Eyes wide open: Biopharma offers new hope across the spectrum of ophthalmic conditions

Introduction

Biopharma innovation has already led to notable advances in the treatment of ophthalmic conditions. In 2017, Luxturna® (Spark Therapeutics, acquired by Roche) became the first gene therapy for an inherited condition to receive FDA approval. Luxturna® uses an adeno-associated virus vector (AAV) to deliver copies of the RPE65 gene to correct mutations found in Leber congenital amaurosis type 2 and severe early-onset retinitis pigmentosa (RP).

More therapies for inherited retinal disorders (IRDs) are advancing. MeiraGTx boasts several clinical stage AAV-vector candidates targeting RPE65-associated retinal dystrophy, achromatopsia - a condition resulting from cone photoreceptor dysfunction - and Leber congenital amaurosis type 4. Its lead asset, a gene therapy for X-linked RP, was acquired by Johnson & Johnson in 2023 for a headline value of $415m. Beacon Therapeutics is evaluating the gene therapy Laru-zova (AGTC-501) in the same condition. EyeDNA Therapeutics (a subsidiary of Coave Therapeutics) is developing HORA-PDE6b to correct PDE6b mutations in inherited retinal dystrophy.

Inherited retinal disorders are thankfully rare. While treatments are highly desirable with respect to their transforming effect on afflicted individuals, the very small eligible patient populations make for a challenging commercial proposition. Despite an $850,000 price tag for treating both eyes, Luxturna® annual revenues have bumped along in the low tens of millions of dollars. Roche recently wrote off Spark Therapeutics for $2.4 billion after acquiring the company for $4.3 billion in 2019.

At the other end of the prevalence spectrum, chronic, disabling ophthalmic conditions such as age-related macular degeneration, diabetic retinopathy, glaucoma and dry eye disease afflict hundreds of millions of people in the developed and emerging economies, with prevalence being driven by aging populations and lifestyle. Unmet needs remain high and offer substantial opportunities for both global biopharmaceutical developers with existing ophthalmology franchises experiencing loss of exclusivity, and for speciality small-cap and private players.

Age-related macular degeneration

Age-related macular degeneration (AMD) afflicts some 100 million people in Europe and the US and is responsible for 4% of all-cause blindness in those aged 50 or over¹. AMD presents in two forms: “dry” AMD and “wet” AMD (also known as neovascular AMD or nAMD), with the wet form characterised by the formation of abnormal, leaky blood vessels in the retina. Anti-angiogenic therapies have transformed nAMD management by slowing disease progression through inhibition of the vascular endothelial growth factor (VEGF) signalling pathway.

Neovascular AMD (“Wet”)

Macugen®, an aptamer VEGF antagonist (Eyetech Pharmaceuticals, acquired by Gilead), was approved in 2004, with a second aptamer VEGF antagonist, Eyelea® (Regeneron and Bayer) approved in 2006. Lucentis® (ranibizumab), a VEGF-specific antibody was approved in 2016, with the bispecific VEGF x angiopoietin-2 antibody Vabysmo® securing approval for nAMD in 2022. Beovu® (Novartis), a VEGF-A specific single chain antibody fragment approved in 2019, has struggled to gain headway, in part due to safety issues.

Eylea's greater efficacy and less frequent dosing requirement helped the drug reach peak revenue of close to $10 billion in 2022 - more than double the peak sales of Lucentis®. The latter being impacted by competition from off-label use of the identical and cheaper cancer treatment, Avastin®. Lucentis® now faces direct competition from biosimilars such as Byooviz® (Samsung Bioepsis and Biogen), with several others on the near horizon from Chong Kun Dang, Xbrane Biopharma, Lupin and Coherus Biosciences. Eyelea® is on the cusp of patent expiry and also faces substantial biosimilar competition.

Next-generation anti-angiogenic approaches include “trap” fusion proteins such as Opthea’s sozinibercept (OPT-302), an inhibitor of both VEGF-C and VEGF-C, and RemeGen’s RC28, a dual inhibitor of VEGF and fibroblast growth factor. Tarcocimab tedromer (Kodiak Sciences) is an anti-VEGF-biopolymer conjugate designed to improve durability of effect. Ocular Therapeutix is hoping to extend time between dosing intervals with Axpaxli®, an intravitreal hydrogel formulation of axitinib, an approved anti-angiogenic small molecule. Duravyu™ (EYP-190: EyePoint Pharmaceuticals) is a slow-release formulation of vorolanib, an investigational small molecule anti-angiogenic.

