After the hubbub of 2023 with the approval of pegcetacoplan (Syfovre, Apellis), avacincaptad pegol (Izervay, Astellas), and 8 mg aflibercept (Eylea HD, Regeneron), we weren’t too disappointed to have a quieter 2024 to regroup. Don’t get us wrong, there have been plenty of innovations to keep us busy, but it’s been more of a watchful year when it comes to the pharmaceutical pipeline.

Just as we were drafting this editorial with that sentiment in mind, two big news stories hit our inboxes. First, LumiThera received FDA authorization to market its Valeda Photobiomodulation (PBM) Light System for the treatment of intermediate AMD based on improvements in vision in treated eyes (+6.2 letters at 21 months [P = .0036] and +5.6 letters at 24 months [P = .0024] compared with sham controls.1 Second, the FDA wanted more time to review data and changed Neurotech Pharmaceutical’s PDUFA goal date to March 2025 for NT-501 (revakinagene taroretcel) for the treatment of macular telangiectasia (Mac-Tel) type 2.2

These updates were a nice reminder of the ups and downs that are so common in clinical research—two steps forward and one step back. Hopefully, by the time we figure out how to integrate PBM into our clinic workflows (treatment cycles comprise nine PBM sessions delivered over 3 to 5 weeks with each cycle performed two to three times annually),3 we will have an FDA decision on the first potential Mac-Tel therapy.

Speaking of ups and downs, an interesting research trend has come to light in this year’s pipeline issue: an unwillingness to give up on promising therapies. Several drug candidates failed to reach their primary endpoints, yet the learnings from those failures have led to a continued push forward. So, don’t dismiss a therapeutic approach just because a readout wasn’t statistically significant. Remember, the phase 3 DERBY trial of pegcetacoplan did not meet its primary endpoint, and yet that drug is now showing a 42% reduction in growth for nonsubfoveal geographic atrophy lesions at 36 months.4 EYP-1901 (EyePoint Pharmaceuticals), ANX007 (Annexon Biosciences), and elamipretide (Stealth Biotherapeutics) have all shown promising benefits without meeting some endpoints and are now in phase 3 clinical trials with updated trial designs, varied dosing schedules, narrowed indications, and/or adjusted primary endpoints.5-7 We are learning better ways to identify clinical benefit and adjusting our trials accordingly.

A particularly good example of this is the tarcocimab tedromer (KSI-301, Kodiak Sciences) program, which has had one of the most fascinating pipeline journeys to date. Although discontinuing the program after GLEAM and GLIMMER failed to meet their primary endpoints for the treatment of diabetic macular edema,8 the company continued to analyze the data and reassess its endpoints and indications.9 The result? Kodiak initiated a new phase 3 trial (DAYBREAK, NCT06556368) investigating tarcocimab in patients with wet AMD—bringing the tally of phase 3 trials for this drug to eight: two are recruiting, two are complete, and four have been terminated (of note, the company released positive data from the GLOW trial currently listed as terminated on clinicaltrials.gov). The company announced plans to submit a biologics license application for three indications—wet AMD, diabetic retinopathy, and retinal vein occlusion—in 2026, pending trial results.10

Retina specialists are a tenacious group, particularly when we recognize the potential to help our patients. This is the type of hard work we love to highlight in our annual pipeline issue—and what drives our field forward. Within this issue, experts share updates on investigational therapies for wet AMD, geographic atrophy, and diabetic eye disease; the latest drug delivery innovations; and a look at the possible applications of nanotechnology in our field. We also have an article discussing the promise of AI in retina and a companion Letter to the Editor reminding everyone that AI faces just as many challenges as our therapeutic pipeline.

Next year is lining up to be another banner year with phase 2 and 3 readouts, potential BLA applications, and (likely) a few disappointments. But remember, failure isn’t always a bad thing. A little tenacity goes a long way.

1. LumiThera obtains FDA authorization of Valeda treatment for dry AMD [press release]. Eyewire+. November 5, 2024. Accessed November 8, 2024. tinyurl.com/y49wukzh

2. Neurotech provides update on BLA for NT-501 as a treatment for macular telangiectasia type 2 [press release]. November 8, 2024. Accessed November 8, 2024. tinyurl.com/mry7kuhc

3. Do D. Photobiomodulation for dry AMD (phase 3 LIGHTSITE III study). Presented at AAO; October 20, 2024; Chicago.

4. Dhoot DS. 36-month efficacy and safety of continuous pegcetacoplan treatment for subfoveal GA: GALE open-label extension study. Presented at AAO; October 18, 2024; Chicago.

5. EyePoint Pharmaceuticals announces topline data from the phase 2 PAVIA trial of Duravyu in non-proliferative diabetic retinopathy [press release]. EyePoint Pharmaceuticals. May 6, 2024. Accessed November 12, 2024. tinyurl.com/4a7y2y32

6. Annexon presents phase 2 vision preservation data with ANX007 in dry AMD patients with less advanced GA at the American Academy of Ophthalmology 2024 Meeting [press release]. Annexon. October 21, 2024. Accessed November 5, 2024. tinyurl.com/5x2kkwb7

7. Heier J. ReCLAIM-2 trial, a phase 2 trial of elamipretide in patients with non-central geographic atrophy. Presented at: American Society of Retina Specialists; July 14, 2022; New York, NY.

8. Kodiak discontinues further development of tarcocimab after phase 3 trial data [press release]. Eyewire+. July 27, 2023. November 8, 2024. tinyurl.com/2a7zux6p

9. Kodiak reboots tarcocimab tedromer development program following strong positive phase 3 DR results [press release]. Eyewire+. November 6, 2023. Accessed November 8, 2024. tinyurl.com/pcpp8y6v

10. Barakat M. Update on antibody biopolymer conjugates: optimizing immediacy and durability. Presented at Innovate Retina 2024; October 17, 2024; Chicago.