SUBSPECIALTY NEWS: FDA approves Cimerli, GATHER2 GA trial meets primary endpoint, and more.
FDA Approves Cimerli, the First Biosimilar to Lucentis
■ Coherus Biosciences announced that the FDA has approved Cimerli (ranibizumab-eqrn) as a biosimilar product interchangeable with Lucentis (ranibizumab; Genentech), for all 5 indications: wet AMD, macular edema following RVO, DME, DR, and myopic choroidal neovascularization, meeting the FDA’s standards to the reference product, including safety, efficacy and quality. Commercial availability of Cimerli, in both 0.3 mg and 0.5 mg dosages, is planned for October 2022.
The approval of Cimerli and its determination of interchangeability with Lucentis is based on a comprehensive program, including the COLUMBUS-AMD study, to confirm equivalent safety and efficacy to Lucentis. The COLUMBUS-AMD study met its primary endpoint of change from baseline in BCVA at week 8 compared to reference ranibizumab. Secondary endpoints included change from baseline in BCVA at 48 weeks, change from baseline in FCB retinal thickness at 48 weeks, safety, and immunogenicity.
“As a practitioner committed to the safety and well-being of patients, having an approved biosimilar product that is interchangeable with Lucentis — with a similar safety and efficacy profile — is great news for patients,” Peter K. Kaiser, MD, professor of ophthalmology at the Cole Eye Institute of Cleveland Clinic, and an advisor to Coherus, said in a news release.
Zimura GATHER2 GA Phase 3 Trial Data Announced
■ Iveric Bio announced that GATHER2 met its primary endpoint of mean rate of growth (slope) in geographic atrophy (GA) area at 12 months, with statistical significance and a favorable safety profile. GATHER2 is the second phase 3 clinical trial evaluating Zimura (avacincaptad pegol), a novel investigational complement C5 inhibitor, for the treatment of GA.
A total of 448 participants were enrolled in this double-masked, sham-controlled study measuring the efficacy and safety of monthly 2 mg intravitreal Zimura, in patients with GA. For the first 12 months, patients were randomized to receive either Zimura 2 mg or sham monthly. At 12 months, participants in the Zimura arm were re-randomized to either receive Zimura 2 mg once monthly or every other month until month 23 of the study. The final evaluation will take place at month 24. The slope in GA area was measured by fundus autofluorescence (FAF) based on readings at baseline, month 6, and month 12, and was calculated using the square root transformation of the GA area. There were no events of endophthalmitis, no intraocular inflammation events, and no ischemic optic neuropathy events through month 12. The incidence of choroidal neovascularization (CNV) in the study eye through month 12 was 15 patients (6.7%) in the Zimura 2 mg group and 9 patients (4.1%) in the sham control group.
“We are thrilled to see for the first time an investigational therapy with a statistically significant reduction in the rate of GA progression at the 12-month primary endpoint across 2 phase 3 clinical trials. The results from GATHER1 and GATHER2 and our Special Protocol Assessment (SPA) with the FDA provide the basis for an NDA, which we are planning to submit by the end of first quarter of 2023,” Glenn P. Sblendorio, CEO of Iveric Bio, said in a news release.
OliX Gets FDA Go-ahead to Develop RNAi Therapeutic for AMD
■ OliX Pharmaceuticals announced that the FDA has approved the company’s IND application to develop OLX10212 for the treatment of AMD. OLX10212 targets inflammation pathways that play a key role in the development of GA and neovascular AMD. The primary objective of the phase 1 study is to evaluate the safety and tolerability of OLX10212 in patients with AMD.
“FDA approval of the IND for OLX10212 marks a significant milestone in expanding OliX’s commitment to the treatment of ophthalmic diseases. Based on OLX10212’s encouraging preclinical data, we believe it holds promise to become a novel, safe, and efficient treatment option for patients with GA and neovascular AMD,” Dong Ki Lee, PhD, founder and CEO of OliX Pharmaceuticals, said in a news release.
Paladin Phase 4 Study Confirms ILUVIEN Safety for DME
■ Alimera Sciences announced that the PALADIN phase 4 study confirms the safety of the Iluvien (fluocinolone acetonide [FAc] intravitreal implant 0.19 mg) sustained-release intravitreal implant and provides a durable treatment option that reduces the frequency of recurrence for patients with DME. The study confirms the benefit of using a prior course of corticosteroid to mitigate the risk of uncontrolled IOP elevations, as well as the reported secondary outcomes of vision improvement and reduction in treatment burden and retinal thickness variability.
