Highlights from the American Academy of Ophthalmology (AAO) Annual Meeting 2022 and press releases until Nov 18, 2022
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The American Academy of Ophthalmology is the world’s largest association of eye physicians and surgeons, with a global community of 32,000 medical doctors. This year’s annual meeting is happening in the Windy City, Chicago.
In this post, you will find a highlight of the latest in macular degeneration from the meeting. As I will update this page when information becomes available, please check back every one to two days.
September 30th, 2022
1. High dose Eylea (aflibercept) for wet AMD
The 48-week results of the Phase 3 PULSAR wet macular degeneration trial for high-dose Eylea were presented at the meeting. Different from the current commercial available Eylea 2mg, the study looked at the high dose, the 8mg formulation.Â
The results showed that out of every four (4) patients, three (3) could be extended to every 12 and every 16-week dosing intervals through week 48.Â
However, the study showed the visual acuity efficacy was numerically lower – but not clinically significant – at once every 12/16 weeks when compared to Eylea 2mg every 8 weeks.  Â
The trial also showed that, even though a higher dose was used, the safety of the 8mg dose was consistent with the established safety profile of Eylea. Â
The company announced that they plan to submit these data to regulatory authorities around the world, but no availability date was specified.
Learn more about aflibercept 8mg …
2. OTX-TKI, a sustained-release hydrogel implant for wet AMDÂ
OTX-TKI is a bioresorbable, extended-delivery hydrogel implant incorporating axitinib, a tyrosine kinase inhibitor, that limits abnormal blood vessel growth.Â
The interim 7-month Phase 1 data was presented at AAO. It showed OTX-TKI was well tolerated and had a good safety profile among different doses. It demonstrated a similar visual acuity efficacy as Eylea at this interim analysis time point, with 80% of the patients receiving of 600-µg OTX-TKI only requiring one implant injection every half of a year. And approximately 50% of patients showed durability of 7.5 months or longer.Â
3. ADVM-022 for wet AMD
ADVM-022 is a gene therapy carrying an aflibercept coding sequence. After a single in-office eye injection (instead of surgery), a patient’s tissue produces aflibercept continuously.Â
The Phase 1 data of the treatment, which was presented at ASRS, was shown again at AAO with additional analyses on the retina fluid. The OPTIC study showed more than 81% reduction in annualized anti-VEGF injection following a single eye injection of ADVM-022 through 2 years. The vision improvement, retina thickness, and retina fluid reduction effectiveness of the treatment were maintained at the end of two years. It was well-tolerated and had a reported manageable safety profile.
The Phase 2 study enrollment has started. and the company anticipates preliminary results throughout 2023.
4. Zimura (avacincaptad pegol) for dry AMD
Zimura is a complement component 5 inhibitor. The inhibition of C5 activities is believed to lead to decreased inflammation and cell death associated with geographic atrophy.Â
The long-awaited second Phase 3 clinical studies of Zimura were presented. The results of the trials showed a significant reduction in the rate of geographic atrophy (GA) at 12 months in patients receiving monthly injections with a favorable safety profile. Â
Additional analyses indicated that patients with an earlier stage of GA had a higher reduction rate. This suggested that this treatment, or even complement system-based treatments, may be more impactful in an earlier stage of GA. Further studies are needed to explore the hypothesis.Â
The manufacturer estimated that New Drug Application (NDA) for GA indication to the U.S. Food and Drug Administration (FDA) might be submitted by quarter one of 2023. And this would make Zimura the second GA treatment to be reviewed by FDA. [Update 11/17/2022: the company has received the FDA Breakthrough Therapy Designation for Zimura and announced that it's on track to complete the NDA submission by the end of 2022.]
Learn more about Zimura and its Phase 3 results…
5. Pegcetacoplan for dry AMD
Pegcetacoplan is a targeted complement component 3 (C3) therapy for geographic atrophy (GA). It is designed to regulate the uncontrolled activation of the complement system, which leads to irreversible lesion growth in GA.Â
The 24-month data from the Phase 3 studies of pegcetacoplan were presented. The treatment showed a higher percentage of patients treated with pegcetacoplan monthly or every other month had a slower GA progression rate.Â
The study results indicated a larger reduction rate in the last six months of the trial. This suggested that this treatment may increase its impact over time. More studies are needed to explore the reason for the accelerated treatment effect.
New analyses presented also showed slowing GA lesion progression with pegcetacoplan preserved the visual function of the retinal cells near the GA lesion border.
