATUS
MS-553; Shenzhen Treatment-naïve diabetic retinopathy with CIDME Oral 15 Phase 1 open-label multicenter, dose escalation Recruiting
APX3330; Ocuphire (ZETA-1) Moderately severe to severe NPDR and mild PDR Oral 103 Phase 2 randomized, placebo controlled, double-masked Completed
OCU-200; Ocugen CIDME Intravitreal 28 Phase 1 nonrandomized, open-label, 3+3 design with parallel and sequential dosing Awaiting FDA approval of IND to begin
AR-13503; Aerie Pharmaceuticals Neovascular age-related macular degeneration; DME Intravitreal 18 Phase 1, randomized, open label, sequential assignment Completed
OTX-TKI; Ocular (HELIOS) Moderately severe to severe NPDR Intravitreal 21 Phase 1b, multicenter, double-masked, randomized, parallel Active
UBX1325; Unity (BEHOLD) DME Intravitreal 65 Phase 2a multicenter, randomized, double-masked, sham-controlled Completed
THR-149; Oxurion (KALAHARI) DME Intravitreal 112 Phase 2b randomized, multicenter, parallel assignment Active
KSI-301; Kodiak Sciences (GLOW) Moderately severe to severe NPDR without DME Intravitreal 253 Phase 3, randomized, double masked, sham-controlled, multicenter, 2-arm Active
KSI-301; Kodiak Sciences (GLEAM/GLIMMER) Treatment-naïve DME Intravitreal 460 Phase 3, randomized, double-masked, active comparator-controlled, multicenter, 2-arm Complete
Brolucizumab; Novartis PDR Intravitreal 694 Phase 3, 2-arm, randomized, single-masked, multicenter Active
Aflibercept 8 mg; Regeneron (PHOTON) CIDME Intravitreal 660 Phase 2/3 randomized, double-masked, active-controlled Completed; FDA approved
RGX-314; Regenxbio (ALTITUDE) Diabetic retinopathy without CIDME Surgical 100 Phase 2, randomized, dose-escalation, observation-controlled Active
OCS-01; Oculis (DIAMOND) DME Topical 148 Phase 3, randomized, pivotal, 2-stage, double-masked, multicenter Active
CIDME, center-involving diabetic macular edema; DME, diabetic macular edema; NPDR, nonproliferative diabetic retinopathy; PDR, proliferative diabetic retinopathy

ORAL AGENTS

Phase 1 Trials

MS-553 (Shenzhen MingSight Relin Pharmaceuticals) is a selective protein kinase C-β (PKC-β) inhibitor currently being studied for the treatment of chronic lymphocytic leukemia and small lymphocytic lymphoma.3 In DR, PKC-β activation leads to oxidation-reduction reactions, causing microvascular aberrations, including permeability and angiogenesis.4-6 MS-553 is currently being examined in a phase 1 trial that includes treatment-naïve DR patients with center-involving DME (CIDME).7 There are 3 arms with a low, medium, or high dose of MS-553 taken orally for 8 weeks. As a phase 1 trial, the study’s primary outcome is treatment-emergent adverse events. Secondary outcomes include the mean change in central retina subfield thickness (CRT), mean change in retinal volume, and mean change in best corrected visual acuity (BCVA). The study is ongoing and actively recruiting participants.

Phase 2 Trials

APX3330 (Ocuphire Pharma) is a reduction-oxidation effector factor-1 (Ref-1) inhibitor shown to reduce VEGF and inflammatory cytokines that lead to neovascularization.8,9 The completed phase 2 ZETA-1 trial evaluated the safety and efficacy of APX3330 in 103 participants with moderately severe to severe nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR).10 Participants received either APX3330 600 mg per day or a placebo. The primary endpoint was the percentage of participants with a 2-step or greater improvement in the Diabetic Retinopathy Severity Scale (DRSS) by week 24.10

Results showed the study’s primary endpoint was not met (P=.93).11 However, a statistically significant (P=.04) percentage of subjects (16%) had binocular 3-step or greater worsening in DRSS with placebo administration compared to APX3330 administration (0%).11 APX3330 showed a favorable safety profile, with treatment group subjects experiencing similar adverse events when compared to the control arm. Due to the systemic nature of oral drugs, the binocular DRSS findings may be acceptable as an endpoint for the phase 3 trial planned.11 As such, Ocuphire has an end-of-phase-2 meeting scheduled with the US Food and Drug Administration (FDA) in the second half of 2023, where a decision will be made on whether to proceed to phase 3.11,12

