New Updates on Gene-Derived Anti-VEGF
Adverum and Regenxbio continue to report positive early results.
■ The 2 companies advancing the concept of a single-injection, gene-derived anti-VEGF therapy for wet AMD both continue to report positive early-stage results. Adverum Biotechnologies reported that all 6 of the patients in the first cohort of its OPTIC phase 1 trial for ADVM-022 (aflibercept) have gone more than a year without needing a rescue injection, with some now out to 66 weeks. Regenxbio reported improved mean BCVA over a larger patient base with its RGX-314 (ranibizumab), although some patients did require rescue injections. For RGX-314, positive long-term efficacy signals continued over 2 years in the 6-patient cohort 3. The mean change in visual acuity across all 6 patients in Cohort 3 was markedly improved over 2 years, with a mean BCVA improvement of +14 letters. The mean change in CRT was stable, with an increase of +2 microns.
Adverum announced new interim clinical data from cohorts 1-3 of the OPTIC phase 1 dose-ranging clinical trial of ADVM-022 intravitreal (IVT) injection gene therapy in patients requiring frequent anti-VEGF injections for their wet AMD. Initial interim data were presented on a company call from 5 patients in the 9-patient cohort 3 and updated data presented from cohorts 1 and 2 following treatment with a single IVT injection of ADVM-022. ADVM-022 continues to show robust efficacy, with evidence of a dose response. In the higher-dose cohort 1, 6 of 6 patients have stayed rescue injection free. In the lower-dose cohorts 2 and 3, 8 of 11 patients remain rescue injection free.
Editor’s note: Read this story in its entirety at https://www.retinalphysician.com/issues/2020/may-2020/new-updates-on-gene-derived-anti-vegf
Clearside Announces Delay in Xipere NDA Submission
Company also licenses Xipere to Asian partner.
■ Clearside Biomedical has updated its timeline for its Xipere (triamcinolone acetonide suprachoroidal injectable suspension) NDA resubmission timeline and announced changes to its commercialization and development partnership with Bausch Health Companies. Xipere, a proprietary suspension of the corticosteroid triamcinolone acetonide formulated for suprachoroidal administration via Clearside’s proprietary SCS Microinjector, has completed a phase 3 trial as a targeted treatment of macular edema associated with uveitis.
The contract manufacturing organization (CMO) for Xipere has been completing certain requalification activities within its facility. While these manufacturing activities are not specifically related to Xipere, the CMO has advised Clearside that they continue to impact the timing of its production. As a result, and due in part to COVID-19 related challenges that have impacted work schedules, the CMO has informed Clearside that there will be a delay in completing the necessary corrective action. Clearside now expects to resubmit the Xipere NDA in the fourth quarter of 2020.
In conjunction with this update, Clearside and Bausch Health have amended and revised their partnership for Xipere. Bausch + Lomb acquired an exclusive license in October 2019 for the commercialization and development of Xipere in the United States and Canada. Bausch + Lomb has now been granted exclusive options for the right to commercialize and develop Xipere in (1) Europe and the United Kingdom, (2) Australia and New Zealand, and (3) South America and Mexico. In the amended agreement, Bausch + Lomb has extended the time allowed for Clearside to obtain Xipere approval in the United States.
Clearside Biomedical has also announced that Arctic Vision, a company focused on developing and commercializing innovative ophthalmology therapies in China and Asia, has acquired an exclusive license for the commercialization and development of Xipere in Greater China (including mainland China, Hong Kong, Macau and Taiwan) and South Korea.
Research and industry news in retina.
BY JERRY HELZNER, CONTRIBUTING EDITOR
Assessing Possible Damage From Intravitreal Injections
■ In a groundbreaking study, researchers from Mount Sinai Hospital in New York are using OCT angiography (OCTA) to measure potential retinal damage from long-term use of intravitreal eye injections. The findings, published in the journal Retina, suggest that repeated injections could contribute to progressive vision loss after many years. The results may also lead to changes in the way eye conditions are treated.
