Outlook Shares FDA Update on Lytenava for Wet AMD

■ Outlook Therapeutics announced that the FDA has issued a complete response letter regarding its Biologics License Application (BLA) for Lytenava/ONS-5010, an investigational ophthalmic formulation of bevacizumab under development for the treatment of wet age-related macular degeneration (AMD). According to Outlook, the FDA acknowledged that the ONS-5010 NORSE TWO pivotal trial met its safety and efficacy endpoints, but the FDA concluded it could not approve the BLA during this review cycle due to several Chemistry, Manufacturing and Controls issues, as well as open observations from preapproval manufacturing inspections, and a lack of substantial evidence.

“We will request a formal meeting as soon as possible with the FDA to further understand the BLA deficiencies and how best to resolve them. Following this meeting with the FDA, the company will be able to discuss next steps and the expected timing for resolution,” Russell Trenary, president and CEO of Outlook Therapeutics, said in a news release.

Apellis Recommends Discontinuing Use of Syfovre 19-Gauge Filter Needle

■ Apellis Pharmaceuticals provided an update on the events of retinal vasculitis reported in real-world treatment with Syfovre (pegcetacoplan injection) for geographic atrophy (GA) secondary to AMD. As part of the comprehensive investigation into the real-world safety events, internal structural variations were identified in the specific 19-gauge x 1.5 inch filter needle included in certain injection kits. The company recommends that practitioners immediately discontinue use of any injection kits that contain the 19-gauge filter needle and use injection kits with the 18-gauge filter needle, which are already in distribution. While injection kits previously contained 1 of 2 types of filter needles (either 18- or 19-gauge), Apellis is now exclusively distributing injection kits with the 18-gauge filter needle. “This recommendation is out of an abundance of caution as patient safety is our top priority,” Caroline Baumal, MD, chief medical officer of Apellis, said in a news release.

Positive Results Seen for Aflibercept 8 mg at Extended Dosing Intervals

■ Regeneron announced positive 2-year results from the PULSAR trial investigating aflibercept 8 mg in patients with wet AMD. Patients were initially randomized to either 12-week or 16-week dosing intervals, after 3 initial monthly doses, and were able to shorten or extend dosing intervals if prespecified criteria were met. Findings include: 88% of patients were on ≥12-week dosing at the end of 2 years; 78% maintained ≥12-week dosing throughout 2 years; 71% met the extension criteria for even longer dosing intervals, including 47% for ≥20-week intervals and 28% for 24-week intervals; and visual gains and safety of aflibercept 8 mg remained consistent with the established profile of Eylea (aflibercept) 2 mg injection.

“These data are consistent with the results from the PHOTON trial in diabetic macular edema, with both trials demonstrating a consistent safety profile with substantially fewer treatments than Eylea,” Charles C. Wykoff, MD, PhD, director of research at Retina Consultants of Texas and a trial investigator, said in a news release.

BioLight and Alexion Partner on Natural Tears Retina Disease Diagnosis Tool

■ BioLight reported that it has signed a research collaboration agreement with Alexion (AstraZeneca Rare Disease), focusing on exploring technology that utilizes natural tears for the potential diagnosis of retinal diseases. The team is funding a study that will evaluate a screening technique that analyzes components of the tear film. The research will be conducted at the Tel Aviv Medical Center.

HuidaGene Gets Rare Pediatric Disease Designation for Retinal Diseases Drug

■ The FDA has granted both rare pediatric disease designation and orphan drug designation to HuidaGene Therapeutics’s HG004, for the treatment of inherited retinal disease caused by RPE65 mutations. In a news release, Linyu Shi, PhD, HuidaGene cofounder and chief scientific officer said, “Data from our preclinical studies have shown that HG004 demonstrates significant superiority in the recovery of retinal function of RPE65^-/- mice. We are committed to delivering transformative genetic medicines for rare genetic diseases globally.”

Mylight Phase 2 Biosimilar Study Meets Primary Efficacy Endpoint

■ Sandoz released positive results from its Mylight phase 3 study for its biosimilar aflibercept, for patients with wet macular degeneration. The study met its primary efficacy endpoint, showing therapeutic equivalence in mean change of best-corrected visual acuity from baseline to week 8 between the biosimilar aflibercept and the reference biologic, Eylea (Regeneron). Safety, immunogenicity, and pharmacokinetics results further confirm that there is no clinically meaningful difference between the products.

