Oxurion Presents THR-149 and THR-687 Clinical Trial Data

■ Oxurion released data on its KALAHARI (THR-149) and INTEGRAL (THR-687) diabetic macular edema (DME) studies at the Macula Society meeting in Berlin, during presentations made by Shree K. Kurup, MD, of University Hospitals in Cleveland, Ohio, and Francesco Bandello, professor and chairman of the department of ophthalmology, VitaSalute, Milan, Italy, respectively.

Dr. Kurup’s presentation on part A of the phase 2 study of THR-149 (KALAHARI), revealed that of the 3 intravitreal injections of THR-149 evaluated (0.01 mg, 0.04 mg, and 0.13 mg), in the high-dose group, a mean BCVA gain of 6.1 letters was seen at month 3, with gains observed up to month 6, as well as central subfield thickness stabilization over the 6-month study period compared to baseline, with no need for rescue treatment. Post hoc analysis, excluding 2 subjects with abnormalities on OCT, showed a mean gain in BCVA of 9.3 letters at month 3, which was maintained up to month 6.

Dr. Bandello reported on THR-687: the first part of the 2-part phase 2 INTEGRAL trial showed THR-687 to be safe and well tolerated with no serious adverse events and none of the patients requiring rescue medication through month 3. However, there was insufficient evidence of efficacy on the key endpoints — BCVA and central subfield thickness. As a result, Oxurion has decided not to advance THR-687 to part B of the INTEGRAL trial.

Researchers Identify Possible Link Between COVID Vaccine and Uveitis

■ The BNT162b2 mRNA COVID-19 vaccine might be associated with increased risk of noninfectious uveitis (NIU), according to a retrospective population-based study published in Ophthalmology. The study, which was performed by researchers affiliated with the department of ophthalmology at Lady Davis Carmel Medical Center in Haifa, Israel, analyzed data from 2,602,557 people who received 2 doses of the vaccine. A previous diagnosis of NIU was documented for 18,236 of those who received the first dose and 17,250 who received the second dose. Among patients with a history of uveitis there was an increased incidence of active NIU, in approximately 1 case per 1,000 vaccinated people. More than 90% of cases were anterior uveitis and treated topically.

The study suggests that the small estimated attributable risks suggest that the impact on public health is relatively minor. However, the authors state that ophthalmologists should be aware of this potential increased risk of relapse, and patients should be advised of the symptoms of active uveitis — particularly during the first 14 days following each dose.

The authors concluded, “While our results suggest an increased risk of uveitis among certain patient populations … the impact of this additional morbidity is outweighed by the reduced systemic COVID-19 morbidity achieved through vaccination.”

Apellis Submits NDA to FDA for Intravitreal Pegcetacoplan

■ Apellis Pharmaceuticals submitted a New Drug Application (NDA) to the FDA for intravitreal pegcetacoplan, a targeted C3 therapy for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD). Pegcetacoplan was granted Fast Track designation by the FDA, and the Agency’s decision on the NDA request is expected in August 2022.

The NDA submission is based on results from the phase 3 DERBY and OAKS studies at 12 and 18 months and the phase 2 FILLY study at 12 months. In the studies, treatment with both monthly and every-other-month pegcetacoplan resulted in a clinically meaningful reduction of GA lesion growth across a broad, heterogenous population of more than 1,500 patients. Pegcetacoplan demonstrated a favorable safety profile in all 3 studies. “We are now one step closer to our goal of bringing the first GA treatment to patients living with this relentless and irreversible disease,” said Jeffrey Eisele, PhD, chief development officer at Apellis, in a news release.

NIH Study Confirms Benefit of AREDS2 Formula for AMD

■ The Age-Related Eye Disease Studies — AREDS and AREDS2 — established that dietary supplements can slow progression of AMD. In a new report, scientists analyzed 10 years of AREDS2 data and showed that the AREDS2 formula, which substituted antioxidants lutein and zeaxanthin for beta-carotene, not only reduces risk of lung cancer due to beta-carotene but also is more effective at reducing risk of AMD progression, compared to the original formula. A report on the study, funded by the National Institutes of Health, was published in JAMA Ophthalmology.