“These injections cause eye pressure to temporarily go up 3 times normal levels, and while patients typically recover within minutes, we wanted to know the immediate impact on blood flow to the eye,” said senior investigator Richard Rosen, MD, of the Department of Ophthalmology at the Icahn School of Medicine at Mount Sinai.
Using OCTA, the researchers analyzed the eyes of 39 patients over age 18 after they received intravitreal bevacizumab or aflibercept injections for diabetic retinopathy, macular degeneration, choroidal neovascular membrane, retinal vein occlusion, or radiation retinopathy. Minutes after the injections, the researchers measured blood flow in different areas of the macula and optic nerve. On average, they found a significant and temporary spike in eye pressure along with a significant and temporary reduction of blood flow that eventually resolved. They discovered that some areas of the macula and nerve were stressed more than others, and this newfound information can lead doctors to use advanced imaging and visual field testing to look for early signs of damage.
“If patients are receiving monthly injections that repeatedly stress the eye, we may have to start looking for signs of cumulative damage,” noted lead author Alexander Barash, MD, clinical assistant professor of ophthalmology at The New York Eye and Ear Infirmary of Mount Sinai.
Lipids a New Way to Deliver Gene Therapy
■ Researchers at Case Western Reserve University have used a unique method to safely deliver gene therapy to treat Stargardt disease. By using chemically modified lipids instead of the viruses most commonly used as carriers, Stargardt disease did not return in animal models for up to 8 months after treatment, said lead researcher Zheng Rong Lu, professor of biomedical engineering at the Case School of Engineering, with a dual appointment at the School of Medicine.
“Because [lipids] are basically unsaturated oil, the likelihood of damage to the eye is low, which isn’t always true with the viral gene therapy,” Lu said in a news release.
The most successful gene therapy carriers so far have been certain viruses (the AAV, or adeno-associated virus, especially) because they can deliver the new gene by “infecting” the target cell. But the Stargardt-associated gene, known as the ABCA4 gene, turns out to be too large to fit within that popular virus, Lu said.
Lu said other researchers have attempted to remedy that problem by splitting ABCA4 into pieces and then trying to reassemble it inside the eye — with limited success. Lu’s research was recently published in the journal Molecular Therapy.
Verana Health Will Handle End-to-End IRIS Registry Administration
■ The AAO said Verana Health, the data curation and analytics partner of the American Academy of Ophthalmology IRIS Registry, will serve as the end-to-end data and technology partner for the IRIS Registry moving forward. This announcement represents a significant expansion of the Verana Health and AAO relationship, with Verana Health assuming responsibility for EHR integration, practice support, and MIPS quality reporting for physicians contributing to the IRIS Registry.
Verana Health was selected as the Academy’s new end-to-end data and technology partner for the IRIS Registry to offer an enhanced physician experience that is highly reliable and responsive to requests and inquiries, provide MIPS reporting with the highest degree of quality, and ensure the exceptional data quality required to provide the ophthalmic community with meaningful insights and technology applications. Applications of this high-quality data include more robust practice performance and benchmarking capabilities.
Early Detection of Second Eye Wet AMD Spurs Better Outcomes
■ Nancy Holekamp, MD, initiated a study of her own patients to determine whether monthly OCT imaging of at-risk, asymptomatic fellow eyes could detect an early presence of wet AMD that would lead to earlier treatment and better visual outcomes. Out of 50 patients (18 male and 32 female), the mean visual acuity of first-eye diagnosis was 20/68, while the mean visual acuity of the second eye at diagnosis was 20/30. The mean visual acuity of first eye at 12 months was 20/53, while the second eye remained at mean visual acuity of 20/30 at 12 months. The number of anti-VEGF injections was somewhat fewer for the second eye at 12 months, but did not reach statistical significance. Follow-up continued for a mean of 59 weeks for the first eye and 38 weeks for the second eye, with the second eye maintaining better visual acuity.
Dr. Holekamp concluded that monthly OCT of the fellow eye is effective in early detection of wet AMD but burdensome to the practice and patient. She suggested that home OCT could play an important role in achieving early detection of wet AMD. This research was presented at ARVOLearn 2020. RP