Among the study findings: Eyes were undertreated during the 3 years prior to administration of Iluvien and lost on average 6.4 ETDRS letters during that time. Following administration of Iluvien, eyes gained 4.5 ETDRS letters on average and treatment frequency was reduced to 1.7 mean yearly treatments. Significantly more eyes achieved a CST ≤300 µm following FAc administration compared to baseline, and eyes experienced significantly less retinal thickness variability post-FAc treatment, which correlated to improved visual outcomes and better disease control.
“The data verify that Iluvien provides physicians with a much-needed tool for safe and durable treatment of DME,” Christopher Riemann, MD, a vitreoretinal surgeon at the Cincinnati Eye Institute, said in a news release.
Avista and Roche Partner on Gene Therapy for Ocular Disease
■ Avista Therapeutics, a company involved in development of gene therapies for rare ophthalmic conditions, announced a partnership with Roche to develop novel adeno-associated virus (AAV) gene therapy vectors for the eyes. The partnership aims to apply Avista’s single-cell AAV engineering (scAAVengr) platform technology to develop intravitreal AAV capsids matching a capsid profile defined by Roche. The plan also entails development of a proprietary pipeline built on a toolkit of AAV variants that can target gene delivery to individual retinal cell types. Roche will be responsible for conducting preclinical, clinical, and commercialization activities for gene therapy programs using these novel capsids, which will be distinct from Avista’s internal pipeline.
Avista’s computationally guided, in vivo scAAVengr platform leverages a high-throughput approach with built-in quantitative validation of novel cell-specific AAVs, enabling the rapid translation of transformative gene therapies to the clinic for diseases impacting people’s vision.
“We are excited to enter into this collaboration with Roche. This collaboration will complement our in-house pipeline and will accelerate the delivery of transformative therapies to patients,” Robert Lin, PhD, chief executive officer of Avista Therapeutics, said in a news release.
Clearside Completes Dosing Phase of OASIS Wet AMD Trial
■ Clearside Biomedical announced that it has completed dosing in cohorts 3 and 4 of OASIS, its phase 1/2a clinical trial of CLS-AX (axitinib injectable suspension) in patients with wet AMD. The study enrolled 8 patients in cohort 3, and 8 patients in cohort 4, all of whom received aflibercept at their first visit and a single dose of CLS-AX at their second visit 1 month later. In total, there were 27 patients in 4 cohorts enrolled in OASIS, with escalating doses of CLS-AX: cohort 1 at 0.03 mg (n=6); cohort 2 at 0.10 mg (n=5); cohort 3 at 0.50 mg (n=8); and cohort 4 at 1.0 mg (n=8). The primary endpoint for the trial will assess the safety and tolerability of CLS-AX for 3 months.
“The completion of enrollment in OASIS is a critical milestone as we look forward to our data readout from the full OASIS trial in the fourth quarter of this year,” Thomas A. Ciulla, MD, MBA, chief medical officer and chief development officer of Clearside Biomedical, said in a news release.
First Patient Dosed in Eyepoint’s EYP-1901 Wet AMD Trial
■ Eyepoint Pharmaceuticals announced that the first patient has been dosed in the phase 2 “Durasert and Vorolanib in Ophthalmology 2” (DAVIO 2) clinical trial of EYP-1901, an investigational sustained-delivery anti-VEGF treatment for wet AMD. The 12-month, randomized, controlled study is expected to enroll approximately 150 patients, previously treated with a VEGF therapy, randomly assigned to 1 of 2 doses of EYP-1901 (approximately 2 mg or 3 mg) or an aflibercept control. The primary efficacy endpoint of the DAVIO 2 trial is change in BCVA compared to the aflibercept control 6 months after the EYP-1901 injection. Secondary efficacy endpoints include change in CST, time to first supplemental anti-VEGF, and safety.
“We are encouraged by the safety and efficacy results from our phase 1 DAVIO trial, including no reports of ocular or drug related systemic serious adverse events and strong durability data with 53% of patients requiring no supplemental treatment up to 6 months. We anticipate initial top-line data from our phase 2 trial in the second half of 2023,” Nancy Lurker, Eyepoint CEO, said in a news release.
First Patient Dosed in Ocuterra OTT166 Phase 2 Diabetic Retinopathy Trial
■ Ocuterra announced the first patient was dosed in its phase 2 DR:EAM (Diabetic Retinopathy: Early Active Management) clinical trial evaluating OTT166. DR:EAM is a multicenter, randomized, double-masked clinical trial to assess the safety and efficacy of a high and low dose of daily topical OTT166 vs placebo for 24 weeks in approximately 200 adult patients with moderately severe to severe NPDR or mild proliferative DR with minimal vision loss. OTT166 is a novel small-molecule selective integrin inhibitor that is designed to reach the retina from eye drop application. The primary efficacy endpoint of the clinical trial is the percentage of patients that have a 2-step improvement in the Diabetic Retinopathy Severity Scale (DRSS).