The manufacturer of pegcetacoplan announced the U.S. marketing application is under Priority Review. The review is expected to complete on Nov. 26, 2022. [Update 11/18/2022: Due to the submission of the newly available 24-month data to FDA, the updated review completion time is now Feb 26, 2023.]
The company also plans to submit a marketing authorization application to the European Medicines Agency at the end of this year. Â
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Learn more about Pegcetacoplan and its Phase 3 results…
October 1st, 2022
6. JNJ-1887 Gene Therapy for Dry AMD
JNJ-1887 is a gene therapy for geographic atrophy (GA). It is designed to increase the expression of a soluble form of CD59 (sCD59), a complement regulatory protein, intended to protect retinal cells to slow and prevent disease progression.
The Phase 1 data showed the three doses of JNJ-1887 tested showed acceptable safety results over a two-year follow-up period and a continual decline in GA lesion growth over six-month increments. Â
JNJ-1887 has been granted Fast Track designation by the U.S. Food and Drug Administration (FDA) and Advanced Therapy Medicinal Product (ATMP) designation by the European Medicines Agency (EMA).
7. Tinlarebant for Stargardt Disease 1 (a Juvenile Macular Degeneration)Â
Tinlarebant, also known as LBS-008, is a novel oral therapy that prevents the buildup of toxins in the eye that cause Stargardt disease and contribute to advanced dry AMD.Â
The company presented the one-year data from the ongoing two-year Phase 2 clinical study with 13 patients. The study showed that tinalrebant was safe and well tolerated after 12 months of treatment. It also showed that the majority of the patients had a stabilized visual acuity in at least one eye, reduced lesion growth and retina thickness, and no atrophic lesion after one year of treatment.Â
The Phase 3 study has started in multiple countries with an expected study completion date of February 2025. Â
Tinlarebant was granted Fast Track Designation and Rare Pediatric Disease designation in the U.S., and Orphan Drug Designation in the U.S. and Europe for the treatment of STGD1.
Learn more about Tinlarebant…
October 2nd, 2022 (This is the final update)
7. ALK-001 for Stargardt Disease (a Juvenile Macular Degeneration)Â
ALK-001, also known as C20-D3-Vitamin A, is a chemically modified form of vitamin A, currently under development as a once-a-day treatment for Stargardt Disease (STGD1) – as a vitamin A replacement therapy.
Also presented at the ARVO meeting this year, the 24-month Phase 2 study of ALK-001 showed a slower growth rate of retina retinal atrophic lesions compared to the untreated arm. ALK-001 was well tolerated with no reports of night blindness or impaired dark adaption or clinically relevant changes in liver enzymes.
The FDA granted ALK-001 breakthrough therapy designation for Stargardt disease. Phase 3 clinical trial is underway.Â
8. RGX-314 for wet AMD
RGX-314 is a gene therapy carrying a coding sequence similar to ranibizumab (Lucentis). After a single in-office eye injection – a suprachoroidal delivery, a patient’s tissue produces the Lucentis-like anti-VEGF continuously. Â
The Phase 1/2a data presented at the AAO meeting showed, RGX-314 is well-tolerated and demonstrates long-term, durable treatment effects for up to four years.Â
The company also announced positive interim data from its Phase 2 trial. The results showed RGX-314 continued to be well-tolerated with no drug-related serious adverse events. An 85% reduction in treatment burden was observed for one of the doses tested; for another dose group, 67% of the patients were injection-free after the initial treatment.Â
Two Phase 3 trials are active and enrolling. The company estimates FDA BLA submission in 2024.
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What are the different clinical trial phases?
Phase 1: These are small-sized studies of about 20 to 50 people. These people are usually health volunteers. In general, this phase is to evaluate the safety of a new drug, and what happens to the drug in the body.Â
Phase 2: These are medium-sized studies, sometimes including a few hundred patients. This phase is to find out more about the side effects, the optimal dose, and how effective the treatment is in patients.
Phase 3 (also called pivotal trials): These are large-size studies that may include hundreds or thousands of people. A Phase 3 trial compares the new treatment to the current standard of care. If the drug has demonstrated effectiveness with an acceptable safety profile in treating disease (usually, two pivotal trials are required by FDA in the US), the manufacturer can submit a new drug application. Once approved, it can be prescribed to patients.
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(Note: the treatments described here may not be approved by FDA. The information is provided only for educational purposes)Â
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