DARPin Fails to Get Approval Due to Inflammation

Wet AMD therapy had advantage of durability.

■ Allergan, an AbbVie company, and Molecular Partners, a clinical-stage biotechnology company developing a new class of custom-built protein therapeutics known as DARPin therapeutics, announced that the FDA has issued a complete response letter to the biologics license application (BLA) for abicipar pegol, a novel, investigational DARPin therapy with a fixed 12-week dosing period for patients with wet AMD. The letter from the FDA indicates that the rate of intraocular inflammation observed following administration of abicipar pegol 2 mg/0.05 mL results in an unfavorable benefit–risk ratio in the treatment of wet AMD. AbbVie plans to meet with the FDA to discuss their comments and determine next steps.

Allergan and Molecular Partners had made significant effort to bring down the high inflammation rate seen in the CEDAR and SEQUOIA phase 3 studies. In the MAPLE study, an open-label study that enrolled 123 wet AMD patients and evaluated the safety of the DARPin produced via a modified manufacturing process, the companies achieved improvement of inflammation rates for abicipar. In this single-arm study, treatment-naïve or prior anti-VEGF-treated patients received 3 monthly 2 mg abicipar injections followed by 2 mg injections every 8 weeks for up to a total of 5 injections through week 28.

As a result of the improvements in the manufacturing process, the companies reported that incidence of intraocular inflammation (IOI) was 8.9% in the MAPLE study, which was lower than the 15% rate observed in prior phase 3 studies. Most IOI events were assessed as mild to moderate in severity. The incidence of severe IOI was 1.6%, with 1 reported case of iritis and 1 reported case of uveitis. There were no reported cases of endophthalmitis or retinal vasculitis in this study.

“We continue to believe in the need for treatment options that provide patients with reliable vision gains and less frequent dosing for the treatment of nAMD,” said Michael R. Robinson, MD, vice president and global therapeutic area head of ophthalmology for AbbVie, in a news release. “We are committed to working with the FDA to determine the appropriate next steps for abicipar pegol.”

Cost-Benefit Analysis Shows Anti-VEGF Saves Money

Bevacizumab accounts for majority of savings.

■ Gary C. Brown, MD, MBA, of Wills Eye Hospital, led researchers who set out to determine the financial benefits of anti-VEGF therapy for wet AMD vs its cost to society. Financial factors are particularly important for anti-VEGF therapies, given that a separate 10-year study led by Sophie Bakri, MD, and presented at the 2020 virtual American Society of Retina Specialists meeting, showed that all 3 commonly used anti-VEGF therapies produced similar outcomes.

In the study by Dr. Brown, 11-year direct ophthalmic medical costs expended for bevacizumab, ranibizumab, and aflibercept monotherapies for 168,400 treatment-naive US patients were compared with ophthalmic and nonophthalmic direct medical, direct nonmedical, and indirect medical costs saved by the therapies. Bevacizumab monotherapy had an individual, 11-year $14,772 treatment cost and net $357,680 societal return (11-year 2,421% return on investment [ROI]). Ranibizumab therapy cost $106,582 and returned $265,870 to society (249% ROI), while aflibercept treatment cost $61,811 and returned $310,611 to society (503% ROI).

The 2018 wet AMD overall treatment cohort, 11-year net societal gain was $28.5 billion to patients and insurers, with $24.2 billion (84.9%) coming from bevacizumab therapy, $0.7 billion (2.5%) from ranibizumab therapy, and $3.6 billion (12.6%) from aflibercept therapy. Substituting bevacizumab for ranibizumab and aflibercept in the 2018 new-onset patients would potentially save an estimated $1.343 billion over 11 years. The researchers, who published their findings in the American Journal of Ophthalmology, concluded that bevacizumab, ranibizumab, and aflibercept monotherapies accrue considerable financial ROI to patients and insurers as they increase national wealth.

Regenxbio Plans Pivotal Trial in Gene-Derived Anti-VEGF

New data confirm efficacy, safety in wet AMD.

