Despite the recent uptick in ophthalmic drug development, there is still significant unmet need in the area of ophthalmology. From 2015 to 2018, an 800% increase was observed in novel ocular drug approvals in the US – however, around 10 million adults still experience a form of vision loss in America, in addition to over 2 billion more worldwide. What’s worse is that, of those, 1 billion have a preventable vision impairment or a treatable impairment that has yet to receive care.
An aging population, rise in digital screen time, and surge in airborne pollution have increased the incidence of eye disease. These factors have positioned the industry for immense growth as it rises to meet the mounting need. We are witnessing much of this growth now, with two ocular drug approvals already in the first half of 2020. Additionally, there are at least nine other ocular products set to achieve major milestones this year - in this post, the Health team at Lubrizol Life Science (LLS Health) reviews these milestones and their implications.
New Drug Approvals in 2020
- Horizon Therapeutics’ Tepezza® (teprotumumab-trbw) injection
In January 2020, Horizon Therapeutics’ Tepezza® (teprotumumab-trbw) injection was approved by the FDA for the treatment of Thyroid Eye Disease (TED). TED can result in vision loss and is associated with several other debilitating symptoms. The Tepezza injection active, a human monoclonal antibody and targeted inhibitor of a specific growth factor receptor, is the first of its kind. It is the only product approved in the US to treat the rare autoimmune disorder of TED. The drug product was granted several designations from the FDA, including orphan drug, priority review, fast track, and breakthrough therapy. Priority review status is a notable trend in ophthalmology, particularly for vascular endothelial growth factor (VEGF) inhibitors. The Beovu® (brolucizumab) injection approved in 2019 is a prime example.
- Allergan’s Durysta™ bimatoprost implant
A few months after the Tepezza injection, the FDA also approved Allergan’s Durysta™ bimatoprost implant. The Durysta implant reduces intraocular pressure in glaucoma patients. It is the only sustained-release, biodegradable product implantable in the eye cavity, known as intracameral, for glaucoma. The first novel glaucoma treatment introduced in over twenty years was commercialized less than three years ago, making the Durysta™ implant particularly noteworthy.
In the past few decades, the ocular market has concentrated primarily on four disease areas:
- Age-related Macular Degeneration (AMD)
- Dry Eye Syndrome
- Diabetic Eye Disease
Figure 1: Top ocular disease states
85% of ophthalmic drug products in development are to treat retinal disorders, dry eye disease, and glaucoma. Nearly 50% are for retinal disorders, primarily diabetic retinopathy and AMD, which is the #1 disease area in development. The second indication with products in development is glaucoma, which encompasses around 20% of ocular pipeline products. Dry eye comprises 15% of ophthalmic pipeline products. Cataracts are an additional area with a significant number of products in development.
In this post, we focus primarily on dry eye disease and retinal disorders, as these are the areas that have made the most progress this year. Products discussed encompass new molecular entities (NMEs) and 505(b)(2) formulations for prescription (Rx) injectables, implants, and topicals (Figure 2). There are additionally several generics in development, most notably biosimilars and Restasis® cyclosporine ophthalmic emulsion generics. Generics are outside the scope of this post, however, if you would like to learn more, our previous post touches upon this topic.
This year has experienced the most growth in NMEs and repurposed APIs, apart from some biosimilars. However, this innovation will likely pave the way for an ocular generics boom in the near future, especially for biologics; Eylea® (aflibercept) injection and Lucentis® (ranibizumab) injection for AMD come off patent this year. As a supplier of high-quality bioadhesive excipients for ocular products, and as a CDMO specializing in sterile products, we look forward to our potential role in this development.
Milestones & Innovations
Dry Eye Syndrome
Treatment options for dry eye syndrome consist of both over-the-counter (OTC) and Rx products. For OTC, eye drops such as Systane® eye drops and Refresh® lubricant eye drops are principal treatment methods and are shorter-term options compared to prescription products. For Rx, Allergan’s Restasis ophthalmic emulsion, launched in 2003, was the first treatment for chronic dry eye.
Novartis’ Xiidra® lifitegrast ophthalmic solution in 2016 and Sun Pharma’s Cequa™ cyclosporine ophthalmic solution in 2019 followed the Restasis emulsion launch. No other approved therapies for chronic dry eye syndrome are currently available in the US Rx market. As a result, many companies are focusing efforts toward the area of dry eye, resulting in substantial innovation. Two late-stage dry eye therapeutics have recently reached significant milestones in their development. The first treatment is a corticosteroid, and the second involves a novel route of administration.
- Kala Pharmaceutical’s Eysuvis™ loteprednol etabonate ophthalmic suspension
In May, Kala Pharmaceuticals resubmitted a new drug application (NDA) for their Eysuvis™ loteprednol etabonate ophthalmic suspension 0.25%, which the FDA has accepted for review. The resubmission for the dry eye treatment came after the FDA’s response to the first submission in mid-2019. Positive Phase 3 clinical trial results support the NDA. The FDA set a Prescription Drug User Fee Act (PDUFA) goal date of October for the completion of its review.