EyePoint Presents Interim DAVIO 2 Data at OIS Retina Summit

■ EyePoint Pharmaceuticals presented interim masked safety data from its phase 2 DAVIO 2 clinical trial of EYP-1901, a potential sustained delivery maintenance treatment for wet AMD, at the OIS Retina Innovation Summit in Seattle. In a news release, Jay S. Duker, MD, EyePoint president and CEO, summarized the outcomes, stating that “EYP-1901 continues to demonstrate an excellent safety profile in the phase 2 DAVIO 2 trial with no reported drug-related ocular serious adverse events (SAEs) and no reported drug-related systemic SAEs in the 160 enrolled patients as of July 1, 2023.” Other reported findings include that DAVIO 2 patients had better starting visual acuity and less central subfield thickness (CST) than the phase 1 DAVIO cohort.

DAVIO 2 is a randomized, controlled phase 2 clinical trial of EYP-1901 in patients with previously treated wet AMD. All enrolled patients had been previously treated with standard-of-care anti-VEGF therapy and were randomly assigned to 1 of 2 doses of EYP-1901 (approximately 2 mg or 3 mg) or an aflibercept control.

Intraocular Corticosteroids Appear Superior for Recurrent Uveitis-related ME

■ Repeat treatment with corticosteroid injections improved vision in people with persistent or recurrent uveitis-related macular edema (ME) better than methotrexate or ranibizumab intravitreal injections, according to National Eye Institute‒funded clinical trial led by Nisha Acharya, MD, University of California San Francisco. The clinical trial enrolled 194 participants (225 study eyes) with well-controlled uveitis but persistent or recurrent macular edema. Sixty-five participants received a dexamethasone corticosteroid, 65 received methotrexate, and 64 received ranibizumab. The corticosteroid patients received 1 dexamethasone implant at baseline and, if the ME had not resolved, another at 8 weeks. The methotrexate patients received 1 injection at baseline and another at 4 and 8 weeks if ME did not resolve, and the ranibizumab group received injections at baseline, 4 weeks, and 8 weeks, even if ME resolved.

After 12 weeks, reduction in swelling was greatest in the dexamethasone group compared to the other 2 (35% reduction for corticosteroid; 20% for ranibizumab; 11% for methotrexate). In addition, the corticosteroid group showed improvement in vision of nearly 5 letters.

Adverum Completes Enrollment of Phase 2 LUNA Wet AMD Trial

■ Adverum Biotechnologies announced that it has completed enrollment in its ongoing phase 2 LUNA trial evaluating ixoberogene soroparvovec (Ixo-vec) for the treatment of wet AMD. The LUNA trial is a double-masked, randomized, phase 2 trial being conducted at approximately 40 sites in the United States and Europe. The corticosteroid regimens in LUNA were designed to cover the period of peak immunogenicity observed in nonclinical studies and in the phase 1 OPTIC study. This double-masked, randomized trial includes a primary cohort of approximately 60 subjects enrolled in the United States, and Adverum is maintaining the option to enroll an additional cohort of approximately 12 subjects. In a news release, Star Seyedkazemi, PharmD, chief development officer of Adverum said, “We believe Ixo-vec, with its previously demonstrated continuous expression of aflibercept over 3 years following a single, in-office intravitreal injection, has the potential to bring immense value to patients, caregivers, retinal specialists, payers, and health care systems.”

Kodiak Presents Status Update Following Clinical Trial Setback

■ Kodiak Sciences recently reported updates on tarcocimab for the treatment of diabetic macular edema (DME). The phase 3 GLEAM and GLIMMER trials did not meet their primary efficacy endpoints of noninferior visual acuity gains. Kodiak will wind down ongoing studies of tarcocimab, but future options for the tarcocimab program are still being evaluated. In a news release, Victor Perlroth, MD, Kodiak CEO, said, “Tarcocimab demonstrated what we see as industry-leading durability together with solid potency, but an unexpected increased rate of cataracts appears to have been the main driver to missing the primary efficacy endpoint in both studies.” The drug is designed to inhibit both IL-6‒mediated immune inflammation and VEGF-mediated angiogenesis and vascular permeability, and Kodiak plans to explore development of the drug as an unconjugated protein, as well as its bioconjugate form.

Théa Acquires ProQR’s RNA Therapy Ophthalmic Assets

■ ProQR Therapeutics announced that it will divest its late-stage ophthalmic assets, sepofarsen and ultevursen, to Laboratoires Théa. Within Théa, a fully dedicated team specializing in inherited retinal disorders and a new organization are being set up to manage these projects. Sepofarsen (QR-110) and ultevursen are investigational RNA therapies for treatment of Leber congenital amaurosis and Usher syndrome, respectively.