■ Armed with new 1-year data from its phase 1/2a trial confirming the efficacy and safety of gene-derived RGX-314 anti-VEGF therapy, Regenxbio said it would begin a pivotal trial of subretinal delivery in wet AMD later this year. In addition, the company said a phase 2, 40-patient AAVIATE trial of RGX-314 for wet AMD utilizing the SCS Microinjector is active and expected to dose the first patient this quarter. This targeted, in-office suprachoroidal delivery approach may provide additional options for patients in all settings of patient care. Regenxbio anticipates providing an interim data update from the first cohort in late 2020.

In the newly released 1-year data, patients in cohort 4 (n=12) and cohort 5 (n=11) demonstrated stable visual acuity with a mean BCVA change of +4 letters and -2 letters from baseline, respectively, as well as decreased retinal thickness, with a mean change in CRT of -61 µm and -79 µm, respectively.

There was a clinically significant and meaningful reduction in anti-VEGF treatment burden in both cohorts 4 and 5 compared to the treatment burden in the 12 months prior to RGX-314 administration. Patients in lower-dose cohort 4 received a mean of 4.1 injections over 1 year following administration of RGX-314, a 61% reduction in treatment burden. Patients in higher-dose cohort 5 received a mean of 1.4 injections over 1 year following administration of RGX-314, a reduction in treatment burden of 85%.

In cohort 4, 3 out of 12 (25%) patients received no anti-VEGF injections over 1 year, and these patients demonstrated a mean BCVA improvement of +6 letters and a mean reduction in CRT of -62 µm at 1 year. In cohort 5, 8 out of the 11 (73%) patients observed through 1 year have received no anti-VEGF injections after administration of RGX-314, and these patients demonstrated a stable mean BCVA change of 0 letters and a mean reduction in CRT of -95 µm at 1 year.

“Based on the overall results to date from the phase 1/2a trial, I believe that RGX-314 has the potential to profoundly impact all aspects of clinical management for patients with wet AMD,” said Robert Avery, MD, Founder of California Retina Consultants and Research Foundation and investigator surgeon in the phase 1/2a RGX-314 trial.

High-Dose Adverum Gene-Derived Anti-VEGF Excels in Trial

Cohort 1 patients go 15 months with no retreatment.

■ Adverum Biotechnologies said the 15 patients in high-dose cohorts 1 (n=6) and 4 (n=9) in the phase 1 OPTIC trial receiving gene-derived anti-VEGF (ADVM-022, aflibercept) have required no retreatments, with some patients going 15 months or beyond on a single intravitreal injection. In the lower-dose cohorts 2 (n=6) and 3 (n=9), some patients have required a small number of rescue injections. Across all cohorts, both BCVA and central retinal thickness have been maintained or improved.

Early evidence from cohort 4, consistent with that of cohort 3, suggests that a prophylactic regimen of steroid eye drops results in fewer adverse events and less inflammation, when compared to a prophylactic regimen of oral steroids as used in cohorts 1 and 2. In cohorts 3 and 4, no patients have required more than steroid eye drops.

Arshad M. Khanani, MD, MA, managing partner and director of clinical research, Sierra Eye Associates, clinical associate professor of ophthalmology, University of Nevada, and top enrolling investigator in the OPTIC trial said, “In my experience, the sustained anatomical treatment response following a single intravitreal injection of ADVM-022 is unprecedented, which is remarkable considering that the patients enrolled in OPTIC were difficult-to-treat and had previously required frequent injections to maintain their vision. The safety profile to date shows that ADVM-022 is well tolerated, and that the prophylactic steroid eye drop regimen has been effective at limiting early ocular inflammation. I believe that ADVM-022 has the potential to be a transformational gene therapy improving real-world outcomes for patients living with wet AMD.”

Adverum has also recently initiated a 33-patient trial of ADVM-022 in DME.

JCyte Cell Therapy for RP Effective in Trial

jCyte Inc. announced encouraging results from a phase 2b, multicenter clinical trial of jCell in retinitis pigmentosa (RP), irrespective of genetic subtype. A large and broad set of patients with RP and best-corrected visual acuity (BCVA) between 20/80 and 20/800 were randomized to treatment vs sham. Treatment consisted of a single intravitreal injection of either 3 million or 6 million human retinal progenitor cells (hRPC). The study evaluated changes in visual function and functional vision in subjects with RP who received a single jCell injection in comparison to a sham-treated control group.

