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In ophthalmology, 2023 has proven to be a big year, with an impressive 12 FDA approvals. In addition to these approvals, Complete Response Letters (CRLs) have been issued to several companies.
Speaking about the year and all its advances, Peter J. McDonnell, MD, director of the Wilmer Eye Institute and chief medical editor ofOphthalmology hours said: “I think there has never been a better time to become an ophthalmologist. »
Starting the year strong, one of the first and most important FDA approvals came with Apellis pegcetacoplan injection (Syfovre) for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD). At the time of approval, it was the first and only FDA-approved treatment for GA.
McDonnell emphasized that having a treatment for neovascular AMD was a major breakthrough and that now (given the much larger number of patients with atrophic AMD) it represents an even greater achievement in meeting the needs satisfied.
“The availability of this new therapy will have major implications in terms of the ability of us ophthalmologists to treat this extremely large number of patients and for payers (particularly Medicare) to absorb this additional cost,” McDonnell said.
However, following the approval of pegcetacoplan in February and the acquisition of Iveric Bio in July, Astellas Pharma received FDA approval for avacincaptad pegol intravitreal solution (Izervay) in August. The year began without any FDA-approved GA treatments and ended with 2 and countless other treatments in development around the world.
Apellis wasn’t the only company coming out in 2023 either, as Regeneron had its aflibercept (Eylea) injection is approved in February for the treatment of retinopathy of prematurity (ROP) in premature babies.
At the time of the approval, George D. Yancopoulos, MD, PhD, president and chief scientific officer of Regeneron said: “Until now, the only commonly used treatment approved by the FDA was laser photocoagulation, a complex procedure and long which allows permanent ablation of the retina. tissue and is stressful not only for infants but also for the family going through a delicate period after premature birth.
“For the first time, doctors will now have an FDA-approved drug in EYLEA to treat this heartbreaking disease in these smallest patients,” Yancopoulos added at the time. “We thank the investigators and the many families who participated in the clinical trials. »
Later in the year, Regeneron also aflibercept 8 mg (Eylea HD) approved for the treatment of wet AMD, diabetic macular edema (DME), and diabetic retinopathy (DR). This approval was based on 48-week results from the PULSAR and PHOTON trials – 2 pivotal double-blind, active-controlled trials evaluating Eylea HD compared to Eylea (aflibercept) Injection 2 mg.
Bausch + Lomb announced FDA approval of perfluorohexyloctane ophthalmic solution (MIEBO) for the treatment of dry eye (DED) in May. Which the company says is the first and only FDA-approved treatment for DED that directly targets tear evaporation. It was also the company’s “first prescription pharmaceutical eye treatment to be approved by the FDA since it became an independent, publicly traded eye health company,” according to Andrew Stewart, president of ‘Ophthalmic Pharmaceuticals, Bausch + Lomb at the time of approval.
Another first in the field of ophthalmic medicines was Eyenovia with the FDA Approval of MydCombi (tropicamide and phenylephrine hydrochloride ophthalmic spray) 1%/2.5% to induce mydriasis for diagnostic procedures and in conditions where short-term pupillary dilation is desired. It is the first approved fixed-dose combination of tropicamide and phenylephrine in the United States and also the first product using Eyenovia’s proprietary Optejet device to be approved by a regulatory authority.
The first of many CRLs in 2023 was issued in June to Aldeyra Therapeutics which was seeking approval of ADX-2191 (methotrexate for injection) for the treatment of patients with primary vitreoretinal lymphoma (PVRL) .
The CRL was due to a “lack of substantial evidence of its effectiveness” due to “a lack of adequate and well-controlled investigations.” At the time, no clinical trials of ADX-2191 had been conducted in patients with PVRL, based on previous discussions with the FDA.
Unfortunately for Aldeyra, this would be one of two CRLs the FDA would issue to them in 2023.
More recently in November, the company received a CRL for the new drug application (NDA) of reproxalap, for the treatment of DED. This was because the NDA did not demonstrate “effectiveness in treating ocular symptoms associated with dry eye” and that “at least one additional adequate and well-controlled study to demonstrate a positive effect on treating symptoms ocular symptoms of dry eye” had to be carried out. .