OTT166 was designed to be administered as an eye drop by the patient at home before DR has advanced to a vision-threatening complication, such as DME. “OTT166 has demonstrated tolerability and promising evidence of biological activity in patients in a phase 1b clinical trial and we believe that it has the potential to dramatically change the treatment paradigm by enabling earlier, noninvasive, active treatment for patients with diabetic retinopathy if approved,” said Kerrie Brady, chief executive officer and president of Ocuterra Therapeutics.
Kiora’s KIO-301 Retinitis Pigmentosa Drug Gets Go-ahead for FDA Phase 1 Trial
■ With the help of Harrington Discovery Institute at University Hospitals, Kiora Pharmaceuticals has been granted approval to start a phase 1b, first-in-human clinical trial of small molecule KIO-301 administered intravitreally. KIO-301 was initially developed by Richard Kramer, PhD, at the University of California, Berkeley. As part of the Harrington Project for Discovery and Development, Harrington Discovery Institute aims to advance medicine by enabling scientists to turn their discoveries into medicines that improve human health.
In patients with retinitis pigmentosa, photoreceptors are no longer viable and therefore their downstream signal relaying cells, retinal ganglion cells (RGCs), are not capable of being activated. KIO-301 preferentially enters these RGCs and turns them into light sensing cells. KIO-301 achieves this by lodging inside specific voltage-gated ion channels.
“When we look at the world, we’re constantly moving our eyes and need to respond to changes of light, not just the presence or absence of it. The drugs we developed are light sensitive and have the potential to restore clinically meaningful vision,” Dr. Kramer said in a news release.
Lumithera Announces Purchase of Maculogix Assets
■ The photobiomodulation treatment company Lumithera announced the purchase of Maculogix assets by its wholly owned subsidiary. Maculogix is the developer of the wearable Adaptdx Pro dark adaptometer, which enables measurement of dark adaptation for early diagnosis of dry AMD.
Maculogix leverages the science of dark adaptation through its Adaptdx and Adaptdx Pro guided by Theia, dark adaptation functional testing technology, that enables eye-care professionals to detect, monitor, and treat AMD 3 years before it can be seen clinically. The core technology measures the inability to visually adapt to low levels of light, a key clinical marker seen in patients with early AMD. Dark adaptation technology has been validated in 42 peer-reviewed papers.
“Adaptdx Pro can identify dry AMD patients at the earliest timepoint, in advance of pathology, and before vision loss. We are excited to combine diagnosis, treatment, and monitoring platforms to provide a complete solution for dry AMD patients,” Clark E. Tedford, PhD, president and CEO of Lumithera, said in a news release.
The Lumithera announcement follows the release of its positive 13-month US LIGHTSITE III treatment data in intermediate dry AMD patients treated with the Valeda Light Delivery System.
Consensus on Risk Mitigation for Brolucizumab in Wet AMD Published
■ A consensus document on the use of brolucizumab for nAMD written by an international cadre of retina specialists was published in the September issue of Retina (doi: 10.1097/IAE.0000000000003556). The report, which aims to provide guidance on the use of brolucizumab for neovascular AMD, is based on the authors’ opinions and a review of relevant literature. The authors stated, “Brolucizumab has high efficacy in retinal fluid resolution and provides the possibility for longer dosing intervals in the treatment of nAMD. However, brolucizumab has been associated with events of retinal vasculitis and retinal vascular occlusion typically in the presence of other signs of intraocular inflammation (IOI).”
The literature review was conducted on adverse events related to IOI after administration of brolucizumab in eyes with wet AMD. The researchers found, “Possible risk factors for IOI and retinal vascular occlusion after brolucizumab should be considered before administering brolucizumab. Patients who receive brolucizumab should be educated on the symptoms, signs, and time course of IOI after brolucizumab. Before each injection of brolucizumab, physicians should assess the eye for any signs of inflammation and not treat with brolucizumab if inflammation is detected. Treatment of IOI should be prompt and provided with particular attention to the posterior segment.”
Proqr to Focus on RNA Editing and Identifying a Strategic Partner
■ Proqr Therapeutics provided an update on its ophthalmology programs following feedback from the European Medicines Agency (EMA) related to sepofarsen. It will now focus exclusively on its Axiomer RNA-editing technology platform, and it will seek a strategic partner to take its ophthalmology portfolio forward.