The primary endpoint in the study was mean change in BCVA from baseline to month 12. Secondary endpoints included low light mobility, contrast sensitivity, kinetic visual fields, and a visual function questionnaire. The trial was specifically designed to learn more about the clinical effects of jCell therapy in a broad set of patients with RP to better understand 3 critical study variables: the optimal jCell dose, the performance of clinical trial endpoints in the study population, and the RP patient population likely to realize the most pronounced improvement from a single jCell treatment during the 12-month pivotal trial study period.

A total of 84 patients were randomized, of which 74 met criteria for the analysis. The mean change in BCVA from baseline to month 12 were +2.81, +2.96, and +7.43 letters in the sham (n=26), 3.0x106 hRPC (n=25), and 6.0x106 hRPC (n=23) treatment arms, respectively. Supportive improvements in the 6.0x106 hRPC target subgroup compared to the control (sham) group were also observed in all secondary endpoints, which further support the BCVA findings in this subpopulation. Adverse events were generally minor and transient. Based on these results, the company plans to advance jCell into a pivotal trial utilizing the data generated, which is supportive of both the efficacy and safety of jCell therapy in a broad set of RP patients.

FA Outperforms OCTA in Microaneurysm Diagnosis

Researchers from Milan, Italy, set out to compare fluorescein angiography (FA) and 5 different optical coherence tomography angiography (OCTA) devices and to test their reproducibility in the evaluation of retinal microaneurysms secondary to diabetic retinopathy (DR). Patients with DR were imaged on the same day with FA and 5 OCTA devices: prototype Spectralis OCTA (Heidelberg Engineering), prototype PlexElite (Zeiss), RTVue XR Avanti (Optovue), AngioPlex (Zeiss), and DRI OCT Triton (Topcon Medical). For all OCTA devices, a 3mm x 3mm volume scan pattern was performed. Microaneurysms were evaluated for the superficial capillary plexus (SCP) and deep capillary plexus (DCP).

Twenty eyes of 15 patients with DR were included. FA counted a significantly higher number of microaneurysms compared to OCTA devices. Spectralis OCTA obtained a significantly higher number of microaneurysms compared to PlexElite, RTVue XR Avanti, AngioPlex, and DRI OCT Triton. Higher sensitivity (43.3%) but lowest specificity (54.4%) was observed for Spectralis OCTA compared to other devices. The higher specificity (78.5%) and positive predictive value (83.3%) were observed for DRI OCT Triton. The researchers concluded that FA remains the best imaging modality to visualize retinal microaneurysms. The high variability between OCTA devices should be taken into account for future clinical trials as in clinical practice.

Ocugen Drug Has Received Orphan Status for 4 Indications

Ocugen said the FDA granted a fourth orphan drug designation for OCU400 in the treatment of PDE6B gene mutation-associated retinal diseases. Retinitis pigmentosa (RP) caused by PDE6B mutation is an inherited retinal dystrophy that leads to blindness by midlife and is characterized by the progressive loss of photoreceptors, with or without the loss of retinal pigment epithelium cells. At least 1 mutation in the PDE6B gene has been found to cause autosomal dominant congenital stationary night blindness, which is characterized by the inability to see in low light.

Clearside to Begin Clinical Trial for Wet AMD Drug

Clesrside Biomedical said the FDA has accepted its investigational new drug (IND) application for CLS-AX (axitinib injectable suspension), enabling initiation of a phase 1/2a clinical trial of CLS-AX in wet AMD patients by the end of 2020.

“The FDA’s acceptance of our IND submission for CLS-AX is a significant achievement for Clearside and demonstrates our ability to successful move another internally developed program into the clinic,” said George Lasezkay, PharmD, JD, president and CEO of Clearside, in a news release. “As a tyrosine kinase inhibitor (TKI), axitinib has demonstrated pan-VEGF inhibition in independent studies and may have the potential to be more efficacious than current, more narrowly focused VEGF inhibition approaches. In our internal preclinical studies, CLS-AX delivered through suprachoroidal injection was well tolerated and showed durability over several months, providing Clearside the opportunity to potentially reduce treatment burden and address a primary need for wet AMD patients. We look forward to initiating clinical work by the end of 2020.”

