FDA Approves Genentech’s Vabysmo for Retinal Vein Occlusion
Genentech announced that the FDA has approved Vabysmo (faricimab-svoa) for the treatment of macular edema following retinal vein occlusion (RVO). This approval is based on positive results from the global phase 3 BALATON and COMINO studies that demonstrated monthly treatment with Vabysmo provided early and sustained improvement in vision in people with branch and central RVO, meeting the primary endpoint of noninferior visual acuity gains at 24 weeks compared to aflibercept. This was further supported by data showing Vabysmo achieved rapid and robust drying of retinal fluid. In BALATON and COMINO, Vabysmo was generally well tolerated, and the safety profile was consistent with previous trials. Vabysmo is the first and only bispecific antibody approved for the eye. RVO is the third indication for Vabysmo, in addition to wet, or neovascular, age-related macular degeneration and diabetic macular edema.
Allgenesis Reports Encouraging Early Data from AG-73305 Phase 2a DME Trial
Allgenesis Biotherapeutics presented encouraging preliminary data from the first-in-human, phase 2a clinical trial of AG-73305 in diabetic macular edema (DME) patients. The data from the 22-patient study demonstrated that AG-73305, a bifunctional Fc-fusion protein designed to block VEGF and integrin pathways, was safe and tolerable after a single intravitreal injection. Efficacy assessments among 4 cohorts showed a mean improvement in best-corrected visual acuity (BCVA) of +6.4 ETDRS letters with central subfield thickness reduction of -100 μm 1 month after the injection. The effects lasted between 12 and 24 weeks, and there was approximately 66% probability that patients did not require rescue by 24 weeks. “The data from our phase 2a study support the hypothesis that blocking multiple pathways in the disease state can provide additional benefits to DME patients in the form of BCVA gains,” Allgenesis CEO Madhu Cherukury, PhD, said in a news release.
Aviceda Glycomimetic Nanoparticle Shows Safety for GA Secondary to AMD
Positive data from Aviceda Therapeutics’ phase 2/3 SIGLEC trial of AVD-104 were presented at EURETINA by Baruch Kuppermann, MD. AVD-104, a novel sialic acid–coated nanoparticle, is being evaluated for patients with geographic atrophy secondary to age-related macular degeneration (AMD). The findings showed continued safety of AVD-104, with no drug-related adverse events or serious adverse events at 3 months in cohorts 1 and 2, at 2 months in cohort 3, and at 1 month in cohort 4. No evidence of any significant dose-limiting toxicity has been observed, locally or systemically. Notably, no drug-related ocular inflammation, retinal vasculitis, choroidal neovascularization, infection, or optic nerve abnormalities were observed in any eyes.
Positive 1-year Data Reported for Gene Therapy in DR
Regenxbio presented positive data from the ongoing phase 2 ALTITUDE trial of ABBV-RGX-314 for the treatment of diabetic retinopathy (DR) without center-involved diabetic macular edema (CI-DME) using in-office suprachoroidal delivery. The data were presented at the 2023 American Academy of Ophthalmology meeting by Mark Barakat, MD. ABBV-RGX-314 is being investigated as a potential one-time gene therapy for the treatment of wet age-related macular degeneration, DR, and other chronic retinal conditions. The data showed that ABBV-RGX-314 continues to be well tolerated in 50 patients from dose levels 1 and 2 (cohorts 1-3) with no drug-related serious adverse events. Dose level 2 prevented disease progression and reduced vision-threatening events in nonproliferative DR at 1 year. Diabetic Retinopathy Severity Scale (DRSS) scores improved in 70.8% of treated patients vs 25% of control patients. No patients had more than 2 steps of DRSS worsening vs 37.5% of control patients. ABBV-RGX-314 reduced vision-threatening events by 89% compared to control.