The original AREDS study showed that a dietary supplement formulation (500 mg vitamin C, 400 international units vitamin E, 2 mg copper, 80 mg zinc, and 15 mg beta-carotene) could significantly slow the progression of AMD; however, 2 concurrent studies also revealed that people who smoked and took beta-carotene had a significantly higher risk of lung cancer than expected. “This 10-year data confirms that not only is the new [beta-carotene-free] formula safer, it’s actually better at slowing AMD progression,” said Emily Chew, MD, director of the division of epidemiology and clinical application at the National Eye Institute (NEI) and lead author of the study report, in a news release.

FDA Approves Beovu for the Treatment of DME

■ Novartis announced that the FDA has approved Beovu (brolucizumab-dbll) 6 mg for the treatment of DME. The approval was based on year 1 data from the phase 3 randomized, double-masked KESTREL and KITE studies, which met their primary endpoint of noninferiority in change in BCVA from baseline vs aflibercept at year 1.

In aggregate, a numerically lower proportion of patient eyes treated with Beovu had intraretinal fluid, subretinal fluid, or both at week 52 vs eyes treated with aflibercept: in KESTREL 60.3% in the Beovu arm vs 73.3% in the aflibercept arm; in KITE 54.2% in the Beovu arm vs 72.9% in the aflibercept arm. Through year 1, half of Beovu patients (55% in KESTREL and 50% in KITE) remained on a 12-week dosing interval following the loading phase. During this time, by week 52, patients received a median of 7 Beovu injections. Patients treated with Beovu demonstrated a significant reduction from baseline in central subfield thickness starting at week 4 and continuing to week 52.

“KESTREL and KITE were the first pivotal trials to assess an anti-VEGF on 6-week dosing intervals in the loading phase, suggesting Beovu may offer fewer injections from the start of treatment through year one. We look forward to offering a new treatment option to help address the unmet needs of patients with DME,” said Jill Hopkins, senior vice president and global development unit head of ophthalmology for Novartis, in a news release.

Development of Platform for Early Detection of Vision Loss Proceeds

■ Retina Technologies, Inc. (RetTech) announced that it is advancing the development of Ocuvue, a digital, modular vision screening platform that can be used remotely or integrated into any clinic. The platform allows for patients to get comprehensive vision screening exams and retinal images in 15 minutes and eliminates the need to move between multiple machines and testing rooms.

RetTech was founded by a team of medical students from the Icahn School of Medicine at Mount Sinai in New York, New York. Now RetTech is working closely with the New York Eye and Ear Infirmary (NYEE), part of the Mount Sinai Health System, to advance the development of Ocuvue. “I think the ability to get regular vision screening for early detection would be a big win-win for both doctors and patients,” said James C. Tsai, MD, MBA, president of NYEE and chair of the department of ophthalmology at Mount Sinai, in a news release.

Eyenuk’s Eyeart Algorithm Earns Kudos From UK Screening Committee

■ Eyenuk, Inc’s Eyeart v2.1 algorithm for autonomous diabetic retinopathy screening has been confirmed as safe and cost-effective for use in level 1 grading or as a filter prior to manual grading, and it has been identified as the only diabetic eye screening AI technology ready for live clinical implementation in the United Kingdom, according to a report developed by the UK National Screening Committee. The Eyeart system provides diabetic retinopathy (DR) detection in a single office visit during a diabetic patient’s regular exam. Once the patient’s fundus images have been captured and submitted to the Eyeart AI system, the DR detection results are available in a PDF report in less than 30 seconds. The Eyeart system is planned for use as part of a project that will use AI to address racial and ethical health inequalities, led by the Moorfields Eye Hospital NHS Foundation Trust in London, England.

Medical Student Ocular Cancer Fellowship Established

■ Research to Prevent Blindness (RPB) and Castle Biosciences have announced the establishment of the RPB/Castle Biosciences Medical Student Eye Research Fellowship in Ocular Cancer, which will award 1 fellowship to a medical student focusing on a research project related to ocular cancer. The fellowship, which must take place prior to the student’s third or fourth year of medical school, will be funded for 1 year with a $30,000 grant that will provide financial support in furtherance of the recipient’s ocular cancer research activities.

“While the types of cancers that our diagnostic tests address have expanded over the years, our commitment to patients, research, and innovation has remained the same, which is why we are proud to partner with RPB to offer this grant to a deserving student interested in making a difference in the field of ocular cancer,” said Derek Maetzold, president and chief executive officer of Castle Biosciences, in a news release.