New PDS Phase 3 Data Show Excellent Durability

The Port Delivery System with ranibizumab (PDS) is a permanent, sustained-release, refillable, in-office eye implant, approximately the size of a grain of rice. This next-generation treatment from Genentech has the potential to maintain vision and alleviate treatment burden in wet AMD. Key findings from the phase 3, 415-patient ARCHWAY study include 98.4% of PDS patients going 6 months without needing additional treatment and maintained vision and retinal thickness at a level equivalent to patients receiving monthly ranibizumab eye injections, a current standard of care. Vision was also maintained at the key primary endpoints of 36 and 40 weeks. All patients were previously treated and responsive to anti-VEGF therapy.

Safety data from the study support a favorable benefit–risk profile for PDS. The PDS implant insertion surgery and refill–exchange procedures were generally well tolerated by patients, and the systemic safety of PDS was comparable to monthly ranibizumab injections. PDS could potentially reduce the number of treatments from 12 to 2 per year for wet AMD patients, without sacrificing efficacy. PDS is the first wet AMD therapy to achieve positive phase 3 results with this extended length of time of 6 months between treatments.

Iveric bio Begins Second Pivotal Trial in GA

Iveric bio announced the first patient has been dosed in the 400-patient GATHER2 trial, the second phase 3 clinical trial for Zimura (avacincaptad pegol), a novel complement C5 inhibitor, in development for the treatment of geographic atrophy (GA) secondary to AMD. The company announced previously that Zimura met its prespecified primary efficacy endpoint and reached statistical significance in GATHER1, the first phase 3 clinical trial for Zimura for the treatment of GA secondary to AMD. There are no US Food and Drug Administration or European Medicines Agency approved treatments available for patients with GA secondary to AMD.

"The absence of treatment options for geographic atrophy represents an area of urgent unmet medical need and a major public health concern for the expanding aging population," stated Glenn P. Sblendorio, CEO and president of Iveric bio. "The initiation of enrollment in GATHER2 brings us another step closer to potentially delivering a clinically meaningful therapy to patients with GA. The GATHER2 clinical trial, if positive, marks the second phase 3 clinical trial needed to seek regulatory approval for Zimura.”

"We believe GATHER1 is currently the only phase 3 clinical trial showing early suppression of GA growth, which continued for 18 months with continuous treatment," stated Kourous A. Rezaei, MD, chief medical officer of Iveric bio.

Home Monitoring Identifies Conversions Early

In an article recently published in the American Society of Retina Specialists (ASRS) member publication, Retina Times, authors presented electronic health record data that showed a 67% drop in new dry AMD patient office visits from March to May 2020 compared to the same time in 2019. The ForeseeHome AMD Monitoring Program (Notal Vision) provides remote, home-based monitoring for intermediate dry AMD patients at risk of converting to wet AMD.

Allen Ho, MD, director of retina research at Wills Eye Hospital in Philadelphia, Pennsylvania, presented real-world data on the performance of ForeseeHome at the American Society of Retina Specialists 2020 Virtual Annual Meeting. The data analysis showed that the use of ForeseeHome provided a significant benefit to patients by helping to detect their wet AMD earlier with better visual acuity, which is known to improve long-term visual outcomes through prompt anti-VEGF treatment.

Adverum Names New CEO as Trials Move Ahead

Laurent Fischer, MD, has joined Adverum Biotechnologies as its CEO and a member of the board of directors. Leone Patterson, who has served for 4 years in executive leadership roles at Adverum, most recently as the company’s CEO, will continue to be the company’s president. Adverum has thus far achieved positive results in a revolutionary phase 1 trial for single-injection, gene-derived anti-VEGF (aflibercept) as a one-time therapy for wet AMD.

