Eyenovia’s Presbyopia Drop in Phase 3 Study
• Eyenovia, Inc., gave an update in February on the enrollment of its phase 3 VISION-2 trial of MicroLine, its investigational pilocarpine ophthalmic spray for presbyopia. On the heels of a successful Type A meeting with the FDA regarding a refiling of its New Drug Application (NDA) for its combination eye drop of tropicamide and phenylephrine for in-office pupil dilation (MydCombi), Sean Ianchulev, Chief Executive Officer and Chief Medical Officer of Eyenovia, stated in a press release, “Of note, now that our product candidates are classified as combination drug/device products, we will be taking advantage of this requested validation work to streamline development activities for our future programs. One such potential benefit is the potential to reference this device validation work in future regulatory applications, reducing the time and expense of repeating these tests for each program.”
Clearly MicroLine, which uses the same Optejet spray technology as MydCombi, is among the drugs that Eyenovia envisions benefiting from its FDA meeting. “In parallel with these activities, our second Phase 3 VISION-2 clinical trial of MicroLine, our proprietary pilocarpine formulation for the temporary improvement in near vision in people with presbyopia, continues to enroll, and we anticipate reporting results in the second quarter of this year,” Ianchulev said. “We believe the presbyopia market is a nearly $8 billion addressable market in the U.S. alone.”
In the VISION-2 trial, Eyenovia is comparing MicroLine to placebo in 139 patients at sites in 6 states in a randomized crossover trial. The primary outcome measure is the proportion of subjects gaining ≥15 letters in mesopic, high contrast, binocular distance corrected near visual acuity with ≤5-letter loss in mesopic, high contrast, binocular distance visual acuity. Eyenovia expects to complete the study at the end of April.
Glaukos Tests Topical Cream for Presbyopia
• Glaukos Corporation began enrolling in January its phase 2 study of a pilocarpine topical cream to treat presbyopia. The investigational compound, called GLK-302, uses Glaukos’ patented iLution formulation, which allows the drug to be delivered to the eye transdermally through the eyelid following application to the eyelid. Glaukos has already begun testing another iLution compound of pilocarpine, GLK-301, in dry eye disease.
“We believe iLution has the potential to address the major unmet need for presbyopic patients by providing an effective, easy to administer, safe, dropless transdermal therapeutic,” said Thomas Burns, Glaukos’ President and Chief Executive Officer. “The dosing of the first patient in the Phase 2 study brings us one step closer to an innovative near vision solution for the millions of patients who suffer from presbyopia.”
Glaukos’ trial of GLK-302 will eventually enroll 120 patients at 2 locations in Los Angeles and Orange Counties in California. The patients will be randomized to receive 1 of 3 doses of pilocarpine or a placebo. Results from the trial are expected in May 2023.
Ocuphire Announces Phase 2 Nyxol Data
• Ocuphire Pharma, Inc., hosted a virtual investor R&D Day at its Farmington Hills, MI, headquarters on January 31, where data from its phase 2 VEGA-1 study of Nyxol, a low-dose formulation of 0.75% phentolamine, were presented by Jay Pepose, MD, PhD, of the Pepose Vision Institute in St. Louis, MO, and James Katz, MD, from the Midwest Center for Sight in Des Plaines, IL. Drs. Pepose and Katz announced that administration of Nyxol resulted in statistically significant improvement in efficacy and long durability at 12 hours after use compared to placebo. Based on these findings, Ocuphire intends to move forward with phase 3 trials of Nyxol both as a monotherapy and in combination with pilocarpine. The company hopes to file an NDA next year.
“We are excited to host the Investor R&D Day with our prestigious panel of KOLs and share new data from the ongoing APX3330 Phase 2 trial and the completed Nyxol presbyopia Phase 2 trial” said Mina Sooch, MBA, CEO, and Founder of Ocuphire Pharma, in a press release. “We are looking forward to continuing our tremendous progress with these small molecule therapeutic drug candidates with an even more catalyst-rich 2022 as we advance these therapies to patients.”
VEGA-1 enrolled 150 patients who were randomized to receive phentolamine monotherapy, pilocarpine monotherapy, the combination therapy, or placebo. Given the proven efficacy of pilocarpine and the results presented in January, Ocuphire believes it can provide patients with greater flexibility based on patients’ individual needs. The phase 3 trial is set to begin later this year.