Inflammasome Therapeutics Gets FDA Approval to Start Dry AMD Clinical Trial
The FDA has granted approval for a phase 1/2 clinical trial of Inflammasome Therapeutics’ Kamuvudines for the treatment of geographic atrophy (GA), according to an announcement by the company. The drug is administered via intravitreal implant for sustained release over 3 months. This is the first clinical trial of an inflammasome inhibitor for treatment of GA. The company has identified and licensed a series of molecules — Kamuvudines — that successfully inhibit inflammasome activation in cell cultures and animal models, and is moving into the clinic for treatment of eye diseases and neurodegenerative diseases. Paul Ashton, chief executive office of Inflammasome Therapeutics, said in a news release, “This is a very important milestone for the company, as it represents the initial clinical trial of several planned trials for our Kamuvudines in a number of other neuroinflammatory conditions.”
OpRegen Shows Rapid Improvement of Outer Retinal Structure
Lineage Cell Therapeutics presented results from its phase 1/2a clinical study of OpRegen (RG6501) currently in development for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD), at the EURETINA Congress, in Amsterdam. The multi-center, dose-escalation trial is evaluating a single administration of OpRegen delivered subretinally, which demonstrated rapid improvement in outer retinal structures. The first 3 cohorts enrolled only legally blind patients with a best-corrected visual acuity (BCVA) of 20/200 or worse. A fourth cohort enrolled 12 patients with BCVA from 20/65 to 20/250, with smaller mean areas of GA. Cohort 4 also included patients treated with a new “thaw-and-inject” formulation of OpRegen, which can be shipped directly to sites and used immediately upon thawing. The presentation was made by Adiel Barak, MD, on behalf of Roche and Genentech.
Switching from Eylea to Vabysmo for DME Doubled Over 12 Months
Spherix Global Insights’ second annual Patient Chart Dynamix: Biologic Switching in Diabetic Macular Edema (US) report revealed that Eylea (Regeneron) has maintained a lead in the market, but the switch to Vabysmo (Genentech) has nearly doubled over the past year. The data are sourced from 128 US ophthalmologists, who reported that more than 40% of their DME patients are currently receiving a second- or subsequent-line biologic treatment. Most biologic switches were reportedly driven by efficacy concerns related to the previous brand. According to a Spherix news release, study results hint that the recent introduction of 8 mg Eylea HD is poised to hinder Vabysmo’s positive momentum, as a considerable portion of the switches to Vabysmo might have gone to Eylea HD if it had been available at the time of evaluation.
LumiThera Receives NEI Grant Extension for LIGHTSITE IIIB Dry AMD Trial
LumiThera announced that it has received a small business innovative research (SBIR) grant from the National Institute of Health (NIH) and the National Eye Institute (NEI) of up to $2.3 million in funding over 2 years. The grant supports LIGHTSITE IIIB, an open-label human clinical trial using photobiomodulation (PBM) to treat intermediate dry age-related macular degeneration (AMD) in subjects who participated in the pivotal LIGHTSITE III trial. The new study will dose patients for 4 rounds of treatment over 14 months. Sham patients in the previous study will be able to cross over and begin PBM treatment. LIGHTSITE III showed a sustained, mean increase in best-corrected visual acuity (BCVA) letter score of >5.0 letters from baseline at the 13-month and 24-month timepoints using the company’s Valeda Light Delivery System.
The study demonstrated disease slowing benefits as fewer PBM-treated eyes progressed to new geographic atrophy.
Survey Highlights Barriers Faced by Women in Ophthalmology
In a survey of more than 100 female ophthalmologists, two-thirds (66%) say their professional ophthalmology experience would be better if they received mentorship from other ophthalmologists of the same gender, yet only 26% received mentorship. The study findings, which were released by Johnson & Johnson Vision, come from Johnson & Johnson MedTech’s Women in Ophthalmology survey. Other key findings include that more than half (56%) of those surveyed say they aspire to mentor new ophthalmologists as they advance in their careers, and over one-third (36%) of those surveyed agree that there is a glass ceiling preventing them from reaching their career aspirations. Lori Tierney, president, Americas, Johnson & Johnson Vision, said, in a news release, “Results from the Women in Ophthalmology Survey highlight the inequities disproportionately faced by women ophthalmologists today, which is unacceptable. At Johnson & Johnson Vision, we are deeply committed to making ophthalmology a more diverse, equitable, and inclusive environment and hope to ignite action to break down the barriers women face to ensure they can thrive in their quest to improve sight for patients.”