“We are delighted to welcome an experienced industry leader of Laurent's caliber to our team at Adverum,” said Patrick Machado, JD, board chair of Adverum. “The skills that Laurent brings to our company as a physician and experienced public company CEO will be invaluable additions to our existing executive team, and set us up well for future success as we enter the next phase of our growth.” In related news, Adverum has completed dosing of cohort 4 (n=9) in its phase 1 OPTIC trial for wet AMD and begun dosing in its 33-patient phase 2 INFINITY trial for DME. Both trials employ a single-injection of gene-derived ADVM-022.

“The current gold-standard therapy for DME is burdensome and often not possible in clinical practice around the world, as patients require frequent, long-term anti-VEGF intravitreal injections,” said principal INFINITY trial investigator Arshad M. Khanani, MD, MA, in a news release.” Based on the transformative data presented to date in the ongoing OPTIC trial for wet AMD, I believe that, with a single intravitreal injection, ADVM-022 has the potential to change the treatment paradigm and improve outcomes for patients with DME.”

Anti-VEGF Therapies Show Efficacy Decline in Years 2 to 5

Of the two-thirds of Protocol T participants who completed a 5-year visit, mean visual acuity maintained improvement relative to baseline. However, visual acuity decreased from year 2 to year 5, although there was no associated change in retinal thickening. Whether other management strategies could have better maintained VA is unknown. These findings suggest that methods to improve long-term visual outcomes in eyes with DME are needed. These data were reported by Dante Pieramici, MD, of California Retina, at the American Society of Retina Specialists 2020 Virtual Annual Meeting.

Opthea Pan-Anti-VEGF and Eylea Effective in DME

At the recent American Society of Retina Specialists 2020 Virtual Annual Meeting, David Boyer, MD, reported that OPT-302 (Opthea) inhibits VEGF-C/-D, which may contribute to treatment resistance with VEGF-A suppression. This study assessed safety, vision, and anatomic outcomes of switching from anti-VEGF-A monotherapy to combination OPT-302 and aflibercept (Eylea; Regeneron) for persistent DME. This was off-label use. Combo group did better by +3 letters in BCVA, while 27% had greater than 10-letter gain in the combination group vs 0% in the aflibercept alone group. Conversion to combination OPT-302 with aflibercept was well tolerated with improved visual and anatomic outcomes in patients with persistent DME despite prior anti-VEGF-A monotherapy. Thus, dual-targeted inhibition of VEGF-C/-D and VEGF-A may hold promise in the management of DME.

Retina Specialists Consider Niche Use for Beovu

Despite the incidence of a small number of cases of irreversible vision-robbing retinal vasculitis, retinal vascular occlusion, and combined retinal vasculitis and occlusion that has been reported in connection with brolucizumab (Beovu; Novartis), retina specialists say the drug has apparently found a niche with some difficult-to-treat and well-consented wet AMD patients who require the superior drying ability that brolucizumab demonstrated in the HAWK and HARRIER studies.

In both phase 3 trials, ≥50% of patients achieved sustained dryness faster with brolucizumab (by weeks 8 and 4 in HAWK and HARRIER, respectively, and by weeks 12 and 8 with aflibercept [Eylea; Regeneron]). Additionally, ≥75% of patients reached sustained dryness faster with brolucizumab than those treated with aflibercept (by weeks 32 and 20 with Beovu 3 mg and 6 mg in HAWK and HARRIER, respectively, and by weeks 56 and 52 with aflibercept 2 mg).

Results also showed that following a 3-month loading phase, patients treated with brolucizumab required fewer injections to reach sustained retinal dryness, compared with aflibercept (an average of 3.3 and 2.6 injections with brolucizumab 3 mg and 6 mg in HAWK and HARRIER, respectively, and an average of 5.4 and 4.4 with aflibercept 2 mg).

Retina specialists caution that the drug should be stopped if any signs of inflammation occur. Read more recent brolucizumab news at https://www.retinalphysician.com/issues/2020/june-2020/beovu-gets-fda-label-update-with-warnings .

Asclepix Funds New Initiatives in Retinal Disease

Asclepix Therapeutics, Inc., a biopharmaceutical company that uses computational biology to identify potent peptide regulators of vascular homeostasis for the treatment of retinal and other important diseases, announced that it has closed a $35 million series A financing led by Perceptive Xontogeny Venture Fund, with participation from the Perceptive Life Sciences Fund. The proceeds from the financing will fund soon-to-begin phase 1/2a clinical trials of AXT107, the company’s lead investigational drug, for the treatment of DME, wet AMD, and macular edema secondary to RVO. AXT107 has a dual mechanism of action targeting VEGF and Tie2 and has preclinically shown long durability and unique drug delivery properties that may offer an improved treatment option for patients.

