- Overview of 2022: A ‘wild ride’
- Insights into the future of AMD
- Discussion focuses on clinically relevant endpoints
- A focus on presbyopia
- The Winning Pitch Challenge
Overview of 2022: A ‘wild ride’
The 2022 Eyecelerator@AAO took place Thursday ahead of the 2022 AAO Annual Meeting with program co-chair Gil Kliman, MD, first sharing a few words about the organization and high-level themes for the meeting.
Eyecelerator is a joint venture between AAO and ASCRS with the goal of helping innovation be more successful and get to the marketplace so it can impact patient care. Dr. Kliman presented on the Eyecelerator hierarchy of innovation, which goes from the invention as the earliest stage through global success at the highest. He said that the field is learning that with innovation we can have positive clinical trials but not successful commercialization. One of the things Dr. Kliman said Eyecelerator wants to help establish is how to identify innovation at earlier stages that has a higher chance of making it to global success so that resources are not wasted on innovations that have a lower chance of being adopted widely by practices.
High-level themes of Eyecelerator@AAO, Dr. Kliman continued, include advancing innovation in uncertain times, new category technologies (both successes and setbacks), and generational transitions taking place in practice and in industry.
Program co-chairs Allen Ho, MD, and Julie Schallhorn, MD, introduced the first session, “A Wild Ride: 2022 in Review.” This session included a presentation by Jeffrey Kimbell on the 2022 political landscape from a regulatory perspective and how it will affect ophthalmic innovation. The session also included a presentation from Kristen Ingenito, with an update on the 2022 ophthalmic market.
Ms. Ingenito said that Market Scope is valuing the 2022 global ophthalmic market at $45.3 billion, with overall growth being higher this year compared to last year. The fastest growing segment is glaucoma surgical, which she said is due to the expansion of drugs and devices in this space, as well as more physicians providing glaucoma procedures. The slowest growing is dry eye pharmaceuticals.
Overall, Ms. Ingenito said there will be about 66.2 million ophthalmic procedures performed this year (including anti-VEGF injections), with dry eye and glaucoma being the fastest growing area for procedures; the slowest growing is cataract.
Ms. Ingenito also shared trend lines showing what happened in the ophthalmic market during previous economic situations, like the 2008 housing market crash and recession, the COVID-19 pandemic, and the market instability since then. There was a big dip in laser vision correction (LVC) during/after the 2008 recession, which Ms. Ingenito said directly impacted the LVC target market. There was an uptick in LVC during the COVID-19 pandemic, but it isn’t back to pre-2008 recession levels. PC-IOLs, on the other hand, continue to grow. Ms. Ingenito said this target audience is less impacted by the market.
Ms. Ingenito also discussed notable U.S. approvals in 2022, IPOs, mergers, etc. She said that while private equity in ophthalmology is down, venture capital is up, with 62% of deals being new ventures.
Looking forward, Ms. Ingenito said there continues to be staffing issues, which affects product adoption, training, and practice efficiency, scope of practice battles with ODs wanting to expand, and the potential for more interest in office-based cataract surgery.
Following these presentations was a panel discussion with Stephen McLeod, MD, and panelists Warren Foust, Euan Thompson, PhD, Andrew Gitkin, Malvina Eydelman, MD, and Wiley Chambers, MD. Dr. McLeod asked Dr. Chambers if the Inflation Reduction Act’s pharmaceutical rules could stifle productivity and reduce output, potentially leading to fewer pharmaceuticals going to the FDA for approval. While Dr. Chambers said he doesn’t have the ability to predict what will happen, he noted that his department has been consistent over the last 4 years with six new drug or biologic approvals each year. The current pipeline is at least double what is typical.
Dr. McLeod asked Dr. Thompson about AI providing new opportunities and its importance in healthcare management. Dr. Thompson said, in general, there is “huge interest” in digital solutions, but it is important to get it right. He said the concept is to create a fully digitally connected workflow solution to drive efficiency, with data flowing seamlessly from one device to the next. Connectivity drives new ways of operating, new ways to connect with patients, new ways to address compliance, and more. AI, he continued, presents a huge opportunity to detect diseases that need treatment earlier and for monitoring disease progression. Overall, there is an immense opportunity for machine learning to help determine what really makes a difference on a patient-by-patient basis and for personalizing healthcare.
Insights into the future of AMD
Allen Ho, MD, Eyecelerator@AAO program co-chair, said that the goal of this session was to bring together the innovators, the things we think are promising, the things that are changing the future, new medicines, new mechanisms, gene therapy, and more. This session featured several companies giving updates on where they’re at with their products in this category.