First International Retinoblastoma Liquid Biopsy Study Under Way

■ A liquid biopsy for detection of retinoblastoma has been developed by Jesse Berry, MD, director of ocular oncology and the retinoblastoma grogram at Children’s Hospital of Los Angeles. The hospital will lead an international liquid biopsy retinoblastoma study that will include samples from 18 centers. Children will be followed for a minimum of 2 years, so researchers can examine samples for possible cancer recurrence. In addition to diagnosis and determination of disease severity, the liquid biopsies offer genetic and chromosomal information, which gives a more complete picture of each child’s disease.

“We know that detecting a cancer as early as possible gives a child the best chance. In continuing to take biopsies from these children, we can treat any recurrences early on, even before they’re visible to a clinician upon examination,” Dr. Berry said in a news release.

Study Reveals Link Between GLP-1 Agonists and Diabetic Eye Disease

■ Diabetic patients treated with GLP-1 agonists, such as semaglutide (Ozempic; Novo Nordisk), had significantly more progression of existing diabetic eye disease compared with those treated with SGLT2 inhibitors such as Jardiance (empagliflozin), according to findings from a retrospective study performed by Stanford University researchers Ehsan Rahimi, MD, and colleagues. Dr. Rahimi presented the findings at the 2023 annual meeting of the American Society of Retina Specialists, in Seattle.

The analysis comprised 7,889 patients treated with GLP-1 agonists and 5,663 patients treated with SGLT2 inhibitors. All patients had existing nonproliferative diabetic retinopathy (NPDR). The GLP-1 group was almost twice as likely to progress to PDR after 3 years. Beginning at 6 months and continuing through 3 years, patients on GLP-1 agonists were significantly more likely to progress to DME. Researchers speculate that the GLP-1’s effect on HbA1c may play some role in the drug’s association with progression of existing diabetic eye disease.

Study Analyzes Accuracy of AI Answers to Patient Retinal Disease Queries

■ A cross-sectional study evaluating the accuracy and reproducibility of a chatbot’s responses to commonly asked patient questions about vitreoretinal disease revealed that current large language model–based platforms, such as chatbots, can provide largely inaccurate responses. Only 8 (15.4%) of 52 questions submitted initially by researchers were graded as completely accurate. After resubmission of the questions, all 52 responses were noted to have changed, with 26 responses (50.0%) materially changing. In 16 responses (30.8%), the accuracy materially improved, whereas in 10 responses (19.2%), the accuracy materially worsened. Some responses contained inappropriate or potentially harmful medical advice. In a research letter published in JAMA Ophthalmology, the study authors stated, “Many internet users seek health-related information, but most internet information comes from unregulated or unverified sources and may be unreliable,” and “Ophthalmologists need to be aware of the limitations and potential for dissemination of misinformation associated with these artificial intelligence (AI) platforms.”

Aflibercept Biosimilar SB15 Shows Safety and Efficacy for nAMD

■ An aflibercept biosimilar, SB15 (Samsung Bioepis), showed no clinically significant differences from aflibercept for the treatment of neovascular AMD in either outcomes or adverse events, according to a randomized double-masked, phase 3 multicenter trial. The study cohort was comprised of 224 patients in the SB15 biosimilar group and 225 patients in the aflibercept group. Patients received treatment every 4 weeks for the first 12 weeks, then every 8 weeks up to week 48, with final assessment at week 56.

There were no significant differences between the SB15 group and the aflibercept group in letters gained from baseline to 8 weeks (6.7 letters vs 6.6 letters, respectively) or from baseline to 32 weeks (7.6 letters vs 6.5 letters, respectively). At 32 weeks, both groups also showed similar improvements in central subfield thickness. Additionally, the SB15 and aflibercept groups showed similar incidences of treatment-emergent adverse events (TEAEs) and ocular TEAEs in the study eye and no significant between-groups differences in the incidence of intraocular inflammation.

Increased Medicare Spending Follows PE Acquisition of Retina Practices

■ Private equity acquisition of retina practices is associated with modest increases in Medicare spending and utilization, according to a retrospective analysis of 82 practices acquired by private equity (PE) and matched controls. Researchers used novel data on PE acquisitions of retina practices linked to the 20% sample Medicare claims data. Retina practices acquired by PE between 2016 and 2019 were matched to up to 3 non-PE (control) practices. Practices acquired by PE were compared to matched controls through 6 quarters after acquisition using a difference-in-differences event study design.