Lineage Cell Technologies Receives New Funding for OpRegen

Lineage Cell Technologies announced that as a result of continued clinical progress, the Israel Innovation Authority (IIA) has extended its previously awarded development grant in support of OpRegen, the company’s retinal pigment epithelium (RPE) cell transplant therapy in development for the treatment of dry AMD. The research and development grant of up to 9 million Israeli New Shekels (approximately $2.5 million) was awarded in 2019 by the IIA and has been extended for use through June 2021 based on promising clinical data from the ongoing phase 1/2a clinical study of OpRegen. The IIA has provided annual grants totaling approximately $16 million for the development of the OpRegen program so far.

"We are pleased that the IIA has elected to extend its financial support based on the positive momentum and clinical achievements we have demonstrated with our OpRegen program to date," stated Brian M. Culley, Lineage CEO. "We continue to generate promising data supporting the use of our RPE cells in dry AMD with geographic atrophy. Notably, after moving into patients with less advanced disease, we saw the first known finding of retinal tissue regeneration alongside reductions in the growth of geographic atrophy, and improvements in visual acuity and reading speeds in some patients.”

Quantel Completes Acquisition of Ellex

Quantel Medical has completed its acquisition of Ellex, including the company’s laser and ultrasound technology solutions (with the exception of 2RT and iTrack), via the financial holding company Lumibird Medical. The purchase includes the Ellex brand name, its research and development (R&D) and production site based in Australia, and its subsidiaries based in Australia, Japan, the United States, France, and Germany. The coming together of these 2 companies represents a milestone in their history. Quantel Medical and Ellex have a shared heritage in the development of cutting-edge technologies for the diagnosis and treatment of the leading causes of blindness worldwide: glaucoma, cataracts, age-related macular degeneration, and diabetic retinopathy.

The combination of Quantel Medical and Ellex offers major potential for growth and value creation through various synergies, including the sharing of R&D capacity and production sites, and the strengthening of their clinical work to meet the current and future needs of ophthalmologists. Quantel Medical and Ellex note that they have complementary strengths, in particular their product positioning, experience, and knowledge of the ophthalmology market. Bringing together the product portfolios of both companies will enable them to better meet the needs of healthcare professionals, in terms of both the applications and positioning of their ranges. In a related move, Ellex has spun off its iTrack MIGS portfolio into a dedicated glaucoma company, known as Nova Eye Medical and has acquired the Molteno3 glaucoma drainage device business from Molteno Ophthalmic Limited.

Clearside Establishes Blue-Ribbon Advisory Board

Clearside Biomedical has announced the formation of a scientific advisory board comprised of world-renowned retinal physicians to advise on the company’s research and development programs.

“Over the past year, we have been building awareness around the potential benefits of targeting treatment in the suprachoroidal space and working closely with retinal specialists to present data on this novel approach. These efforts have led to the formation of a group of leading retinal physicians who can provide real-world insights and validate the scientific rationale for our expanding pipeline programs,” said Thomas A. Ciulla, MD, MBA, chief medical officer and chief development officer of Clearside Biomedical, in a news release. The board consists of David Boyer, MD; David Brown, MD; Nancy Holekamp, MD; Carl Regillo, MD; and Peter Kaiser, MD.

“These physicians have collectively published at least a thousand scientific papers and are recognized thought leaders in the field of ophthalmology. We look forward to their guidance as we expand our research and clinical development strategy.”

“Clearside’s novel technology platform delivering proprietary pharmacologic agents to the suprachoroidal space may offer innovative new treatment options for our patients. My advisory board colleagues and I look forward to working with the Clearside team as they advance their research and development programs and explore new therapeutic targets,” added Dr. Kaiser.