The same month, Aldeyra received a CRL for ADX-2191, Novaliq announced FDA approval of Vevye (cyclosporine ophthalmic solution) 0.1% for the treatment of signs and symptoms of dry eye. According to Novaliq, VEVYE is the first and only cyclosporine solution indicated for the treatment of the signs and symptoms of dry eye with demonstrated effectiveness after 4 weeks of treatment.
Another first in the field was awarded to Tarsus Pharmaceuticals Inc. when the FDA approved the company’s Lotilaner 0.25% ophthalmic solution. (Xdemvy) for the treatment of blepharitis with Demodex. It became the first and only FDA-approved treatment to directly targetDemodexmites, the cause ofDemodexblepharitis and was approved based on the results of 2 randomized, multicenter, double-blind, vehicle-controlled studies (Saturn-1 and Saturn-2).
The second company to receive an LCR was Sun Pharma Advanced Research Company (SPARC) for PDP-716 (brimonidine tartrate 0.35%) for the treatment of glaucoma patients, based on the results of an inspection by a third-party manufacturer of active pharmaceutical ingredients (API). ease. The FDA has not raised any concerns regarding the clinical efficacy or safety of PDP-176 and no additional data or clinical trials have been requested. SPARC previously licensed worldwide marketing rights, excluding India and China, for PDP-716 to Visiox Pharmaceuticals Inc.
Outlook Therapeutics was the latest company of the year to receive a CRL from the FDA. Lytenava, an investigational ophthalmic formulation of bevacizumab being developed as an intravitreal injection for the treatment of wet AMD and other retinal diseases, would have been the first officially labeled ophthalmic formulation of bevacizumab.
The FDA noted several chemistry, manufacturing, and controls (CMC) issues, observations from pre-approval manufacturing inspections, and the need for additional confirmatory clinical evidence.
In September, Ocuphire Pharma and Viatris’ phentolamine ophthalmic solution 0.75% (Ryzumvi) for the reversal of pharmacologically induced mydriasis (MR) produced by adrenergic agonists or parasympatholytic agents, or a combination thereof, has been approved by the FDA. Formerly known as Nyxol, this stable, preservative-free eye drop blocks the α1 receptor in the iris dilator muscle without affecting the ciliary muscle.
A month later, in October, Orasis Pharmaceuticals had its Pilocarpine hydrochloride ophthalmic solution 0.4% (Qlosi) for the treatment of presbyopia in adults approved. Orasis expects pilocarpine hydrochloride ophthalmic solution to be commercially available in the United States in the first half of 2024.
A week later, the FDA approved Faricimab-svoa (Vabysmo) from Genentech for the treatment of macular edema following retinal vein occlusion (RVO). The approval was based on positive results from the global phase III BALATON and COMINO studies and marked the third indication for faricimab-svoa in addition to wet or neovascular AMD and DME.
To end the year on a high note, most recently in December, Glaukos Corp announced the FDA approved its new drug application (NDA) for single administration per eye of intracameral implant of travoprost (iDose TR) 75 mcg, a prostaglandin analogue indicated for the reduction of IOP in patients with ocular hypertension (OHT) or open angle glaucoma (OAG ).
Added to all these approvals are all the drugs in the pipeline for 2024 and beyond. Including APP13007 (clobetasol propionate ophthalmic nanosuspension, 0.05%) from Formosa/Eyenovia and NVK002 (low dose atropine 0.01%) from Vyluma Inc. to name a few. We can safely say that in 2024, we will have to redouble our efforts to surpass the year 2023.
Overall, 2023 appears to be a pivotal year in the field of ophthalmology, marked by an extraordinary 12 FDA approvals. The approval of Apellis’ pegcetacoplan injection for the treatment of geographic atrophy marked an important milestone, addressing an unmet need for patients with GA. Even the challenges, as evidenced by the comprehensive response letters to Aldeyra Therapeutics, solidify the rigorous standards met by regulators. As the year draws to a close, it sets the stage for an exciting future with many drugs in the pipeline, including APP13007 (clobetasol propionate ophthalmic nanosuspension, 0.05%) from Formosa/Eyenovia and NVK002 (low-dose atropine 0.05%) .01%) of Vyluma Inc.
Anticipation for 2024 and beyond advances in ophthalmology poses the challenge for the years to come to surpass the remarkable progress made in 2023.