Cedric Francois, MD, PhD, shared that Apellis Pharmaceuticals is focused on addressing geographic atrophy (GA) by targeting the C3 (complement 3) pathway. In three trials, which have in total enrolled more than 1,500 patients and seen more than 13,000 injections, Dr. Francois said that the efficacy of the drug slowing down progression seems to accelerate over time. An extension study will look at whether these slopes continue to show this pattern, he said.
Dhaval Desai from Iveric Bio discussed avacincaptad pegol for treatment of GA. In its Phase 3 trial, which randomized patients 1:1 to receive either avacincaptad pegol or sham, followed by patients receiving the trial drug going on to be rerandomized for monthly or bimonthly injections and sham continuing monthly injections for an additional 12 months, the primary endpoint was met with a high degree of statistical significance. What’s more, he said the effect of avacincaptad pegol compared to sham was seen early and increased over time. This is the first investigational therapy in GA to achieve its 12-month prespecified primary endpoint in two pivotal Phase 3 studies, Mr. Desai said.
A gene therapy for GA was described by Jill Hopkins, MD, with Gyroscope Therapeutics. She said this company is investigating GT005 to see if complement factor I (CFI) delivered subretinally can modify the balance of the complement system itself. If it can, Dr. Hopkins said that one would expect to see an increase of CFI levels in the vitreous and a reduction of complement pathway factors. Currently, GT005 is being developed as a one-time surgical intervention that would deliver the gene therapy for ongoing expression that would have a continued impact on the complement pathway and reduce GA lesions. In addition to studying the effect of GT005, Dr. Hopkins said Gyroscope is investigating surgical refinements and techniques with the Orbit Subretinal Delivery System, which could potentially better target the therapy and avoid the need for vitrectomy.
Steve Pakola, MD, shared that REGENXBIO is developing an experimental, AAV-based treatment for wet AMD and diabetic retinopathy. RGX-314 is designed to deliver a monoclonal antibody fragment to inhibit VEGF. The company is exploring two potential routes of administration—subretinal and in-office suprachoroidal. The subretinal version has completed its first in-human studies with good durability out to 3 years, he said. Pivotal studies with this version are ongoing. Two studies with the suprachoroidal version are ongoing as well.
While many wet AMD therapies target VEGF-A, Megan Baldwin, PhD, with Opthea shared how OPT-302 is being investigated as complementary anti-VEGF treatment, specifically targeting VEGF-C/D. She said this is the most advanced product in clinical development with demonstrated potential to improve patient visual outcomes. Dr. Baldwin discussed how VEGF-A has some limitations and that the addition of OPT-302 is meant to shut down the remaining pathway and stimulate VEGFR-3 signaling. Phase 2b studies showed more efficacy in a group that received OPT-302 with ranibizumab compared to ranibizumab alone. Phase 3 studies are underway.
Shifting gears from treatments into technologies that can help and/or inform AMD were presentations from Durga Borkar, MD, with Verana Health, who discussed the use of IRIS data and Kester Nahen, PhD, with Notal Vision, who described patient-centric home monitoring services.
Discussion focuses on clinically relevant endpoints
A group ranging from government to industry to academic experts engaged in an interesting discussion on clinically relevant endpoints for approval trials. The session was moderated by Mark Humayun, MD, PhD, and Arsham Sheybani, MD, and included panelists Mark Blumenkranz, MD, from Byers Eye Institute at Stanford University, Wiley Chambers, MD, from the FDA, Terry Dagnon from Outlook Therapeutics, Malvina Eydelman, MD, from the FDA, Peter Kaiser, MD, from the Cleveland Clinic Learner College of Medicine, Omar Sadaruddin, MD, from Santen, and Matt Schlenker, MD, from the University of Toronto.
Dr. Sheybani said the point of the session was to talk about how clinical trials are designed, trial endpoints, the approval process, and what might be meaningful to patients. He started the discussion with the topic of endpoints in glaucoma studies. “A lot of what we deal with are glaucoma surrogates,” Dr. Sheybani said, the most common of which in studies is IOP. He asked whether IOP should be the surrogate in these studies.
Dr. Schlenker said he does think IOP meets most criteria for a surrogate for glaucoma. He said, however, that we need to get away from using mean eye pressures. He thinks we need to look at how many patients are doing well in studies, for example, looking at peak IOPs. That should guide the methodology and statistical analysis, he said. Dr. Sadaruddin said that it is good to not have a one-size-fits-all kind of endpoint and better to customize to the therapy you have. He said he thinks we’re headed in that direction and will have more technology and tests to be able to define and better understand disease progression in the future.