Ocutrx Debuts AR Headset for Patients With Advanced Macular Degeneration
Ocutrx debuted its OcuLenz AR/XR augmented reality headset, which uses pixel manipulation software to enhance vision for individuals who have advanced macular degeneration. The headset compensates for central vision loss by shifting pixels from the impaired central vision area to the peripheral vision area. Designed for functionality and mobility, the headset allows users to move freely and perform everyday tasks while wearing it. Additionally, with Wi-Fi and cellular connectivity, the AR/XR headset doubles as a connectivity tool; akin to a computer, tablet, or smartphone. “Our device isn’t merely an advancement in AR technology, it’s a substantial stride toward improving quality of life,” Michael Freeman, Ocutrx cofounder, said in a news release.
First Patients Dosed in Phase 2 Trial of Suprachoroidal OXU-001 for DME
Oxular Limited announced that it has begun dosing patients in its OXEYE phase 2 clinical trial evaluating the company’s suprachoroidal OXU-001, for the treatment of diabetic macular edema (DME). OXU-001 is dexamethasone optimized for delivery to the posterior suprachoroidal space of the eye via Oxulumis, an illuminated microcatheter. This treatment enables routine access closer to the ocular tissues with high disease activity. OXEYE is a two-part, randomized trial designed to evaluate a single administration of OXU-001 over 52 weeks. Part A of the trial is expected to randomize 18 patients who have been previously treated with anti-VEGF therapy, to 1 of 2 dose levels of OXU-001. Part B will be a masked evaluation of 110 DME patients who have either been previously treated with anti-VEGF therapy or are treatment-naïve, randomized to 1 of the 2 dose levels of OXU-001 or Ozurdex (dexamethasone intravitreal implant; Allergan).
Nexus Pharmaceuticals Receives FDA Approval for Fluorescein Injection
Nexus Pharmaceuticals announced it has received FDA approval for its fluorescein injection, USP, a sterile solution indicated in diagnostic fluorescein angiography or angioscopy of the retina and iris vasculature. “Receiving FDA approval for fluorescein injection is another exciting step made toward addressing a supply shortfall of a critical medication on the FDA drug shortage list,” Usman Ahmed, Nexus president and CEO, said in a news release. Nexus Pharmaceuticals’ fluorescein injection, USP 10%, is available in cartons of 10 5 mL single-dose vials.
Pixium Vision Announces 48-month Trial Results in Severe Atrophic AMD
Pixium Vision announced data from a first-in-human trial to assess the efficacy and safety of the PRIMA photovoltaic retinal stimulation microchip, in patients with severe central vision impairment due to dry age-related macular degeneration (AMD). The trial data show that implantation of PRIMA is feasible and well tolerated in all 5 study participants, with no reduction of natural peripheral visual function after 48 months. Using the prosthetic central vision provided by PRIMA, patients reliably recognized letters and sequences of letters with a clinically meaningful improvement in visual acuity of up to 8 lines. The PRIMA retinal prosthesis includes a microchip comprised of 378 pixels that is inserted under the fovea. Each pixel converts light projected from transparent augmented-reality (AR) glasses into an electrical current stimulating the inner retinal cells and restoring central vision in the former scotoma.
Ocular Therapeutix Initiates First Clinical Trial of OTX-TKI in Wet AMD
Ocular Therapeutix announced the initiation of its first pivotal clinical trial to evaluate OTX-TKI, the company’s investigational hydrogel implant being evaluated for the treatment of wet age-related macular degeneration (AMD) and other retinal diseases. The trial will enroll approximately 300 evaluable wet AMD subjects who are treatment naïve in the study eye. The trial will be run primarily at US sites, with subjects randomized to 1 injection of aflibercept (Eylea; Regeneron) or 1 implant of OTX-TKI followed by as needed supplemental anti-VEGF treatment based on prespecified criteria. The safety and efficacy of OTX-TKI will be assessed by measuring best-corrected visual acuity and central subfield thickness at 36 weeks. “This pivotal trial is thoughtfully designed to satisfy the FDA’s latest guidance in wet AMD, while also balancing the needs of subjects who enter it,” David Brown, MD, co-chairman of the medical leadership board at Retina Consultants of America (RCA), said in a news release.