INTRAVITREAL ROUTE

Phase 1 Trials

OCU-200 (Ocugen) is a fusion protein that links both human tumstatin and transferrin. Tumstatin, a domain of type 4 collagen, has been shown to demonstrate antineovascularization properties induced by VEGF.13,14 With the transferrin linked, it is believed to offer improved binding to reduce the number of intravitreal injections required.15 OCU-200 has demonstrated comparable neovascularization reduction to aflibercept in vivo.16

A phase 1 trial will recruit participants with CIDME.17 The 20-week trial consists of 3 cohorts with unilateral dose-escalation up to 2 mg/mL and 1 cohort with OCU-200 in combination with the approved anti-VEGF ranibizumab (Lucentis; Genentech). Its primary endpoint includes study drug–related adverse events, treatment-emergent adverse events, and serious adverse events. Ocugen has submitted an investigational new drug application (IND) and is awaiting FDA clearance to begin enrollment.18

AR-13503 (Aerie Pharmaceuticals) is a sustained-release intravitreal implant that is a Rho kinase inhibitor, a molecule that has been shown to be involved in the pathway of DR through the Rho/Rho-associated coiled-coil containing protein kinase (Rho/ROCK) pathway involving leukocyte adhesion.19,20 This clinical trial was completed in two 24-week stages in patients with neovascular age-related macular degeneration and DME.21 The primary endpoint was the amount of ocular and nonocular treatment-emergent adverse events. Although the study was completed in May 2022, there have not been any released results.21 Aerie Pharmaceuticals was acquired by Alcon in 2022, which may have influenced the delay in top-line data release.22

OTX-TKI (Ocular Therapeutix) is a hydrogel intravitreal implant designed to provide sustained release that incorporates axitinib, a small molecule, selective VEGF inhibitor.23,24 The HELIOS phase 1b trial includes subjects with moderately severe to severe NPDR.25 Participants will receive either an injection of OTX-TKI or a sham injection. Primary outcome measures include treatment emergent adverse events, while secondary outcome measurements include the change in BCVA Early Treatment Diabetic Retinopathy Study (ETDRS) score, change in CRT, rescue therapy requirement, and DRSS changes from baseline. The study has completed enrollment, with 6-month data expected at the beginning of 2024.26

Phase 2 Trials

UBX1325 (Unity Biotechnology) reduces damaged vasculature by inhibiting apoptotic regulatory proteins that are expressed in diseased retinal blood vessels.27 The phase 2a BEHOLD study assessed the safety and efficacy of UBX1325 in patients with DME and CIDME.28 Participants were given either a single intravitreal injection of UBX1325 or a sham control. The primary endpoint was the incidence of treatment emergent adverse events with a secondary outcome measure of the change in BCVA from baseline.

Results of their 48-week data demonstrated a statistically significant and clinically meaningful improvement in BCVA of +6.2 ETDRS letters from baseline in the experimental arm and a +5.6 letter improvement in the sham-treated group.29 53% of patients did not require additional injections throughout the 48 weeks. Patients treated with UBX1325 demonstrated a stable CRT with a mean change of -16.6 μm from baseline at 40 weeks, whereas subjects treated with sham had a mean change of -56.3 μm. Unity plans to begin its phase 2b study comparing UBX1325 to aflibercept in late 2023.29

THR-194 (Oxurion) is a protein that inhibits plasma kallikrein, a component of the plasma kallikrein-kinin system that has been shown to contribute to DME by increasing retinal vascular permeability.30,31 The phase 2 part B KALAHARI trial is studying THR-149 in participants with CIDME.32 Part A aimed to determine the dosage level of THR-149. After post hoc analysis, 3-month data supported the highest dose of THR-149 (0.13 mg) with a mean BCVA gain of +9.3 letters which was maintained up to month 6.30 Part B aims to compare THR-149 to aflibercept with 2 experimental arms and 2 active comparator arms. The experimental arms will consist of 3 monthly THR-149 intravitreal injections, followed by either a sham or aflibercept 2 mg. The active comparator arms will consist of 3 monthly aflibercept intravitreal injections, followed by either a THR-149 or sham injection. Primary outcome measures include the mean change in BCVA ETDRS letters from baseline. Enrollment was recently finalized at 108 participants and top-line data results are expected toward the end of 2023.33