An attraction of gene therapy is that it offers the advantage of one-time treatment over regular intravitreal injection. ABBV-RGX-314 (Regenxbio and Abbvie), an AAV gene therapy encoding an anti-VEGF antibody is in pivotal studies. Ixo-vec (ixoberogene soroparvovec: Adverum Biotechnologies), an AAV gene therapy encoding aflibercept (the Eyelea® active) is in Phase III evaluation.

Dry AMD

Despite accounting for over 85% of all AMD cases, dry AMD has seen far less therapeutic progress than its neovascular counterpart. The conditions presents a tougher challenge due to its complex pathogenesis involving oxidative stress and retinal inflammation². Early AMD is characterised by accumulation of drusen - rafts of waste protein and lipid – underneath the retina, and by changes in the retinal pigment epithelium (RPE). AMD progression results in RPE death and the loss of light-sensitive photoreceptors, leading to “geographic atrophy” (GA) and severe visual impairment.

Complement inhibition has long been considered to have therapeutic potential in dry AMD³. Despite several late-stage failures, including lampalizumab (Roche), an antibody directed against complement factor D, eculizumab (Alexion, now an AstraZeneca subsidiary), a C5-specific antibody, and tesidolumab (MorphoSys, acquired by Novartis), two complement inhibitors secured FDA approval in 2023: Syfovre®, (pegcetacoplan: Apellis Pharmaceuticals) and Izervay® (avacincaptad pegol: Astellas) Pharmaceuticals), aptamer inhibitors of C3 and C5, respectively. Complement inhibitors in late-stage development include ANX-007 and pozelimab (Regeneron), antibodies specific for complement components C1q and C5, respectively.

Other pharmaceutical strategies which circumvent intravitreal injection are in the works. Gildeuretinol (ALK-001: Alkeus Pharamceuticals), and tinlarebant (LBS-008: Belite Bio), both oral small molecule drugs which act by reducing retinal accumulation of toxic vitamin A dimers are in Phase III development. BI 1584862 (Boehringer Ingelheim), an orally available phospholipid modulator, and zervimesine (CT1812: Cognition Therapeutics), an oral small molecule sigma-2 receptor antagonist which restores the waste elimination function of retinal pigment epithelial cells, are both in Phase II evaluation. Elamipretide (Stealth Biotherapeutics) is a subcutaneously delivered peptide which binds cardiolipin, thereby improving mitochondrial function.

Gene and stem cell therapies under evaluation in dry AMD include OCU410 (Ocugen), which uses an AAV vector to deliver the RAR-related Orphan Receptor A gene, the corresponding protein playing a central function in lipid metabolism. JNJ-81201887 (previously HMR59: Johnson & Johnson) aims to boost soluble CD50 expression to inhibit membrane attack complex formation and thereby preserve RPE function.

Optogenetic approaches do not seek to correct underlying genetic defects but work by introducing light-sensitive proteins into surviving retinal cells, enabling them to act as photoreceptors. GS030 (GenSight Biologics) introduces a gene encoding a light-sensitive protein into retinal ganglion cells and stimulates them with intense light of a selected wavelength delivered by goggles.

Lineage Therapeutics, in collaboration with Roche, is evaluating OpRegen®, while Astellas is developing ASP7317, both being suspensions of human allogenic RPE cells administered underneath the retina.

Diabetic retinopathy and diabetic macula edema

Diabetes greatly raises the risk of macrovascular and microvascular complications. Among these being diabetic retinopathy (DR), a condition estimated to afflict around a quarter of all diabetics to some degree - equating to over 100m people globally - and set to rise with projected increases in diabetes prevalence⁴. Early DR presents as retinal microaneurysms, which, if not contained through tight blood sugar control, progress to blood vessel damage, fluid accumulation and vision loss. Diabetic macular edema (DME), the accumulation of fluid in the centre of the retina (the macula), is a complication of DR, resulting in loss of central vision.

Like nAMD, DME benefits from anti-angiogenic therapies such as Lucentis®, Eyelea® and Vabysmo®. A number of investigational therapies targeting nAMD are also under evaluation in DME and/or non-progressive DR, including tarcocimab tedromer (Kodiak Sciences), RemeGen’s RC28, and EyePoint’s vorolanib-delivering hydrogel (EYP-190).

Non-angiogenic approaches in clinical development include foselutoclax (UBX1325: Unity Biosciences), a senolytic Bcl-xL inhibitor; vamikibart (R07200220: Roche), an anti-IL-6 antibody under evaluation in DME patients in combination with Lucentis®; PER-001 (Perfuse Therapeutics) a first-in-class small molecule endothelin receptor antagonist delivered via an intravitreal implant; tonabersat (Inflammx Therapeutics), an oral connexin43 inhibitor (repositioned after failure in several CNS indications), and runcaciguat (Bayer) an oral neuroprotective soluble guanylate cyclase activator. Restoret™ (Merck, acquired with EyeBio) is an intravitreal tri-specific antibody fragment Wnt agonist.