- Oyster Point Pharma’s OC-01 nasal spray
Also in May, Oyster Point Pharma announced encouraging Phase 3 results for its OC-01 nasal spray. The company stated the product demonstrated statistically significant improvement in patients versus control during clinical trials. OC-01 is a selective nicotinic acetylcholine receptor agonist, which is a new drug type for the treatment of dry eye. The nasal spray component of OC-01 also introduces a novel route of administration. This combination of innovation, if approved, could be a significant step for the treatment of dry eye. OC-01 may open doors to other previously unexplored drug classes for treating dry eye.
The retina is a thin layer of tissue lining the back of the eye that converts light into neural signals. The retina then sends these signals to the brain for recognition. The retina is a crucial part of the eye, and as such retinal indications are a leading cause of vision loss. As a result, formulators have focused substantial efforts on back-of-the-eye disorders in the past few years. Blockbuster drugs like the Eylea® injection and Lucentis® injection are key examples. In 2020 at least seven therapies under investigation to treat retinal diseases are due to reach noteworthy milestones.
- Regeneron Pharmaceutical’s Eylea® (aflibercept) injection
Phase 3 clinical trials to evaluate the Eylea injection for dosing intervals of 12 weeks or more will begin later this year. The Eylea injection is approved to treat wet AMD and diabetic retinopathy accompanied by macular edema, but not with the given dosing regimen. Regeneron also recently reported two-year results from their Phase 3 trial evaluating their Eylea injection for the treatment of non-proliferative diabetic retinopathy in patients without macular edema.
- Allergan’s Brimonidine Drug Delivery System® (Brimo DDS)
Allergan stated their Brimo DDS for advanced dry AMD is moving onto Phase 3 trials in 2020. The implant utilizes brimonidine, a selective alpha2 adrenergic receptor drug historically used to lower intraocular pressure in glaucoma patients. The announcement followed positive Phase2A clinical trial results for the 505(b)(2) project. There are currently no approved treatments for dry AMD, despite it comprising over 80% of AMD cases. Brimo DDS could potentially have a considerable impact on AMD patients as a result.
- Opthea’s OPT-302
Opthea completed Phase 2B trials for OPT-302 in 2019 and anticipates topline Phase 2A data later this year. OPT-302 is a fusion protein that functions as a VEGF inhibitor, an increasingly common treatment type for retinal disorders. The company intends to move onto Phase 3.
- Kodiak Sciences’ KSI-301
Earlier this year, Kodiak Sciences revealed that pivotal studies for their anti-VEGF drug KSI-301 would begin in 2020. The product, if approved, will treat diabetic macular edema, non-proliferative diabetic retinopathy, and retinal vein occlusion. KSI-301 is supported by optimistic Phase 1B results.
- Ribomic’s RBM-007
Ribomic’s Phase 2 study to examine RBM-007 for the treatment of wet AMD enrolled its first patients earlier this year. The project is the small Japanese start-up’s most advanced pipeline product; RBM-007 would be their first to market if eventually approved. Ribomic’s start-up status, along with several other organizations listed, is consistent with a common ocular trend. Smaller companies are progressively entering the ocular space and shifting the market away from dominance by the top ten companies.
- REGENXBIO’s RGX-314
REGENXBIO’s RGX-314, another drug in development to treat wet AMD, will soon begin its next trial stage. REGENXBIO previously reported positive Phase 1/2A results. The gene therapy is for suprachoroidal delivery, i.e., in between the layers of the eyeball.
- Roche & Genentech’s Port Delivery System with ranibizumab
Roche and Genentech’s Port Delivery System (PDS) utilizing ranibizumab is undergoing two separate Phase 3 clinical trials. One trial is for wet AMD, and the other is for diabetic macular edema. The implant is surgically implanted and refillable via intravitreal injections.
Figure 2: Common ocular dosage forms and routes of administration
Momentum in the ocular market is building, as evidenced by the significant progress already made in 2020. NMEs and repurposed APIs are being widely explored and utilized, positioning the ocular industry for growth now and in the future. Generics also contribute to the progress made in ocular development – the best example being the impending Restasis emulsion generic and the hype around who will be the first to a market. We will likely see generics contributing more in coming years, however, as current innovation is setting the stage for a generics boom.
With all these factors, the industry and accompanying innovation will doubtlessly continue to develop and grow, signifying crucial progress for patients. This surge in new product development is critical for supporting consumers worldwide, as patient need is at an all-time high. Only time will tell whether the products mentioned will be successful and help reduce the astounding number of people experiencing vision impairment. Regardless, LLS Health is optimistic about the future of ophthalmics and is proud of the role we play in bringing often sight-saving therapies to patients.
LLS Health has a longstanding history of supplying multifunctional ocular excipients; our bioadhesive polymers have been enabling patient-centric ocular products for decades. We also offer medical-grade polymers and CDMO services specializing in sterile and complex products, such as intravitreal injectables. Contact us today to learn more.
Ashley M. Rein | Technical Marketing Specialist