Phase 3 Trials

KSI-301 (Kodiak Sciences), or tarcocimab, is an anti-VEGF therapy designed using the antibody biopolymer conjugate (“ABC”) system to provide a longer lasting intraocular effect.34 The GLOW phase 3 trial aims to assess KSI-301’s potential to provide less frequent intravitreal injections in patients with NPDR without DME.34,35 Participants will receive intravitreal injections every 6 months for 23 months after 3 loading doses or a sham injection with the same treatment schedule. The primary outcome measure is the proportion of eyes that improve 2 or more steps on the ETDRS DRSS. An update is expected in September 2023.34

KSI-301 is also being studied in the GLEAM and GLIMMER trials by Kodiak Sciences. These 2 trials assess the efficacy and safety of KSI-301 compared with intravitreal aflibercept in patients with DME.36,37 The experimental arm received 3 monthly KSI-301 (5 mg) doses and then an individualized dosing interval every 8 to 24 weeks until week 100.36,37 The active comparator arm received 5 monthly aflibercept (2 mg) doses and then one dose every 8 weeks until week 100. The primary outcome measure in both studies is the mean change in BCVA to evaluate KSI-301 5 mg noninferiority to aflibercept 2 mg. July 2023 results from the GLEAM and GLIMMER trials showed the studies failed to meet their primary endpoint. In the GLEAM trial, study participants gained an average of 6.4 eye chart letters compared with 10.3 letters in the aflibercept arm, while in the GLIMMER trial, the tarcocimab arm gained an average of 7.4 eye chart letters compared with 12.2 letters in the aflibercept arm.38 Further, an increased number of cataracts (19%) was observed in the experimental arm compared to the aflibercept arm (9%). Kodiak has decided to discontinue tarcocimab’s development at this time.38

Brolucizumab (Beovu; Novartis) is a single-chain variable antibody fragment that has been approved for age-related macular degeneration and diabetic macular edema.1 Novartis Pharmaceuticals is currently undergoing a phase 3 trial to assess the safety and efficacy of brolucizumab in comparison to panretinal photocoagulation laser (PRP) in patients with PDR. The experimental arm will receive brolucizumab (6 mg) every 12 weeks for 90 weeks after 3 loading injections, while the active comparator arm will receive 1 to 4 PRP sessions until week 12 and as-needed PRP thereafter. The primary endpoint is the change from baseline in BCVA.39 Unfortunately, retinal arterial occlusive vasculitis has been reported with use of intravitreal brolucizumab injections given for DME, and the drug’s use for approved indications has been limited given safety concerns.40 Still, the study remains active and has an expected completion date in August 2024.

High-dose aflibercept (Eylea HD; Regeneron Pharmaceuticals and Bayer) is an 8 mg dose of aflibercept, an anti-VEGF previously approved for DR in a 2mg dose (Eylea). The phase 2/3 PHOTON trial randomized participants with CIDME into either 2 experimental arms or an active comparator arm.41 The experimental arms received aflibercept 8 mg every 12 or 16 weeks after 3 initial monthly doses, while the active comparator arm received aflibercept 2 mg every 8 weeks after 5 initial monthly doses. The primary outcome measure was the change from baseline in BCVA at 48 weeks.

Two-year results showed the mean observed BCVA improvement was 8.4 letters for the Eylea group, 8.8 letters for the 12-week experimental arm, and 7.5 letters for the 16-week experimental arm.42 Importantly, at 2 years, 89% of participants in the 12-week arm and 83% of participants in the 16-week arm did not require dosing interval shortening.42 Additionally, at 2 years, 43% of participants met criteria to maintain a 20-week or more dosing interval.42 In August 2023, the FDA approved the use of 8 mg aflibercept for the treatment of wet age-related macular degeneration, DME, and DR.