Clearside says its proprietary SCS Microinjector targeting the suprachoroidal space offers unique access to the macula, retina, and choroid where sight-threatening disease often occurs. The company’s SCS injection platform is a flexible, in-office, non-surgical procedure, intended to provide targeted delivery to the site of disease.

Dataset Shows Steep Drop in Patient Visits During Pandemic

Vestrum Health announced that its continuously updated database confirms and documents that the COVID-19 pandemic has had a significant adverse impact on US retina practices and their patients. Patient volume suffered a severe decline, peaking at 50%, that began in the early weeks of the national shutdown, with a relatively greater decline in new-patient referrals relative to return-patient visits.

The volume of both returning patients and, in particular, new patients with the potentially blinding conditions of wet AMD, diabetic retinopathy, retinal detachment, and vitreous hemorrhage, declined precipitously and had not returned to baseline pre-COVID levels as of May 31, 2020. This implies that the pandemic and the response to the pandemic may result in a significant prevalence of undiagnosed and untreated vision threatening conditions and consequently permanent unrecoverable vision loss for many patients. The data suggest that presenting visual acuity in newly referred patients with DME during the COVID period has been worse than in pre-COVID times; this has implications regarding the physiological stress the pandemic may have on people with pre-existing disease and in particular for patients with delayed diagnosis and treatment.

Promising Early Results in Gene Therapy for XLRP

The Janssen Pharmaceutical Companies of Johnson & Johnson announced 6-month data from the ongoing phase 1/2 trial in collaboration with MeiraGTx that is investigating a gene therapy for the treatment of inherited retinal disease X-linked retinitis pigmentosa (XLRP). The interim data from a small number of patients showed that low and intermediate doses of the investigational adeno-associated virus retinitis pigmentosa GTPase regulator (AAV-RPGR) were generally well tolerated and indicated significant improvement in vision. Currently, there are no approved treatments for this condition.

The ongoing phase 1/2 clinical trial consists of 3 phases: dose escalation, dose confirmation, and dose expansion. In the dose-escalation phase (n=10), adults were administered low-dose, intermediate-dose, or high-dose AAV-RPGR. The primary endpoint of the trial is safety, with secondary endpoints assessing changes in visual function at prespecified timepoints after treatment.

In the dose-escalation phase, at 6 months, the low-dose (n=3) and intermediate-dose (n=4) cohorts demonstrated significant improvement from baseline in retinal sensitivity after treatment. Importantly, these improvements were evident when assessed with 2 perimetry approaches (static perimetry and microperimetry).

Bascom Palmer Again Tops in Ophthalmology

Bascom Palmer Eye Institute of the University of Miami Health System in Miami, Florida, has again been ranked again as the nation’s best in ophthalmology by U.S. News & World Report. This award represents the 19^th time and the 17^thconsecutive year that Bascom Palmer has received the number 1 ranking since the publication began surveying US physicians for its annual “Best Hospitals” rankings 31 years ago. Wills Eye Hospital of Thomas Jefferson University Hospital, in Philadelphia, Pennsylvania, came in second in the “Best Hospitals for Ophthalmology” list, followed by Wilmer Eye Institute of Johns Hopkins Hospital in Baltimore, Maryland; Massachusetts Eye and Ear Infirmary of Massachusetts General Hospital in Boston, Massachusetts; and Stein and Doheny Eye Institutes of UCLA Medical Center in Los Angeles, California.

Aerie Studies Steroid for Macular Edema Due to RVO

Aerie Pharmaceuticals reported positive top-line results for the company’s 49-patient phase 2 clinical trial evaluating AR-1105 (dexamethasone intravitreal implant) in patients with macular edema associated with retinal vein occlusion. The objective of the trial was to evaluate 2 formulations of AR-1105 with different steroid-release profiles. In the initial safety stage, 5 patients were enrolled in a single cohort to receive CF-1, delivering a 340-µg dose of dexamethasone in a single intravitreal injection. In stage 2, 44 patients were randomized 1:1 to receive either CF-1 or CF-2.

The results demonstrated positive and sustained treatment effects with both formulations as shown by increases in BCVA and reductions in macular edema. Peak efficacy was observed earlier with CF-1, while CF-2 demonstrated a longer overall duration of effect of up to 6 months.