Luxa Bio Doses First Participant in Phase 1/2a Dry AMD Trial

■ Luxa Biotechnology announced that the first participant has been treated in its phase 1/2a clinical trial of RPESC-RPE-4W for dry AMD, being conducted at the University of Michigan Kellogg Eye Center. The cell product being used in the clinical trial is a progenitor stage RPESC-RPE cell obtained after 4 weeks of differentiation. The RPESC-RPE-4W progenitor stage cell has shown increased engraftment and vision rescue compared to more mature RPE cell products.

Laboratory studies of RPESC-derived RPE cells demonstrated they could perform the critical repertoire of cell functions carried out by normal RPE cells, including trophic factor release and phagocytosis. Rajesh C. Rao, MD, the trial’s principal investigator, has transplanted 50,000 RPESC-RPE-4W cells under the macula of a study participant with advanced dry AMD. The phase 1/2a study will enroll up to 18 participants to assess the safety, tolerability, feasibility, and preliminary efficacy of subretinal RPESC-RPE-4W in a dose escalation, open-label study. The trial is cosponsored by the NEI of the NIH under a Regenerative Medicine Innovation Project cooperative agreement.

Study Demonstrates Effectiveness of Uplizna for Patients With NMOSD

■ Horizon Therapeutics announced data from its phase 3 pivotal trial of Uplizna in patients with neuromyelitis optica spectrum disorder (NMOSD) who have genetic variations. The data demonstrate the treatment’s effectiveness among patients with different genetic makeups, including those with certain variations associated with reduced response to conventional monoclonal antibody (mAb) therapies.

Treatment for NMOSD includes the use of mAbs that bind to and deplete the B cells that drive disease activity. Increasingly, therapeutic research has shown that genetic variations in the immune system can affect the efficacy of these mAb therapies. The phase 3 study found no significant differences in disease attacks or disability regardless of FCGR3A genotype. “These data illustrate how mechanistic precision in treatment design can help patients gain benefit from their regimen regardless of the genetic make-up of their immune systems,” Bruce Cree, MD, PhD, MAS, study author and professor of clinical neurology at the University of California San Francisco Weill Institute for Neurosciences, said in a news release.

Benefit of Corticosteroid Prior to Iluvien Confirmed by PALADIN

■ The phase 4 PALADIN study confirmed the benefit of using a course of corticosteroid prior to Iluvien to reduce the risk of intraocular pressure (IOP) spikes, according to Alimera Sciences. These results were presented at the annual ARVO meeting, by Christopher Fuller, MD, of Texas Retina Associates.

The 3-year PALADIN study evaluated the long-term safety and efficacy of Iluvien, a 0.19-mg fluocinolone acetonide (FAc) intravitreal implant, in patients with DME. The study enrolled 202 eyes in 159 patients with DME who had previously been treated with a corticosteroid and had not experienced a clinically significant rise in IOP. The eyes were treated with Iluvien, and patients were followed for up to 36 months. During the 36 months, the IOP distribution was marginally affected, with more than 96% of eyes showing a mean IOP ≤25 mmHg during any study visit.

Dr. Fuller concluded, “The steroid challenge pre-FAc is highly predictive of the IOP response post-FAc and not dependent on steroid choice or number of [dexamethasone implants]. This is evident by the small change in mean IOP of the full population and that 97% of eyes had IOP ≤25 mmHg over the 36 months post-FAc. Similarly, the steroid choice had little impact on visual acuity gains at 36 months with the full population experiencing significant vision improvement by nearly a line and eyes receiving a [dexamethasone implant] challenge were able to maintain vision.”

FDA Reviews Application for Lucentis Biosimilar

■ Coherus Biologics announced that the FDA has reviewed the Biologics License Application for Cimerli (ranibizumab-ranq), a Lucentis biosimilar, and the target for possible approval of the application is August 2022. The company also announced that it has discontinued development of CHS-305 (IBI-305), an Avastin biosimilar candidate, and is returning IBI-305 rights to Innovent Biologics. Last year, Coherus discontinued development of CHS-2020, an Eylea biosimilar.

“As we prepare for as many as 4 new product launches in 2022 and 2023, we continue to make strong progress transforming Coherus into an innovative immuno-oncology company supported by revenues generated by our diversified commercial portfolio of FDA-approved products,” said Coherus CEO Denny Lanfear in a news release. “Following the recent late-cycle review meeting with the FDA, we are finalizing our preparations to launch Cimerli later this year, if approved, into the $7 billion anti-VEGF ophthalmology market in the US,” he added.