SURGICAL OPTIONS

Phase 2 Trials

RGX-314 (Regenxbio) is an adeno-associated virus vector with a transgene for an anti-VEGF antibody fragment that is being studied for gene therapy with a suprachoroidal delivery mechanism.43,44 The phase 2 ALTITUDE trial includes participants with moderately severe to severe NPDR and mild PDR without CIDME. The trial initially included 3 cohorts, with the latter 2 cohorts receiving an increased dose of RGX-314. The primary outcome measure is the proportion of subjects with a 2-step or more improvement in the ETDRS DRSS after 48 weeks.

In 2022, 6-month interim data showed cohorts 1 and 2 had a clinically meaningful improvement with 40% and 11% experiencing a 2-step or more DRSS improvement, respectively, when compared to 10% in the control group.44 Importantly, all cohorts demonstrated good tolerability with no drug-related serious adverse effects. The trial then expanded to include 2 additional cohorts to receive a third, higher dosage level of RGX-314, which is now under way. Interim results in July 2023 demonstrated suprachoroidal delivery of RGX-314 followed by 7 weeks of topical steroid eye drops led to 0 cases of intraocular inflammation.45 Additional interim data are expected in November 2023.45

TOPICAL THERAPIES

Phase 3 Trials

OCS-01 (Oculis) is a high-concentration (15 mg/mL) topical form of dexamethasone.46 In addition to the known effects VEGF has on the pathogenesis of DR, inflammatory cytokines have also been shown to be essential in this process as they are released by ischemic retinal tissue.1,47 The DIAMOND study assessed OCS-01 topical eye drops in participants with DME. Subjects were randomized 2:1 and either received OCS-01 or the vehicle.48 The treatments were administered 6 times daily for 6 weeks, then 3 times daily for another 6 weeks.46

Oculis recently announced the completion of the first stage of the study, which saw a statistically significant improvement in BCVA ETDRS of 7.6 letters when compared to the vehicle with 3.7 letters after 12 weeks.46 Additionally, a statistically significant decrease in CRT was seen in OCS-01 treated participants at 12 weeks when compared to the vehicle group (-61.6 µm vs -16.0 µm, respectively). Stage 2 is expected to begin later this year and will include 2 global trials, each expecting 350 to 450 total participants.46

FUTURE DIRECTIONS

Surely, the future of DR treatment is bright, with multiple phase 1, 2, and 3 clinical trials under way. Topical options and less frequent dosing intervals for intravitreal injections are an exciting introduction to the treatment arsenal. Emerging agents that offer one-time implants or home treatments such as topical or oral options may improve access to care to help reduce disparities seen in medical care. RP

Nathalie E. Perez, BS, is a medical student at Bascom Palmer Eye Institute of the University of Miami Miller School of Medicine in Miami, Florida. She reports no relevant disclosures. Lauren Kiryakoza, MD, is an ophthalmology resident at Bascom Palmer Eye Institute. She reports no relevant disclosures. Jayanth Sridhar, MD, is the chief of ophthalmology and a vitreoretinal surgeon at Olive View Medical Center in Los Angeles, California. He reports consultancy to Allergan, Genentech, Ocuterra, and Regeneron. Reach Dr. Sridhar at jsridhar119@gmail.com. Editor’s note: Hear discussion of this article at www.retinapodcast.com .

