NDA submitted to FDA for drug that reverses mydriasis

Ocuphire Pharma has submitted an NDA to the FDA for Nyxol (phentolamine ophthalmic solution) for the reversal of pharmacologically induced mydriasis. The NDA is supported, according to the company’s press release, by positive Phase 3 trials, which included more than 600 pediatric and adult participants. Two Phase 3 trials were conducted in adults, showing statistically significant superiority of Nyxol compared to placebo in returning eyes to baseline pupil diameter. The Phase 3 trial results in pediatric participants, the company reported, “support a potential broader label for Nyxol in [reversal of mydriasis] to include pediatric subjects aged 3 and older.”

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FDA cleared IND application for gene therapy to treat form of Leber congenital amaurosis

Opus Genetics received FDA clearance to begin a Phase 1/2 clinical trial to evaluate OPGx-001, an adeno-associated virus 8 vector to deliver a functional gene, for patients who are affected by vision loss due to mutations in the LCA5 gene, which causes a severe form of Leber congenital amaurosis. According to the company’s press release, the study, which will begin in early 2023, will be an open-label, dose-escalation trial to evaluate subretinal delivery of the functional gene in 9 adult patients. The primary goal is to assess safety and potential benefit. If that is confirmed in adults, the research will move to a pediatric cohort.

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FDA approves IND for research to move forward on RP gene therapy

SparingVision announced that the FDA accepted its IND application for SPVN06, a gene therapy that is being investigated as a treatment for retinitis pigmentosa (RP). According to the company’s press release, this approval allows the company to begin its first-in-human trial with this gene therapy. Safety data will be available in 2023, but the data about primary endpoints will be available in 2025. SPVN06 is described as a “gene therapy approach aimed at stopping or slowing disease progression in patients affected by [inherited retinal diseases] and dry age-related macular degeneration, regardless of their genetic background.”

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Phase 2 study to treat geographic atrophy begins

Linage Cell Therapeutics announced that it and partner Genentech began a Phase 2a, multicenter, open-label, single-arm clinical study for a retinal pigment epithelium cell therapy. According to the company’s press release, the study is evaluating safety and activity with a design to optimize the delivery of RG6501 (OpRegen). The company reported that RG6501 (OpRegen) is being developed under an exclusive collaboration among Linage, Roche, and Genentech.

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Study: Weaning patients off of AMD treatments compared

A study from researchers out of Johns Hopkins University compared the performance of two drugs used for AMD treatment after patients were weaned off the treatment for 1 year. The study, published in the Journal of Clinical Investigation, included 122 eyes (106 patients) with neovascular AMD who had 3 consecutive months of injections with aflibercept (n=70) or bevacizumab (n=52). After this timepoint, there was the potential (based on several metrics) to hold off on further treatment for at least 6 weeks, followed by quarterly monitoring. If needed, treatment was resumed. According to the paper, at 1 year, aflibercept outperformed bevacizumab, with eyes receiving the latter showing similar vision but the need for more injections (on average 8.7 injections compared to 7.2 injections with aflibercept). Eyes that received aflibercept were 3 times more likely to be weaned off treatment completely at this timepoint (43% compared to 15% on bevacizumab). The authors described this as a “previously unappreciated advantage of aflibercept over bevacizumab.” In a press release from Johns Hopkins, researchers said that larger clinical trials might be needed to confirm these results. More research is also needed to better understand why aflibercept is outperforming bevacizumab in this capacity. In addition, the Johns Hopkins press release noted that 56 of the patients were monitored for longer than a year, with 13 of 27 who were treated with aflibercept remaining off treatment at the end of 2 years. Eight of 28 patients treated with bevacizumab remained weaned off treatment at 2 years.

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Possible geographic atrophy treatment explored

Cognition Therapeutics announced that CT1812, which it described as an experimental oral sigma-2 receptor modulator in Phase 2 clinical trials for Alzheimer’s and dementia, could have application as a possible future treatment for geographic atrophy secondary to dry AMD as well. There are currently no approved drugs for dry AMD. In vitro studies were conducted with CT1812 and retinal pigment epithelial cells from induced pluripotent stem cells that were exposed to amyloid beta oligomers and oxidative stress, according to the company. CT1812 was effective at preserving some cellular abilities that would help cells damaged by these elements. The company reported that it began conversations with the FDA to initiate a Phase 2 clinical trial in more than 200 people with geographic atrophy. The paper was published early online November 22 by the Journal of Clinical Investigation. The findings build on evidence from a previous study lead by the Johns Hopkins researchers that found potentially a third of patients with wet AMD could safely pause therapy after one year of monitoring by a physician.

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ASCRS news and events

• ASCRS Annual Meeting: Registration for the ASCRS Annual Meeting, May 5–8, 2023, in San Diego, California, is open now!
• Annual Meeting submission opportunity: Three symposia at the ASCRS Annual Meeting are seeking video case submissions. Find more information here.
• New EyeWorld issue: The December issue of EyeWorld has begun to roll out its articles online and is posted as a flipbook here. Check out the ‘Hot topics in ophthalmology’ covered in this issue.

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Research highlights

• Detection of keratoconus with only analysis of corneal and epithelial thickness maps and OCT was the subject of research that was recently published in the Journal of Cataract & Refractive Surgery. The research, based on retrospective data, looked at the corneal and epithelial thickness maps of normal, manifest, and subclinical keratoconic eyes that were evaluated with SD-OCT. The authors described a “new 2-step decision tree.” “In the first step, if at least 1 of the 4 independent parameters (pachymetry minimum, pachymetry minimum-median, pachymetry superonasal-inferotemporal, and epithelial superonasal-inferotemporal) overruns the cutoff values, the eye was suspicious for KC,” the authors wrote. “In the second step, if the epithelial map showed concentric thinning and the thinnest point of the cornea and epithelium is coincident, the eye was classified as keratoconic.” Using this method, with 172 manifest keratoconic eyes, 21 subclinical keratoconic eyes, and 172 normal eyes, the authors found that step 1 was able to classify 100% manifest and subclinical keratoconic eyes. The researchers found that step 2 was able to rule out eyes that were normal even if they looked suspicious. The authors concluded that these parameters can be used to diagnose keratoconus accurately with a “high level of agreement with the commonly used … Belin-Ambrosio display.”
• A pilot observer-masked, randomized, controlled study in Germany evaluated the use of topical omega-3 polyunsaturated fatty acids for dry eye disease. The research, published in Clinical Ophthalmology, involved 80 patients self-treating with the topical omega-3 (n=37) or povidone eye drops (n=39) for 3 months. Tear breakup time and OSDI scores significantly improved from baseline in both groups, according to the paper. The omega-3 drops were non-inferior to the povidone drops. The authors reported significant improvements in most secondary endpoints “often with a slight difference in favor” of the omega-3 drops (though not statistically significant). The authors concluded with these findings that omega-3 polyunsaturated fatty acids could be an “additional tool for the management of [dry eye disease].”

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