Day 3 of the 17th Congress of the Asia-Pacific Vitreo-retina Society (APVRS 2024) lit up with a flurry of late breaking reports on cutting-edge drugs and devices for retinal treatment.
From promising updates on tyrosine kinase inhibitors (TKIs) and gene therapies to innovative treatments and combination therapies, the session showcased groundbreaking strides poised to transform retinal care—and the audience was here for it.
TKI updates
Tyrosine kinase inhibitors (TKIs) are rewriting the playbook for treating retinal vascular diseases like neovascular age-related macular degeneration (nAMD) and diabetic retinopathy (DR). Unlike the familiar anti-VEGF therapies, which neutralize vascular endothelial growth factor extracellularly, TKIs work from the inside, blocking VEGF signaling intracellularly by inhibiting receptor activity. This novel approach holds the promise of longer-lasting effects and fewer trips to the clinic—a beacon of hope for reducing treatment burdens.
Dr. Nadia Waheed (United States) brought this potential to life with data on the intravitreal axitinib implant (OTX-TKI; Axpaxli™; Ocular Therapeutix, MA, USA). This hydrogel-based, bioresorbable platform offers sustained drug release over eight to nine months, tackling the persistent challenge of frequent injections. The results were impressive.
In a Phase I trial for nAMD, Dr. Waheed revealed that “there was about an 89% [anti-VEGF treatment] reduction for patients [at 52 weeks].” And despite the reduced intervention, outcomes for visual acuity and central subfield thickness (CST) held steady, matching those of bi-monthly aflibercept 2 mg (Eylea®; Bayer & Regeneron).1
But the story doesn’t end there. For severe non-proliferative diabetic retinopathy (NPDR), the HELIOS trial delivered equally compelling results: a 23.1% improvement in DRSS at 48 weeks in the axitinib-treated group, compared to 0% in the sham group. Even better, none of the axitinib-treated patients developed diabetic macular edema (DME) or proliferative diabetic retinopathy (PDR), unlike 33% in the sham group—a promising stride in diabetic eye care.2
Meanwhile, EYP-1901 (Duravyu™; EyePoint Pharmaceuticals, MA, USA), another TKI-based innovation, took the spotlight with its vorolanib-based bioerodible implant. Prof. Gemmy Cheung (Singapore) unveiled 12-month findings from the DAVIO 2 trial.
“Looking all the way to month 12, it is very pleasing to see that the BCVA as well as the CST responses continue to be maintained in the [EYP-1901] group,” she shared. Even more striking, 64% of patients required no supplemental injections at six months, slashing the treatment burden by up to 85%.3
Safety results were equally encouraging. “The safety profile is very favorable, with no related ocular SAEs [serious adverse events] or systematic SAEs,” Prof. Cheung reported, underscoring its potential for safer, less invasive care.
As both OTX-TKI and EYP-1901 advance to pivotal Phase III trials, the promise of TKIs to reshape retinal disease treatment with durability and efficacy remains on the horizon.
Gene therapy updates
Gene therapy is stepping into the spotlight as a revolutionary approach to tackling retinal diseases, offering hope by addressing the root genetic causes of vision loss. Through the delivery of healthy genes or the correction of faulty ones directly within retinal cells, this cutting-edge treatment holds the promise of restoring visual function in ways previously unimaginable.
A/Prof. Gavin Tan (Singapore) began his presentation with a stark reminder of the ongoing struggle in managing nAMD. Chronic undertreatment, driven by injection fatigue and logistical hurdles, often leads to less-than-ideal outcomes for patients. “We know there is a real-world vision decline due to chronic undertreatment in the studies that have followed-up patients in the longer term,” he explained.
Enter ixo-vec (ixoberogene soroparvovec; Adverum Biotechnologies, CA, USA), a one-time injection therapy designed to deliver AAV.7m8, an adeno-associated virus carrying an aflibercept coding sequence controlled by a proprietary expression cassette.
The results from the 52-week LUNA Phase II study were a beacon of hope: 79% of patients required no additional injections while maintaining visual stability. With a strong safety profile and the added appeal of fewer clinic visits, ixo-vec could open a new chapter in nAMD care.4
Adding to the momentum, Prof. Xiaoling Liang (China) shared remarkable findings from the Phase I trial of LX101 (voretigene neparvovec; Innostellar Biotherapeutics, Shanghai, China). This gene therapy targets biallelic RPE65 mutation-associated inherited retinal dystrophy (IRD), a rare genetic condition that severely impairs the visual cycle. Using an AAV2 vector, LX101 delivers a functional RPE65 gene, aiming to restore visual function in affected patients.