Following the results from the sepofarsen ILLUMINATE trial, the EMA has recommended an additional clinical trial be conducted for sepofarsen prior to submitting a Marketing Authorization Application. In light of this feedback and to continue advancement of the portfolio of ophthalmic product candidates, including sepofarsen for LCA10 and ultevursen (QR-421a) for USH2A-mediated Usher syndrome and retinitis pigmentosa, Proqr will seek a strategic partner. Until a partner is found that can fund the clinical programs moving forward, the current ongoing trials of sepofarsen and ultevursen will be wound down. For people currently participating in these trials, Proqr will offer continued access to currently available sepofarsen or ultevursen.
“As we prioritize the development of our Axiomer RNA-editing platform technology, we believe partnering our ophthalmology assets is the best strategy to drive these programs forward to patients,” Daniel A. de Boer, CEO of Proqr Therapeutics, said in a news release. RP
Laser Retinopexy Offered Best Outcomes for Children With Retinal Detachment
The prevalence of rhegmatogenous retinal detachment (RRD) in children increases with age, and treatment techniques vary throughout the United States, according to Yoshihiro Yonekawa, MD, a pediatric retina specialist at Wills Eye Hospital in Philadelphia. Dr. Yonekawa presented these findings in July at the annual meeting of the American Society of Retina Specialists in New York.
Dr. Yonekawa and colleagues analyzed the electronic health records of children with RRD from the Vestrum Database. A total of 2,200 children from all geographic US regions, with an average age of 12 years, were included in the study, which covered the period from January 2015 to August 2021. The researchers found that the prevalence of RRD increased with age (P=.009) and the most common ocular comorbidities among children in the study were myopia (34.6%), ocular trauma (15%), and history of prematurity (11.5%). Timing of intervention varied, but the intervention was performed within 1 week in 55.4% of cases. Laser retinopexy was used as initial treatment in 23.3% of children and resulted in the best mean visual acuity (VA) at 1 year (20/32). Primary scleral buckling was performed in 33.3% of cases and resulted in the second highest mean VA (20/63). Primary vitrectomy was used in 21.5% of cases and resulted in the lowest mean VA (20/200).
Ihealthscreen Advances AI Platform for AMD Screening and Stroke Prediction
The company Ihealthscreen Inc. announced that it completed a prospective study of Ipredict, its artificial intelligence–based platform for early diagnosis of age-related macular degeneration (AMD), in primary care settings. The initial clinical trial results show adequate accuracy for US Food and Drug Administration (FDA) clearance. The study was funded with a Small Business Innovation Research (SBIR) grant in partnership with the National Institutes of Health (NIH) and completed with the collaboration of the New York Eye and Ear Infirmary at Mount Sinai. Ihealthscreen is in the final stage of submitting the results to the FDA for 510k clearance. “We are encouraged by the results and believe that the new AI-based technology can diagnose early AMD in primary care settings, which enables timely measures by ophthalmologists to prevent deterioration of vision,” Alauddin Bhuiyan, PhD, the chief executive officer (CEO) of iHealthScreen, said in a press release.
In related news, Ihealthscreen introduced Ipredict’s automated stroke prediction model, which offers an overall accuracy of 82.4% for identifying an individual at risk of having an incident stroke within 5 years. The automated Ipredict platform achieved higher accuracy than existing stroke prediction models, such as Framingham (64.9%) and CHADS2VASC scores (63.8%). These results were presented in March at the Society for Brain Mapping and Therapeutics World Congress in Los Angeles.
Pixium Moves Forward With Wireless AMD Implant and Remote Monitoring
Pixium Vision announced the successful implantation of its wireless implant in the first patient in the Netherlands, in the pivotal PRIMAvera atrophic dry AMD trial.
“This successful implantation follows approval of the PRIMAvera study by the Dutch Ministry of Health, Welfare and Sport and the opening of the first PRIMAvera clinical site in the Netherlands, at the Rotterdam Eye Hospital. A total of 38 patients will be enrolled in the PRIMAvera study, an open-label, baseline-controlled, nonrandomized, multicenter, prospective, single-arm pivotal trial. The potential of the technology and the relative ease with which the small wireless implant can be surgically placed under the macula offer a real chance for patients who lost vision due to dry AMD and we look forward to contributing further to the PRIMAvera study,” Dr. Koen van Overdam, consultant ophthalmologist and vitreoretinal surgeon at the Rotterdam Eye Hospital, said in a news release.
In related news, Pixium announced the approval of a remote rehabilitation system for patients enrolled in the PRIMAvera pivotal trial and the French Feasibility Study in atrophic dry AMD. This platform allows AMD implant patients to conduct rehabilitation sessions from home, with or without the help of a family member or a caregiver, and requires only a digital tablet, provided by Pixium, and an internet connection.