REFERENCES

  1. Bahr TA, Bakri SJ. Update on the management of diabetic retinopathy: anti-VEGF agents for the prevention of complications and progression of nonproliferative and proliferative retinopathy. Life (Basel). 2023;13(5):1098. doi:10.3390/life13051098
  2. Kiryakoza L, Sridhar J. DR research roundup: phase 2 and 3. Retina Today. 2022(November/December):e42-44.
  3. A study of the selective PKC-β inhibitor MS-553. Clinicaltrials.gov identifier NCT03492125. Updated March 15, 2023. Accessed September 11, 2023. https://clinicaltrials.gov/show/NCT03492125
  4. Pan D, Xu L, Guo M. The role of protein kinase C in diabetic microvascular complications. Front Endocrinol (Lausanne). 2022;13:973058. doi:10.3389/fendo.2022.973058
  5. Retamal JS, Grace MS, Dill LK, et al. Serotonin-induced vascular permeability is mediated by transient receptor potential vanilloid 4 in the airways and upper gastrointestinal tract of mice. Lab Invest. 2021;101(7):851-864. doi:10.1038/s41374-021-00593-7
  6. Moriya J, Ferrara N. Inhibition of protein kinase C enhances angiogenesis induced by platelet-derived growth factor C in hyperglycemic endothelial cells. Cardiovasc Diabetol. 2015;14:19. doi:10.1186/s12933-015-0180-9
  7. MS-553 in diabetic retinopathy patients with central involved macular edema. Clinicaltrials.gov identifier NCT04187443. Updated March 15, 2023. Accessed September 11, 2023. https://clinicaltrials.gov/show/NCT04187443
  8. Heisel C, Yousif J, Mijiti M, et al. APE1/Ref-1 as a novel target for retinal diseases. J Cell Signal. 2021;2(2):133-138. doi:10.33696/Signaling.2.044
  9. Li Y, Liu X, Zhou T, et al. Inhibition of APE1/Ref-1 redox activity rescues human retinal pigment epithelial cells from oxidative stress and reduces choroidal neovascularization. Redox Biol. 2014;2:485-494. doi:10.1016/j.redox.2014.01.023
  10. Study of the safety and efficacy of APX3330 in diabetic retinopathy. Clinicaltrials.gov identifier: NCT04692688. Updated February 27, 2023. Accessed September 11, 2023. https://clinicaltrials.gov/show/NCT04692688
  11. Boyer DM, Baumal CM, Brigell MP, et al. Safety and efficacy of an oral therapeutic APX3330 from ZETA-1 phase 2 trial in patients with diabetic retinopathy. Presented at: the 46th Annual Macula Society Meeting; February 17, 2023, 2023; Miami, FL.
  12. Ocuphire Pharma announces financial results for first quarter 2023 and provides corporate update. News release. May 15, 2023. Accessed September 11, 2023. https://www.ocuphire.com/news-media/press-releases/detail/403/ocuphire-pharma-announces-financial-results-for-first
  13. Yamamoto Y, Maeshima Y, Kitayama H, et al. Tumstatin peptide, an inhibitor of angiogenesis, prevents glomerular hypertrophy in the early stage of diabetic nephropathy. Diabetes. 2004;53(7):1831-1840. doi:10.2337/diabetes.53.7.1831
  14. Maeshima Y, Colorado PC, Torre A, et al. Distinct antitumor properties of a type IV collagen domain derived from basement membrane. J Biol Chem. 2000;275(28):21340-21348. doi:10.1074/jbc.M001956200
  15. Ocugen, Inc. announced submission of Investigational New Drug application with U.S. FDA to initiate a phase 1 clinical trial evaluating OCU200 for the treatment of diabetic macular edema. News release. February 27, 2023. https://ir.ocugen.com/news-releases/news-release-details/ocugen-inc-announces-submission-investigational-new-drug-1
  16. Upadhyay AK, Arumugham R, Naha P, Singh D. OCU200 (transferrin-tumstatin fusion protein): a potential therapeutic for DME, DR, and wet-AMD. Invest Ophthalmol Vis Sci. 2021;62(8):992-992.
  17. Phase I study to assess the safety and efficacy of OCU200 for center-involved diabetic macular edema (DME). Clinicaltrials.gov identifier: NCT05802329. Updated April 6, 2023. Accessed September 11, 2023. https://clinicaltrials.gov/show/NCT05802329
  18. Ocugen files IND application with US FDA for phase I DME trial. Clinical Trials Arena. February 28, 2023. Accessed September 11, 2023. https://www.clinicaltrialsarena.com/news/ocugen-ind-application-fda-dme/ .
  19. Mateos-Olivares M, García-Onrubia L, Valentín-Bravo FJ, et al. Rho-kinase inhibitors for the treatment of refractory diabetic macular oedema. Cells. 2021;10(7):1683. doi:10.3390/cells10071683