The early results were nothing short of inspiring. Prof. Liang revealed that over half of the participants experienced a clinically significant improvement in visual acuity (0.2 LogMAR) after one year. As the pivotal STAR Phase I trial gets underway, LX101’s potential to enhance the lives of IRD patients is becoming increasingly clear.
In other news
ISTH0036 (Isarna Therapeutics, Munich, Germany), is a pioneering antisense therapy targeting TGF-β2 to combat nAMD and DME. This therapy directly addresses fibrosis—a key culprit in retinal degeneration. “Fibrosis leads to RPE degeneration and photoreceptor loss, significantly reducing visual function,” explained Prof. Dr. Marion Munk (Switzerland), underscoring its potential to redefine retinal care.
Phase II data from the BETTER trial offered a glimpse into this promise. Prof. Munk presented findings showing marked reductions in central retinal thickness (CRT) and hyperreflective material, both indicative of reduced fibrosis. Even more striking, 71% of DME patients avoided additional anti-VEGF therapy, a trend similarly reflected in AMD patients.5
Turning to another therapy, Dr. Michael Singer (United States) highlighted real-world data on suprachoroidal triamcinolone acetonide (Xipere®; Bausch & Lomb, Vaughan, Ontario, Canada) for uveitic macular edema (UME). Drawing from the IRIS database, Dr. Singer shared outcomes that paralleled those of the PEACHTREE trial, with 87% of patients remaining rescue-free for six months. The innovative suprachoroidal delivery mechanism not only enhanced durability but also minimized IOP elevation, making it a viable option for high-risk glaucoma patients.
Finally, Dr. Kelvin Teo (Singapore) delved into a comparative study on polypoidal choroidal vasculopathy (PCV), pitting intravitreal aflibercept monotherapy against a combination with reduced-fluence photodynamic therapy (RF-PDT). The results spoke volumes: the combined approach achieved superior polypoidal lesion closure rates at 12 weeks (67% vs. 33%) and reduced the need for injections over 52 weeks. Both groups demonstrated robust visual acuity gains, exceeding two lines, affirming this combination therapy as a powerful tool against PCV.6
Editor’s Note: Reporting for this story took place during the 17th Congress of the Asia-Pacific Vitreo-retina Society (APVRS 2024) from 22-24 November in Singapore.
References
- Eichenbaum DA. 52-week sustained efficacy and treatment burden reduction with OTX-TKI in the US Phase 1 trial for nAMD. Presented at the American Academy of Ophthalmology Annual Meeting, Chicago, October 18-21, 2024. Available at: https://investors.ocutx.com/static-files/a6148d04-e289-40c0-9b2b-233c22ec0458. Accessed on November 24, 2024.
- Dhoot DS. Interim safety and efficacy results from the Phase 1 HELIOS trial of sustained-release axitinib implant (OTX-TKI) for NPDR. Presented at the American Society of Retina Specialists Annual Meeting, Stockholm, July 18, 2024. Available at: https://investors.ocutx.com/static-files/2ba4200f-653f-4d44-8e74-4accf2c956f1. Accessed on November 24, 2024.
- Loewenstein A. The DAVIO 2 Trial: 12-month data from a Phase 2, multicenter, non-inferiority study of a single injection of DURAVYU™ (vorolanib intravitreal insert) vs aflibercept for previously treated wet age-related macular degeneration. Presented at the 24th Euretina Congress, Barcelona, September 19-22, 2024. Available at: https://eyepointpharma.com/wp-content/uploads/2024/09/EURETINA2024_DAVIO2-1yr_Loewenstein_ePoster_FINAL-091824.pdf. Accessed on November 24, 2024.
- Adverum Biotechnologies. Adverum Biotechnologies announces positive 52-week LUNA and 4-year OPTIC results, and provides key pivotal program design elements. News release. November 18, 2024. Available at: https://investors.adverum.com/press_releases/news-details/2024/Adverum-Biotechnologies-Announces-Positive-52-Week-LUNA-and-4-Year-OPTIC-Results-and-Provides-Key-Pivotal-Program-Design-Elements/default.aspx. Accessed on November 24, 2024.
- Munk MR, Gupta V, Bolz M, et al. First results of the phase 2 BETTER trial using intravitreal ISTH0036, a selective TGF-β2 blocking antisense in AMD and DME. IOVS. 2024;65(7):3309.
- Vyas CH, Cheung CMG, Teo KYC, et al. Multicentre, randomised clinical trial comparing intravitreal aflibercept monotherapy versus aflibercept combined with reduced-fluence photodynamic therapy (RF-PDT) for the treatment of polypoidal choroidal vasculopathy. BMJ Open. 2021;11(7):e050252.