Intermittent Fasting Associated With Decreased Risk of AMD
Skipping breakfast appears to have a protective effect against the development of AMD, according to the findings of a study published in July by the American Journal of Ophthalmology. This cross-sectional study utilized population-based, government-led survey data from the Korean National Health and Nutrition Examination Survey (KNHANES). Researchers from Yonsei University College of Medicine in Seoul, Korea, demonstrated that intermittent fasting by skipping breakfast was significantly associated with a reduced risk of AMD particularly in individuals who were less than 70 years of age, were obese, or resided in an urban area.
A total of 4,504 subjects ≥55 years of age from the KNHANES 2015-2018 database were divided into 2 groups based on breakfast frequency per week: intermittent fasting (nearly 0 time/week) and nonfasting (5-7 times/week). The study identified AMD in 25.1% of total subjects.
Multiple logistic regression analysis was performed to determine the risk factors for AMD identified by fundus photography. The intermittent fasting group had a decreased risk of AMD compared to the nonfasting group. Increased age and serum high-density lipoprotein (HDL) levels were also identified as independent risk factors for AMD.
Opthea Successfully Closes Financing Deals to Support OPT-302
Opthea Limited announced that it has received binding commitments from investors to raise approximately $90 million, and has entered a nondilutive financing arrangement for up to $170 million with Carlyle and Abingworth, in collaboration with their recently formed development company Launch Therapeutics. The proceeds will be used to continue advancing phase 3 clinical trials of OPT-302 for the treatment of neovascular AMD through topline data readout; to fund precommercialization activities, including commercial-scale manufacturing, team build, and market shaping; and to provide additional working capital beyond the phase 3 trial topline data readout. OPT-302 is a first-in-class intravitreally administered biologic “trap” inhibitor of VEGF-C and VEGF-D currently being investigated in two concurrent phase 3 pivotal trials that will each enroll approximately 990 treatment-naïve patients, in combination with 2 approved anti-VEGF-A treatments, ranibizumab (ShORe trial) and aflibercept (COAST trial).
“Together these financings further validate our strategy to develop OPT-302 as a differentiated therapeutic with the potential to improve patient outcomes in retinal diseases including wet AMD,” said Megan Baldwin, PhD, CEO and managing director of Opthea, in a news release.
Survey Reveals What Patients Think About Health Care Providers
A report that provides insights into what is important to patients with regard to a practice’s website, waiting room, staff, payment process, follow-up communications, and more, revealed that 60% of patients are likely to select one doctor over another if they are able to make appointments online, and 61% place importance on how easy it is to make payments when considering whether to continue seeing a doctor. The report is based on a patient satisfaction survey conducted by the cloud-based digital records company Modmed, in partnership with OnePoll, a market research company. The report is based on 2 random double-opt-in surveys of 1,500 insured and 500 uninsured Americans.
The report found that 73% of patients are likely to keep a “mental scorecard” of all the things they like and dislike about a practice, and that practices are given, on average, 4 chances before a patient decides to find a new provider. “There are countless touchpoints providers have with patients where they can influence a positive experience,” Daniel Cane, CEO of Modmed, said in a news release. “We wanted to provide these insights so providers can stop guessing what’s important to patients and instead be in a position to enhance or create a health-care delivery model that is more in line with today’s connected consumer.”
Multimodal Imaging Reveals Details About Vitelliform Macular Dystrophy
Retinal lesions from vitelliform macular dystrophy (VMD) vary by gene mutation, and addressing these differences may be key in designing effective treatments for this and other rare diseases, according to National Eye Institute (NEI) researchers. Johnny Tam, PhD, head of the NEI Clinical and Translational Imaging Unit, used multimodal imaging to view live cells in the retina — including the light-sensing photoreceptors, retinal pigment epithelial (RPE) cells, and blood vessels — in unprecedented detail, to evaluate the retinas of patients with VMD at the National Institutes of Health Clinical Center.
The researchers evaluated 11 participants using genetic testing and other clinical assessments, and then analyzed their retinas using multimodal imaging. Assessment of photoreceptor and RPE cell density near VMD lesions revealed differences in cell density according to various VDM-associated mutations. IMPG1 and IMPG2 mutations had a greater effect on photoreceptor cell density than RPE cell density. The opposite was true with PRPH2 and BEST1 mutations.
“This study is just one example of how improved imaging can reveal subtle details about pathology in a rare eye disease that can inform the development of therapeutics,” said NEI Director Michael F. Chiang, MD, in a news release.