Advancements in ophthalmology: A comprehensive look at the FDA's 2023 approvals

In ophthalmology, 2023 proved to be a big year, with a staggering 12 approvals by the FDA. On top of those approvals, complete response letters (CRL) were issued to several companies.

When talking about the year and all of its advancements, Peter J. McDonnell, MD, director of the Wilmer Eye Institute and chief medical editor of Ophthalmology Times stated, “I think there has never been a better time to be an ophthalmologist.”

Starting the year off strong, one of the first, and biggest, 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, this marked the first and only FDA-approved treatment for GA.

McDonnell pointed out that it was a major advance to have a therapy for neovascular AMD and now (considering the much larger number of patients with atrophic AMD) this represents an even greater achievement in terms of addressing unmet needs.

“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 payors (especially Medicare) to absorb this additional cost,” McDonnell said.

However, following the approval of pegcetacoplan in February, and after the acquirement of Iveric Bio in July, Astellas Pharma received FDA approval for avacincaptad pegol intravitreal solution (Izervay) in August. The year started with no FDA-approved GA treatments and ended with 2 and countless others in development around the globe.

Apellis wasn’t the only company to come out in 2023 swinging either, as Regeneron had their aflibercept (Eylea) injection approved in February for the treatment of with retinopathy of prematurity (ROP) in preterm infants.

At the time of approval, George D. Yancopoulos, MD, PhD, president and chief scientific officer of Regeneron stated, “until now, the only FDA-approved treatment in common use was laser photocoagulation, a complex and lengthy procedure that permanently ablates retina tissue and is stressful not only for infant patients but also the family navigating a delicate time after a preterm birth.

“For the first time, physicians will now have an FDA-approved medication in EYLEA to treat this heartbreaking disease in these smallest of 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 had 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 the 48-week results of the PULSAR and PHOTON trials – 2 double-masked, active-controlled pivotal trials evaluating Eylea HD compared to Eylea (aflibercept) Injection 2 mg.

Bausch + Lomb announced the FDA approval of perfluorohexyloctane ophthalmic solution (MIEBO) for the treatment of dry eye disease (DED) in May. Which, according to the company, is the first and only FDA-approved treatment for DED that directly targets tear evaporation. It also marked the company’s “first prescription pharmaceutical eye treatment to be approved by the FDA since becoming an independent, publicly traded eye health company,” according to Andrew Stewart, president, Ophthalmic Pharmaceuticals, Bausch + Lomb at the time of approval.

Breaking through with yet another first in the field of ophthalmic drugs was Eyenovia with the FDA approval of MydCombi (tropicamide and phenylephrine hydrochloride ophthalmic spray) 1%/2.5% for inducing mydriasis for diagnostic procedures and in conditions where short-term pupil dilation is desired. This was the first approved, fixed-dose combination of tropicamide and phenylephrine in the US and also the first product using Eyenovia’s proprietary Optejet device to be approved by any regulatory authority.

The first of many CRLs in 2023 was handed down in June to Aldeyra Therapeutics who were seeking the 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 effectiveness” due to “a lack of adequate and well-controlled investigations.” At the time, no clinical trials for ADX-2191 were conducted in patients with PVRL, based on prior discussions with the FDA.

Unfortunately for Aldeyra, this would be 1 of 2 CRLs the FDA would issue to them in 2023.

Most recently in November, the company received a CRL for the New Drug Application (NDA) of reproxalap, for the treatment of DED. This was due to the NDA not demonstrating “efficacy in treating ocular symptoms associated with dry eyes” and that “at least one additional adequate and well-controlled study to demonstrate a positive effect on the treatment of ocular symptoms of dry eye” should be conducted.

The same month Aldeyra was handed a CRL for ADX-2191, Novaliq announced the FDA approval of Vevye (cyclosporine ophthalmic solution) 0.1% for the treatment of the signs and symptoms of dry eye disease. According to Novaliq, VEVYE is the first and only cyclosporine solution indicated for the treatment of signs and symptoms of dry eye disease with efficacy demonstrated after 4 weeks of treatment.

Another first in the field was awarded to Tarsus Pharmaceuticals Inc. when the FDA approved the company’s lotilaner ophthalmic solution 0.25% (Xdemvy) for the treatment of Demodex blepharitis. This became the first and only FDA-approved treatment to directly target  Demodex mites, the root cause of Demodex blepharitis and was approved based on results from 2 randomized, multicenter, double-masked, vehicle-controlled studies (Saturn-1 and Saturn-2).

The second company to receive a CRL was Sun Pharma Advanced Research Company (SPARC) for PDP-716 (brimonidine tartrate 0.35%) for the treatment of patients with Glaucoma, due to inspection findings at a third-party Active Pharmaceutical Ingredient (API) manufacturing facility. The FDA did not raise any issues with the PDP-176 clinical efficacy or safety and no additional clinical data or trials were requested. SPARC had previously licensed global commercialization rights, excluding India and China, of PDP-716 to Visiox Pharmaceuticals Inc.

Outlook Therapeutics was the last company of the year to receive a CRL from the FDA. Lytenava, an investigational ophthalmic formulation of bevacizumab under development 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 further confirmatory clinical evidence.

In September, Ocuphire Pharma and Viatris’ phentolamine ophthalmic solution 0.75% (Ryzumvi) for the reversal of pharmacologically-induced mydriasis (RM) produced by adrenergic agonist or parasympatholytic agents, or a combination thereof was approved by the FDA. Formerly known as Nyxol, the preservative-free, stable eye drop blocks the α1 receptor within 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 to have pilocarpine hydrochloride ophthalmic solution commercially available in the US in the first half of 2024.

A week later, the FDA approved Genentech’s faricimab-svoa (Vabysmo) 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 a single administration per eye of travoprost intracameral implant (iDose TR) 75 mcg, a prostaglandin analog indicated for the reduction of IOP in patients with ocular hypertension (OHT) or open-angle glaucoma (OAG).

On top of all the 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. It’s safe to say 2024 will have to work extra hard to top the year 2023.

Overall, 2023 emerges as a landmark year in the realm of ophthalmology, marked by an extraordinary 12 FDA approvals. The approval of Apellis' pegcetacoplan injection for geographic atrophy marked a significant milestone, addressing an unmet need for GA patients. Even challenges, as evidenced by complete response letters to Aldeyra Therapeutics, solidify the rigorous standards upheld by regulatory bodies. As the year ends, it has set the stage for an exciting future with numerous drugs in the pipeline including APP13007 (clobetasol propionate ophthalmic nanosuspension, 0.05%) from Formosa/Eyenovia, and NVK002 (low dose atropine 0.01%) from Vyluma Inc.

Anticipation for 2024 and beyond in ophthalmological advancements sets a challenge to the forthcoming years to surpass the remarkable strides achieved in 2023.