Relative to controls, PE-acquired retina practices increased the use of higher-priced anti-VEGF agents including aflibercept, which differentially increased by 6.5 injections per practice-quarter. As a result, Medicare spending on aflibercept differentially increased by $13,028 per practice-quarter, or 21%. The researchers concluded, “This finding highlights the need to monitor the influence of PE firms’ financial incentives over clinician decision-making and the appropriateness of care, which may be swayed by strong economic incentives.”

Infliximab May Improve Visual Acuity in PVR associated with RRD

■ Patients with proliferative vitreoretinopathy (PVR) experienced improved visual acuity after receiving an intravitreal injection of infliximab after pars plana vitrectomy, according to a phase 2, randomized, controlled study presented by Ayman Elnahry, MD, PhD, at the 2023 American Society of Retina Specialists annual meeting in Seattle.

The FIXER trial, performed by Dr. Elnahry and colleagues, evaluated intravitreal infliximab for the treatment of PVR associated with rhegmatogenous retinal detachment when given after pars plana vitrectomy and silicone oil injection. Thirty eyes received infliximab at the conclusion of pars plana vitrectomy, and 30 eyes did not receive infliximab. The primary outcome measure was final anatomic success, which was defined as complete retinal reattachment without tamponade at 6 months after silicone oil removal. The 30 eyes in the infliximab group and 29 eyes in the control group met the primary outcome measure of anatomic success. The final BCVA was better in the infliximab group than in the control group.

Consensus Survey on Fluocinolone Acetonide Implant for DME Published

■ To better understand the level of agreement among retina specialists on the role of inflammation in diabetic retinopathy (DR) and diabetic macular edema (DME), and the use of 0.19-mg fluocinolone acetonide (FAc) implant in DME treatment, a consensus survey was drafted and disseminated to retina specialists across the United States.

In total, 56 retina specialists completed the entire survey. In a paper published in Ophthalmic Surgery, Lasers Imaging Retina, the co-authors led by Anton M. Kolomeyer, MD, PhD, stated that they “highly agreed on the role of inflammation in pathophysiology of DR/DME, injection burden and patient adherence, and efficacy and safety of the FAc implant. However, full consensus was not found on the impact of the FAc implant on DR progression, FAc as baseline therapy for DME, and the effectiveness of the steroid challenge to mitigate intraocular pressure risk after FAc use.”

GALLEGO Phase 2 Trial Shows No Efficacy and High Rate of IOI

■ In the GALLEGO phase 2 trial to assess safety, tolerability, and efficacy of intravitreal injections of galegenimab (anti-HTRA1 Fab) in patients with geographic atrophy (GA) secondary to AMD, galegenimab showed no efficacy and a high rate of intraocular inflammation. This resulted in early study termination, according to David Eichenbaum, MD, who presented the GALLEGO findings at the 2023 annual meeting of the American Society of Retina Specialists.

Galegenimab was administered every 4 weeks or every 8 weeks for approximately 76 weeks in participants with GA secondary to AMD and compared with sham control. No statistically significant difference was observed in the mean change in GA area from baseline to week 72. Dr. Eichenbaum said, “While the ARMS2/HTRA1 genetic locus has been associated with risk of AMD development and progression, inhibiting HTRA1 with an anti-HTRA1 Fab in this study did not slow GA disease progression. Further research to better understand the role of HTRA1 in AMD is needed.”

Regenxbio Presents ABBV-RGX-314 Update at Annual ASRS Meeting

■ Regenxbio presented data on 3 phase 2 trials of ABBV-RGX-314, an investigational therapeutic for the treatment of wet AMD, DR, and other chronic retinal conditions. At the annual American Society of Retina Specialists, Ashkan M. Abbey, MD, presented on the pharmacodynamic study of ABBV-RGX-314 for nAMD, reporting that all cohorts demonstrated stable-to-improved BCVA and retinal thickness and that the majority of patients were injection-free in all cohorts, with meaningful reductions in anti-VEGF injection burden through month 6.

David S. Boyer, MD, presented on the suprachoroidal delivery of ABBV-RGX-314 in the AAVIATE study, reporting that treated patients had stable vision and retinal thickness, with a meaningful reduction in treatment burden across all dose levels at the 6-month mark. Dilsher S. Dhoot, MD, presented on the ALTITUDE study — ABBV-RGX-314 gene therapy for DR — reporting that, “A one-time, in-office injection of ABBV-RGX-314 gene therapy could potentially improve DR severity and reduce risk of vision threatening complications.” RP

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