Alimera Partner Begins Phase 3 Study of Iluvien in China

■ Alimera Sciences’ partner, Ocumension Therapeutics, received approval from the National Medical Products Administration for its investigational new drug (IND) application to begin a phase 3 clinical study of Alimera’s 0.19 fluocinolone acetonide intravitreal implant, Iluvien, in mainland China. The intent of the trial is to support a future NDA filing to gain marketing approval in China, with an equivalent indication to Alimera’s US indication, for the treatment of DME that was previously treated with a course of corticosteroids and did not have a clinically significant rise in IOP.

“We are very excited by the progress that Ocumension is making toward generating the data needed to seek approval in China for our intravitreal implant. We look forward to the start of the trial and to the subsequent data,” said Rick Eiswirth, Alimera’s president and CEO, in a news release.

Post Hoc Analysis of GATHER1 Zimura Data Presented

■ Iveric Bio announced a post hoc analysis from the GATHER1 clinical trial, which used enhanced OCT imaging to examine the effect of Zimura (avacincaptad pegol) on change in ellipsoid zone (EZ) integrity and growth of GA, and the correlation between fundus autofluorescence (FAF) and GA progression. The results showed that OCT-measured GA area strongly correlated with FAF-measured GA area, with minimal average differences in GA area between modalities. A 30% reduction was observed in OCT-measured GA growth with Zimura at 12 months, which is consistent with findings using FAF-measured GA growth in GATHER1. In addition, a 22% reduction in progressive EZ loss/attenuation at 18 months was observed with Zimura compared to sham. The data were presented at the Macula Society meeting, in Berlin, Germany, by Justis P. Ehlers, MD, from Cole Eye Institute of Cleveland Clinic. “This important study illustrates the potential for eye care providers to accurately diagnose and monitor patients who have GA with OCT alone, without additional equipment required,” said Christopher Simms, chief commercial officer for Iveric Bio, in a news release.

Nacuity Series B Financing Led by Foundation Fighting Blindness

■ Nacuity Pharmaceuticals announced the closing of $16.5 million in Series B financing led by Foundation Fighting Blindness and its venture arm RD Fund. Proceeds from the financing will be used to support the advancement of Nacuity’s clinical trials for NPI-001 and NPI-002 through proof of concept, as well as for general operations. Oral NPI-001 tablets are currently being evaluated in a phase 1/2 clinical trial, the SLO-RP study, in patients with retinitis pigmentosa associated with Usher syndrome. Nacuity expects to have interim results from this study in the second quarter of 2023. NPI-002, a proprietary sustained release antioxidant molecule designed to slow cataract progression delivered via intravitreal implant, is being evaluated in a phase 1/2 clinical trial that is currently enrolling patients undergoing vitrectomy in Australia. Nacuity expects to have results from this study in the second quarter of 2023, as well.

“This funding will help further our mission to develop a breakthrough treatment for retinitis pigmentosa and other serious blinding and chronic diseases caused by oxidative stress,” said Halden Conner, chairman, CEO, and cofounder of Nacuity Pharmaceuticals, in a news release.

Robot-assisted Subretinal Drug Delivery Performed in Human

■ The first-in-human study using a robotic device to assist in subretinal drug delivery in patients undergoing vitreoretinal surgery for macular hemorrhage was performed at the Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom. A dozen participants were recruited: 6 in a robot-assisted arm and 6 in a control manual surgery arm. The researchers explained in their American Journal of Ophthalmology report that subretinal hemorrhage was successfully displaced at 1 month postintervention, except for 1 control subject, and the median gain in visual acuity was similar in both arms.

All study subjects presented with acute loss of vision due to a subfoveal hemorrhage secondary to neovascular AMD. After standard vitrectomy, intraoperative OCT-guided subretinal injection of tissue plasminogen activator (TPA) was performed by either robot-assisted or conventional manual technique under local anesthesia. The robotic part of the procedure involved advancement of a cannula through the retina and stabilizing it during foot-controlled injection of up to 100 µL of TPA solution.

The study demonstrates the feasibility and safety of high-precision robot-assisted subretinal drug delivery, as part of the surgical management of submacular hemorrhage, simulating its potential future application in gene or cell therapy. RP