Bausch + Lomb Receives CPT Category 1 Code for XIPERE From AMA
Bausch + Lomb reported that the American Medical Association (AMA) has confirmed assignment of a category 1 Current Procedural Terminology (CPT) code for Xipere, triamcinolone acetonide injectable suspension for the treatment of macular edema associated with uveitis. The AMA granted the CPT code 67516, with support from the American Academy of Ophthalmology and the American Society of Retina Specialists.
“The category 1 code will help facilitate better access and adoption of Xipere and its unique suprachoroidal injection method, which enables targeted delivery of the medication,” Andrew Stewart, president, Global Pharmaceuticals and International Consumer, Bausch + Lomb, said in a news release.
First Patient Dosed in Stargardt Disease Phase 1/2 Clinical Trial
Ocugen announced that the first patient has been dosed in its phase 1/2 GARDian clinical trial for OCU410ST (AAV5-hRORA)—a modifier gene therapy candidate being developed for Stargardt disease. OCU410ST utilizes an AAV delivery platform for the retinal delivery of the RORA (RAR Related Orphan Receptor A) gene. It represents Ocugen’s modifier gene therapy approach, which is based on Nuclear Hormone Receptor (NHR) RORA that regulates pathway links to Stargardt disease, such as lipofuscin formation, oxidative stress, compliment formation, inflammation, and cell survival networks. This phase 1/2 trial will assess the safety of unilateral subretinal administration of OCU410ST in subjects with Stargardt disease and will be conducted in 2 phases.
Byooviz Approved by FDA as Interchangeable with Lucentis
Samsung Bioepis announced that the FDA has approved the supplemental biologics license application (BLA) for Byooviz (ranibizumab-nuna) as a biosimilar product interchangeable with Lucentis (ranibizumab; Genentech). As an interchangeable biosimilar, Byooviz is not expected to result in safety risk or reduction in efficacy, when substituted for Lucentis. The FDA originally approved Byooviz in September 2021 as the first ophthalmology biosimilar in the United States for the treatment of wet age-related macular degeneration, macular edema following retinal vein occlusion, and myopic choroidal neovascularization. This latest approval designates Byooviz as interchangeable across all of these approved indications.
Byooviz has been commercialized by Biogen in the United States since June 2022. In November 2019, Samsung Bioepis and Biogen announced that they had entered into an exclusive commercialization agreement for 2 ophthalmology biosimilar candidates, SB11/Byooviz (ranibizumab) and SB15 (aflibercept) in markets around the world.
Adverum Releases 3-year OPTIC Extension Study Results in Patients with Wet AMD
Adverum Biotechnologies announced updated data from the OPTIC extension study of patients with wet age-related macular degeneration. The outcomes included the following: patients continue to experience long-term benefit from Ixo-vec through 3 years of follow-up, including maintenance of vision, durability of anatomical improvements, and sustained reduction in anti-VEGF treatment burden; patients at the 2E11 dose had an 84% reduction in annualized anti-VEGF injections with 53% of the participants at the 2E11 dose receiving no supplemental injections through 3 years; aflibercept protein levels have been sustained through follow-up for up to 4.5 years post-treatment; best-corrected visual acuity was maintained and central subfield thickness was improved through 3 years; and Ixo-vec was generally well tolerated with dose-dependent inflammation that was responsive to topical steroids. The data were presented during the Retina Subspecialty Day at the 2023 American Academy of Ophthalmology meeting.
Phase 2 ENVISION Study of UBX1325 in Patients with Wet AMD Released
UNITY Biotechnology announced results from Part B of the phase 2 ENVISION study of UBX1325 in patients with wet age-related macular degeneration who were not achieving optimum benefit with their ongoing anti-VEGF therapy.