Glaucoma

“Glaucoma” is a catch-all term for a group of progressive optic neuropathies characterised by increased ocular pressure, degeneration of retinal ganglion cells and nerve fiber layers, and changes in the optic nerve head. The global prevalence of glaucoma is estimated at some 80m afflicted individuals, although only half are symptomatic at diagnosis.

The objective of pharmacological management is to reduce intraocular pressure and increase drainage, most commonly achieved through topical beta-blockers such as timolol, or prostaglandin analogues including latanoprost, travoprost and bimatoprost. Current innovation is focused on novel analogues and delivery systems. Novel agents in Phase III development include NCX 470 (Nicox Ophthalmics), a dual-action, nitric oxide-donating bimatoprost formulation, and sepetaprost (DE-126: Santen Pharmaceuticals), a prostaglandin analogue which acts upon both FP and EP3 receptors to give more effective pressure reduction. Dazdotuftide (Tarsier Pharma) is a novel topical anti-inflammatory, acting through both the Nf-kB signalling pathway and the shifting of pro-inflammatory (M1) macrophages to a non-inflammatory M2 state.

Potentially more effective or convenient prostaglandin analogue delivery systems in clinical development include POLAT-001 (Lipolat: Peregrine Ophthalmic), a nanoliposome formulation providing sustained released of latanoprost, and Paxtrava (OTX-TIC, Ocular Therapeutix), travoprost-loaded microparticles held in an implanted bioresorbable hydrogel. Other investigational sustained release implants include PA5108 (PolyActiva) and ENV515 (Envisia Therapeutics), delivering latanoprost and travoprost, respectively. LL-BMT1 (MediPrint Ophthalmics) is a proprietary bimatoprost -eluting soft contact lens.

Dry eye disease

“Dry eye” is a complex condition with two broad subtypes: “aqueous deficient” and “evaporative loss” dry eye. These result from insufficient tear film production or accelerated loss, respectively, with both subtypes causing inflammation and discomfort⁵. An estimated 10-20% of individuals over 40 years suffer from dry eye, with autoimmune conditions, diabetes and certain medications being contributory factors.

Effective pharmacological management is complicated by the multifactorial nature of chronic dry eye disease. Several approved topical preparations contain varying concentrations of the anti-inflammatory drug, cyclosporine. Other approved anti-inflammatories include lifitegrast (Xiidra®: Novartis) which acts through ICAM-1 blockade to downregulate T cell-mediated inflammation, and the corticosteroid loteprednol (Eysuvis ®: by Kala Pharmaceuticals). Varenicline, a once-widely prescribed smoking cessation drug, is effective in stimulating tear production when delivered by nasal spray (Tyrvaya®: Oyster Point).

Non-steroidal anti-inflammatories in clinical development include reproxalap (Aldeyra Therapeutics), for which FDA approval hangs on submission of additional efficacy data, and IC 265 (Iacta Pharma), a SYK kinase inhibitor. Licaminlimab (OCS-02: Oculis) is a topical formulation of an anti-TNFα antibody fragment. ST-100 (vezocolmitide: Stuart Therapeutics) is a topical formulation of vezocolmitide, a collagen peptidomimetic which may promote collagen repair.

The meibomian glands are responsible for the production of lubricating oils in the eye. AZR-MD-001 (Azura Ophthalmics) is a selenium sulphide-containing ointment capable of preventing keratin buildup which impairs meibomian gland function. Acoltremon (Alcon) is a first-in-class topical agonist of transient receptor potential melastatin 8 (TRPM8), a protein present in the cornea and eyelids, and induces a cooling sensation which mimics that of natural tear drying to induce tear production. In May 2025 the FDA approved Acoltremon and it will be branded as Tryptyr.

The future looks bright

Over the past two decades, biopharmaceutical innovation has expanded treatment options across the spectrum of ophthalmological conditions - from ultra-rare IRDs to common chronic conditions affecting hundreds of millions of people globally. Prevalence is expected to rise with aging populations, increasing rates of diabetes, and widespread digital screen use. A 2020 estimate places the loss to the global economy from sight loss and visual impairment at over $400 billon, with 90% of cases being preventable or treatable ⁶.

While the value proposition for IRD gene therapies is challenging, historical revenues for nAMD treatments such as Lucentis® and Eyelea® rival or exceed those of leading precision cancer treatments. Loss of exclusivity has spurred both innovation and me-too development in nAMD, driving the emergence of more effective and conveniently dosed treatments. At the same time, cheaper biosimilar are expanding the market by enabling access for a broader patient population. The dry AMD market, which represents more than 85% of AMD sufferers, is only just opening up and offers enormous scope - particularly for the next generation of treatments that aim to deliver meaningful and sustained improvement in visual acuity, rather than merely slowing the progression of geographic atrophy.