  20. Singer M, Gallagher J. Rho kinase inhibitors for diabetic macular edema. Retinal Physician. 2020;17(September 2020):24-26.
  21. Aerie Pharmaceuticals. A study assessing AR-13503 implant in subjects with nAMD or DME. Clinicaltrials.gov identifier: NCT03835884. Updated February 9, 2023. Accessed September 11, 2023. https://clinicaltrials.gov/show/NCT03835884 .
  22. Alcon completes acquisition of Aerie Pharmaceuticals, Inc., strengthening company’s ophthalmic pharmaceutical business. News release. November 22, 2022. Accessed September 11, 2023. https://investor.alcon.com/news-and-events/press-releases/news-details/2022/Alcon-Completes-Acquisition-of-Aerie-Pharmaceuticals-Inc.-Strengthening-Companys-Ophthalmic-Pharmaceutical-Business/default.aspx
  23. Ocular Therapeutix. OTX-TKI. Accessed September 12, 2023. https://www.ocutx.com/pipeline/retina-treatment/
  24. Hu-Lowe DD, Zou HY, Grazzini ML, et al. Nonclinical antiangiogenesis and antitumor activities of axitinib (AG-013736), an oral, potent, and selective inhibitor of vascular endothelial growth factor receptor tyrosine kinases 1, 2, 3. Clin Cancer Res. 2008;14(22):7272-7283. doi:10.1158/1078-0432.CCR-08-0652
  25. Study to evaluate the safety, tolerability, and efficacy of OTX-TKI in subjects with moderately severe to severe non-proliferative diabetic retinopathy. Clinicaltrials.gov identifier: NCT05695417. Updated June 13, 2023. Accessed September 11, 2023. https://clinicaltrials.gov/show/NCT05695417
  26. Ocular Therapeutix completes enrollment of the HELIOS clinical trial of OTX-TKI for the treatment of diabetic retinopathy. News release. June 7, 2023. Accessed September 11, 2023. https://www.globenewswire.com/en/news-release/2023/06/07/2683695/0/en/Ocular-Therapeutix-Completes-Enrollment-of-the-HELIOS-Clinical-Trial-of-OTX-TKI-for-the-Treatment-of-Diabetic-Retinopathy.html
  27. Unity Biotechnology. Pipeline. Accessed September 11, 2023. https://unitybiotechnology.com/pipeline/
  28. Safety, tolerability and evidence of activity study of UBX1325 in patients with diabetic macular edema (BEHOLD). Clinicaltrials.gov identifier: NCT04857996. Updated April 19, 2023. Accessed September 11, 2023. https://clinicaltrials.gov/show/NCT04857996
  29. Unity biotechnology announces positive 48-week results from phase 2 BEHOLD study of UBX1325 in patients with diabetic macular edema. News release. April 24, 2023. Accessed September 11, 2023. https://ir.unitybiotechnology.com/news-releases/news-release-details/unity-biotechnology-announces-positive-48-week-results-phase-2
  30. Oxurion. Diabetic macular edema. Accessed September 11, 2023. https://oxurion.com/thr-149/
  31. Kita T, Clermont AC, Murugesan N, et al. Plasma kallikrein-kinin system as a VEGF-independent mediator of diabetic macular edema. Diabetes. 2015;64(10):3588-3599. doi:10.2337/db15-0317
  32. A study to evaluate THR-149 treatment for diabetic macular oedema. Clinicaltrials.gov identifier: NCT04527107. Updated January 11, 2023. Accessed September 11, 2023. https://clinicaltrials.gov/show/NCT04527107
  33. Oxurion reaches enrollment target in KALAHARI Phase 2, Part B trial of novel PKal inhibitor THR-149 in diabetic macular edema. News release. May 25, 2023. Accessed September 11, 2023. https://ir.oxurion.com/news-releases/news-release-details/oxurion-reaches-enrollment-target-kalahari-phase-2-part-b-trial
  34. Kodiak Sciences announces first quarter 2023 financial results and recent business highlights. News release. May 15, 2023. Accessed September 11, 2023. https://ir.kodiak.com/news-releases/news-release-details/kodiak-sciences-announces-first-quarter-2023-financial-results
  35. A study to evaluate the efficacy and safety of intravitreal KSI-301 in participants with moderately severe to severe non-proliferative diabetic retinopathy (NPDR). Clinicaltrials.gov identifier: NCT05066230. Updated September 26, 2022. Accessed September 11, 2023. https://clinicaltrials.gov/show/NCT05066230