UBX1325 demonstrated a favorable safety and tolerability profile in the combination and monotherapy arms with no cases of significant intraocular inflammation, retinal artery occlusion, or endophthalmitis. Patients who switched from every-8-week aflibercept (Eylea; Regeneron) to a combination of aflibercept and UBX1325 at week 24 maintained vision gains achieved with aflibercept alone through week 48. Patients in a prespecified subgroup with poor visual acuity (VA) at baseline (≤60 ETDRS letters) gained 3.2 ETDRS letters on combination treatment between weeks 24 and 48. In the UBX1325 monotherapy arm, patients maintained VA for the duration of the study, with a mean change of +0.1 ETDRS letters at 24-weeks and a mean change of -1.5 ETDRS letters at 48 weeks.
Aura Presents Positive Clinical Efficacy Update of Bel-sar for Choroidal Melanoma
Aura Biosciences announced that it received agreement from the FDA for the design and planned analysis of CoMpass, the company’s phase 3 clinical trial of belzupacap sarotalocan (bel-sar; AU-011), for the first-line treatment of adult patients with early-stage choroidal melanoma. Prior to that, Aura reported positive phase 2 safety and efficacy data of bel-sar; with 90% of patients having reached 12 months of follow-up. The results were presented at the 2023 American Academy of Ophthalmology meeting in San Francisco. “We have observed 80% tumor control and 90% visual acuity preservation for patients that have been treated with bel-sar and meet the phase 3 enrollment criteria,” Carol Shields, MD, chief of the ocular oncology service, Wills Eye Hospital, Philadelphia, said in a news release.
XSB-001 Demonstrates Biosimilarity to Reference Ranibizumab for AMD
In a phase 3, multicenter study, XSB-001 demonstrated biosimilarity to reference ranibizumab (Lucentis) for improvement of best-corrected visual acuity (BCVA) in patients with neovascular age-related macular degeneration. In total, 582 patients were randomized to receive intravitreal injections of XSB-001 or reference ranibizumab (0.5 mg) in the study eye once every 4 weeks for 52 weeks. The primary end point was change from baseline in BCVA by ETDRS letters at week 8. Mean BCVA score at baseline was 61.7 and 61.5 ETDRS letters in the XSB-001 and reference ranibizumab groups, respectively. At week 8, the mean change in BCVA from baseline was 4.6 ETDRS letters in the XSB-001 group and 6.4 letters in the reference ranibizumab group. At week 52, mean change in BCVA was 6.4 and 7.8 letters, respectively. Anatomic, safety, pharmacokinetic, and immunogenicity outcomes were also similar between products through 52 weeks of treatment.
Endogena Secures FDA’s Approval of IND for Geographic Atrophy Treatment
Endogena Therapeutics announced that the FDA has granted clearance for the company’s Investigational New Drug (IND) application for EA-2351, a novel compound for the treatment of geographic atrophy. The first-in-human study is set to begin this year. This milestone marks the company’s second program to progress into clinical trials, building on the momentum of its ongoing EA-2353 program for retinitis pigmentosa. While EA-2353 focuses on activating one set of cells in the context of RP, EA-2351 centers on retinal pigment epithelial cells. “We look forward to continuing to develop yet another potential therapy for a condition with a high unmet medical need, thereby providing hope for patients affected by AMD,” Matthias Steger, PhD, MBA, CEO of Endogena, said in a news release.
Kiora’s Photoswitch Demonstrates Meaningful Vision Improvements in RP Patients
Kiora announced top-line results of ABACUS a phase 1/2 clinical trial demonstrating proof-of-concept that KIO-301, the company’s first-in-class small molecule, has the potential to meaningfully improve vision in patients with retinitis pigmentosa who are living with ultra-low vision or complete blindness. The ABACUS study is a first-in-human, open-label, multi-site, single dose-escalating clinical trial for KIO-301, Kiora’s intravitreal molecular photoswitch. The following were among the top-line observations reported at the 2023 American Academy of Ophthalmology meeting: Kinetic visual field (Goldmann perimetry) increased significantly from baseline at days 7 and 14 post-treatment; light perception improved from baseline in patients with no or bare light perception; MRI demonstrated a qualitative increase in brain activity in the primary visual cortex at days 2 and 14 post-injection compared to baseline; patients reported positive impact on overall functional vision as it relates to the use of sight in everyday activities; and KIO-301 is safe and well tolerated with no ocular and nonocular serious adverse events, nor any signs of retinal inflammation. RP