Novel anti-angiogenic and non-angiogenic therapies can be expected to bring more diabetic retinopathy sufferers under treatment. In parallel, proprietary drug delivery platforms and novel agents targeting previously unexploited inflammatory pathways and ocular homeostasis mechanisms will expand the already lucrative markets of glaucoma and dry eye disease management. Together, these advances mark the beginning of a new era in ophthalmic innovation – one that offers broader reach, improved outcomes and sustained commercial opportunity.

 
Table 1. Late-Stage Ophthalmology Pipeline

Candidate	Category	Mechanism or Drug Class	Phase
Neovascular (“wet”) age-related macular degeneratiom
ABBV-RGX-314 (AbbVie, Regenxbio)	Gene therapy	Gene construct encoding anti-VEGF antibody fragment	Phase III
Tarcocimab (Kodiak)	Antibody-biopolymer conjugate	Anti-VEGF antibody (sustained release)	Phase III
Apaxli™ (Ocular Therapeutix)	Intravitreal hydrogel	Sustained release of axitinib (anti- angiogenic)	Phase III
RC28 (RemeGen)	Recombinant fusion protein	VEGF and fibroblast growth factor inhibitor	Phase II/III
“Dry” age-related macular degeneration
ALK-001 (Alkeus Pharmaceuticals)	Oral small molecule	Retinol binding protein 4 antagonist	Phase III
Elampretide (Stealth Biotherapeutics)	Peptide	Cardiolipin binder	Phase III
Tinlarebant (Belite Bio)	Oral small molecule	Retinol binding protein 4 antagonist	Phase III
BI 1584862 (Boehringer Ingelheim)	Oral small molecule	Phospholipid modulator	Phase II
Diabetic retinopathy/diabetic macular edema
Vamikibart (Roche)	Biologic	Anti-IL-6 antibody in combination with anti-VEGF treatment	Phase III
Foselutoclax (Unity Biosciences)	Small molecule	Senolytic Bcl-xL inhibitor	Phase II
PER-001 (Perfuse Therapeutics)	Small molecule	First-in-class endothelin receptor antagonist (intravitreal implant)	Phase II
Runcaciguat (Bayer)	Oral small molecule	Neuroprotective soluble guanylate cyclase activator	Phase II
Glaucoma
NCX 470 (Nicox Ophthalmics)	Small molecule	Nitric oxide-donating bimatoprost formulation	Phase III
Sepetaprost (Santen Pharmaceuticals)	Small molecule	FP and EP3 receptor agonist	Phase III
Dazdotuftide (Tarsier Pharma)	Small molecule	Dual-action anti-inflammatory (Nf-kB pathway and M1 macrophages)	Phase II
QLS‑111 (Qlaris Bio)	Small molecule	ATP-sensitive potassium channel modulator	Phase II
Dry eye disease
Vezocolmitide (Stuart Therapeutics)	Peptidomimetic	Promotion of collagen repair	Phase III (Completed)
IC 265 (Iacta Pharma	Small molecule	SYK kinase inhibitor	Phase II
Licaminlimab (Oculis)	Biologic	Anti-TNFα antibody fragment, topical delivery	Phase II
Acoltremon (Alcon)	Small molecule	Agonist of transient receptor potential melastatin 8 (keratolytic)	Submitted for marketing approval (US)

References

1. Vision Loss Expert Group of the Global Burden of Disease Study. Eye 38, 2070–2082 (2024).

2. Vyawahare H & Shinde P. Age-Related Macular Degeneration: Epidemiology, Pathophysiology, Diagnosis, and Treatment. Cureus. 2022 Sep 26;14(9): e29583.

3. Desai D & Dugel PU. Complement cascade inhibition in geographic atrophy: a review. Eye 36, 294–302 (2022).

4. Wong TY & Tan TE. The Diabetic Retinopathy "Pandemic" and Evolving Global Strategies: The 2023 Friedenwald Lecture. Invest Ophthalmol Vis Sci. 2023 Dec 1;64(15):47.

5. Lifei Yu et al. Recent Developments About the Pathogenesis of Dry Eye Disease: Based on Immune Inflammatory Mechanisms. Frontiers in Pharmacology. Volume 12 – 2021. DOI=10.3389/fphar.2021.732887

6. The Vision Atlas (The International Agency for the Prevention of Blindness). https://visionatlas.iapb.org Accessed May 2025.


With sincere thanks to Onyeka Awunor (Consultant Intern) for her thorough and valuable desk research.

 

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