  36. A study to evaluate the efficacy, durability, and safety of KSI-301 compared to aflibercept in participants with diabetic macular edema (DME). Clinicaltrials.gov identifier: NCT04603937. Updated May 25, 2023. Accessed September 11, 2023. https://clinicaltrials.gov/show/NCT04603937
  37. A trial to evaluate the efficacy, durability, and safety of KSI-301 compared to aflibercept in participants with diabetic macular edema (DME). Clinicaltrials.gov identifier: NCT04611152. Updated May 25, 2023. Accessed September 11, 2023. https://clinicaltrials.gov/show/NCT04611152
  38. Kodiak Sciences announces topline results from its phase 3 studies of tarcocimab tedromer in neovascular age-related macular degeneration and diabetic macular edema and provides update on tarcocimab development program. News release. July 24, 2023. Accessed September 11, 2023. https://www.prnewswire.com/news-releases/kodiak-sciences-announces-topline-results-from-its-phase-3-studies-of-tarcocimab-tedromer-in-neovascular-age-related-macular-degeneration-and-diabetic-macular-edema-and-provides-update-on-tarcocimab-development-program-301883643.html
  39. Study of efficacy and safety of brolucizumab versus panretinal photocoagulation laser in patients with proliferative diabetic retinopathy. Clinicaltrials.gov identifier: NCT04278417. Updated July 11, 2023. Accessed September 11, 2023. https://clinicaltrials.gov/show/NCT04278417
  40. Hirano T, Toriyama Y, Takahashi Y, Hoshiyama K, Murata T. Retinal arterial occlusive vasculitis after multiple intravitreal brolucizumab injections for diabetic macular edema. Am J Ophthalmol Case Rep. 2022;29:101788. doi:10.1016/j.ajoc.2022.101788
  41. Study of a high-dose aflibercept in participants with diabetic eye disease. Clinicaltrials.gov Identifier: NCT04429503. Updated May 24, 2023. Accessed September 11, 2023. https://clinicaltrials.gov/show/NCT04429503
  42. Regeneron. Two-year results for aflibercept 8mg from pivotal PHOTON trial demonstrate durable vision gains at extended dosing intervals in diabetic macular edema. News release. June 27, 2023. Accessed September 11, 2023. https://investor.regeneron.com/news-releases/news-release-details/two-year-results-aflibercept-8-mg-pivotal-photon-trial
  43. RGX-314 gene therapy administered in the suprachoroidal space for participants with diabetic retinopathy (DR) without center involved-diabetic macular edema (CI-DME). Clinicaltrials.gov Identifier: NCT04567550. Updated May 22, 2023. Accessed September 11, 2023. https://clinicaltrials.gov/show/NCT04567550
  44. Regenxbio presents positive interim data from and the expansion of phase II ALTITUTDE trial of RGX-314 for the treatment of diabetic retinopathy using suprachoroidal delivery. News release. November 3, 2022. Accessed September 11, 2023. https://www.prnewswire.com/news-releases/regenxbio-presents-positive-interim-data-from-and-the-expansion-of-phase-ii-altitude-trial-of-rgx-314-for-the-treatment-of-diabetic-retinopathy-using-suprachoroidal-delivery-301667334.html
  45. Regenxbio highlights AAV pipieline with interim results from retinal and Duchenne programs at its virtual investor day on July 11, 2023. News release. July 11, 2023. Accessed Spetember 11, 2023. https://www.prnewswire.com/news-releases/regenxbio-highlights-aav-pipeline-with-interim-results-from-retinal-and-duchenne-programs-at-its-virtual-investor-day-on-july-11-2023-301873891.html
  46. Oculis announces positive top line results from DIAMOND stage 1 phase 3 trial in diabetic macular edema with OCS-01 eye drops. News release. May 22, 2023. Accessed September 11, 2023. https://investors.oculis.com/news-releases/news-release-details/oculis-announces-positive-top-line-results-diamond-stage-1-phase
  47. Joussen AM, Murata T, Tsujikawa A, Kirchhof B, Bursell SE, Adamis AP. Leukocyte-mediated endothelial cell injury and death in the diabetic retina. Am J Pathol. 2001;158(1):147-152. doi:10.1016/S0002-9440(10)63952-1
  48. Multicenter study on the efficacy and safety of OCS-01 in subjects with diabetic macular edema. Clinicaltrials.gov Identifier: NCT05066997. Updated January 17, 2023. Accessed September 11, 2023. https://clinicaltrials.gov/show/NCT05066997

What to Read Next