Alchemy Vision Project’s New Entry Into Training Curriculum
• In January, Alchemy Systems released a new edition of Entry, its digital curriculum for the training of ophthalmic technicians. The new edition “includes several exciting updates, including a personalized learning roadmap tailored to each technician’s skills and needs, a frequently updated library of lessons, regular live-streamed Deep Dive lessons from industry professionals, quizzes and assignments, a final exam, and an assortment of adaptable study tools to support the training needs of eye care teams across the country,” according to a press release from the company. The new edition also features improvements designed to improve productivity, elevate office culture, and increase staff retention, all while expediting the training process.
Entry, which was introduced in July 2021 and which Alchemy bills as a “First And Only Digital Curriculum Focused Entirely On Ophthalmic Technician Training,” provides self-paced training that most technicians will complete in 6-14 weeks. The course is taught by Certified Ophthalmic Technicians and Certified Ophthalmic Medical Technologists, as well as a number of renowned practicing ophthalmologists. The teaching staff provides lessons, and there are also Deep Dive live streams as part of the overall curriculum. In addition, private practice owners were among the founders of Alchemy, so the company has an inside track on the biggest needs of these practices.
“Today, it is more important than ever to train and invest in your staff to build a strong foundation for growth,” Alchemy’s press release concludes. “It’s time for ophthalmologists to be active participants in the quality training of their technicians to improve the efficiency and success of their practice.”
Short TBUT Associated With More Rapid Presbyopia in Women
• Presbyopia and dry eye disease (DED) are two of the most common conditions in ophthalmology, but the relationships between the two conditions have been unclear. Now, ophthalmologists in Japan have found that progression of presbyopia is worse in women with short tear breakup time (TBUT). Their findings were published online in January by BioMed Research International.
In a clinic-based, retrospective, cross-sectional study, the authors – from Keio University School of Medicine in Tokyo and Otake Clinic Moon View Eye Center in Kangawa -- studied eyes of 1,411 participants with a mean age of 50.1 years old. Upon statistical analysis, they found that, in the subgroup of women with a short TBUT, the endpoint of a near add of 3.00D was reached significantly earlier than in women without short TBUT. They also identified the most severe eye fatigue in participants with near adds of 1.25D to 2.00D.
While the study’s findings are bolstered by the relatively large sample size, they are limited both by the retrospective nature of the study and because it enrolled more than 3 times as many women as men. Prospective studies and even larger samples will be necessary before firmer conclusions can be drawn.
Ayaki M, Negishi K. Short Tear Breakup Time Could Exacerbate the Progression of Presbyopia in Women. Biomed Res Int. 2022;2022:8159669. Published 2022 Jan 28. doi:10.1155/2022/8159669
Largest Study Yet of RLE With Trifocal IOLs
• In one of the largest case series to date, doctors in Scandinavia evaluated the safety and efficacy of a surgical treatment for presbyopia consisting of bilateral refractive lens exchange (RLE) with trifocal intraocular lens (IOL) implantation, finding that the procedure was safe and effective. They reported their findings online in February in the British Journal of Ophthalmology.
The authors, collaborating among 40 centers in Norway, Denmark, and Sweden, conducted a retrospective study of 17,603 cases (35,206 eyes) performed between 2013 and 2019. They analyzed the patient data for multiple outcomes, including uncorrected distance visual acuity (UDVA), uncorrected near visual acuity (UNVA), and IOL power calculation accuracy. The data indicated that, at 3 months after surgery, the mean binocular UDVA was −0.03±0.09 logMAR, with 82.2% of patients with combined binocular UDVA and UNVA equal to or better than 0.00.
Moreover, the authors found that, over time, the outcomes of the procedure improved, with a reduced rate of excimer laser enhancements at the end of the study period compared to the beginning. Finally, at 3 months, the mean manifest refraction spherical equivalent in the patients was 0.00D. The main adverse outcomes were cystoid macular edema and posterior capsular opacification, which occurred in 53 and 35 cases, respectively.
The study marks the publication of the single largest dataset of consecutive patients in whom bilateral RLE was performed with trifocal IOL implantation – a major strength of the study. Conversely, the authors did not include intermediate distance vision among the variables of interest in their study because they do not routinely measure this factor in their practices.
Brenner LF, Nistad K, Schonbeck U. Rethinking presbyopia: results of bilateral refractive lens exchange with trifocal intraocular lenses in 17 603 patients [published online ahead of print, 2022 Feb 2]. Br J Ophthalmol. 2022;bjophthalmol-2021-319732. doi:10.1136/bjophthalmol-2021-319732