Dr. Chambers clarified that the FDA doesn’t treat IOP as a surrogate for glaucoma, rather it treats it as a particular indication. Later, Dr. Chambers went on to say that most indications are based on what the improvements are going to be for the patient. “Ultimately, we’re going to look at the benefit and compare to risk. If the benefit outweighs the risk, as far as we’re concerned from the clinical side, we’ll go ahead and approve the products.”
Dr. Blumenkranz said the field of ophthalmology is lucky to have great partners at the FDA, like Dr. Chambers and Dr. Eydelman, who “really discuss this in a rational way” and work with us collaboratively to establish these endpoints.
Dr. Kaiser brought up the topic of sustained durability. Reducing treatment burden is not approvable, he said, unless you can show that it leads to better outcomes. At some point we have to figure out how can we use durability and come up with a way that it’s not inferior but also shows to the people we work with that this is something we should do, he said.
A focus on presbyopia
A session moderated by Julie Schallhorn, MD, and Zaina Al-Mohtaseb, MD, highlighted treatments for presbyopia, including lens-based treatments and drops.
The session included Jeannette Bankes with Alcon, Sumit “Sam” Garg, MD, with LensGen, Yari Mitchell with AcuFocus, Erin Powers with BVI Medical, Neda Shamie, MD, with Visus Therapeutics, and Ramin Valian with Allergan.
The discussion first focused on presbyopia drops, particularly Vuity (pilocarpine, Allergan), and Mr. Valian highlighted what’s been learned from the launch of Vuity at the end of last year. This is a potentially large market, he said, and we’re creating a new market that comes with a lot of challenges.
The correct patient selection matters, he said, adding that having a dialogue with eyecare professionals about the right patient selection is very important. Vuity is not for every patient.
It’s also important to set patient expectations. With this drop for presbyopia, many people think it replaces reading glasses, and it doesn’t, he said, though it does reduce their use.
The most critical thing, Mr. Valian said, is with a new innovation, you have to work with physicians to figure out how to incorporate that new technology into practice.
Dr. Shamie stressed that education is incredibly important. More and more patients are coming in empowered with information and wanting spectacle independence, she said. Patients have the ability to learn on their own about the latest innovations, so it’s important for physicians to be able to offer the newest options, or patients will find another physician who does.
Presbyopia drops can help fill a gap, she said. This is an opportunity to capture a patient population for whom we didn’t have good options for, she added.
When looking at education, Dr. Garg said this starts with the patients. They need to understand what to expect, what to look out for, side effects, etc.
He also stressed the importance of doing a comprehensive exam for patients because there were strict entry criteria in the Vuity trial. Though physicians may like to push the limits, there are certain patients that this technology may not be the best option for.
Mr. Valian compared the launch of Vuity and this new market to the launch of Restasis (cyclosporine, Allergan) in the dry eye market. That market did not exist, he said, but over time, it became a large market. “We’re at the beginning [in this marketplace],” he said. “There are so many options that will be available in the future that will make a big difference.” But he added that it’s important to set the expectation that not everything will be a solution for every patient.
In a discussion on presbyopia-correcting IOLs, Dr. Garg said that there is a focus on efficacy when looking at lenses. “I would argue that every premium lens put in a patient is efficacious, but that doesn’t mean that every patient is happy,” he said, adding that the range of vision and quality of vision don’t always match up. “What we need is a lens that gives us both,” he said.
For some patients, Dr. Garg said it takes some time for them to figure out how the lens works for them. “We need a lens that gives range of vision without the side effects of diffractive optics,” he said, adding that there are several options in various stages of development.
Dr. Al-Mohtaseb added that it’s vital for surgeons to have company representatives who know about the technology and know the data. Physicians are relying on some of that data to make decisions about patients, she said.
Dr. Shamie shared some of what she thinks to be the stages of success for presbyopia lenses. First, she said you must pay attention to patient expectations. It’s important to have a menu of options. She also mentioned surgical pearls and postop management. More and more companies should work on helping surgeons with postop management of the unhappy patient, she said.
Ms. Bankes also emphasized the value of postop data for industry. The next generation is big data and AI, she said. As we start to go into a digital ecosystem, we can look at patient selection, diagnostic tools, and see what might work best for what lens and what patient.
Editors’ note: The speakers have financial interests with the companies they represent.
The Winning Pitch Challenge
The Winning Pitch Challenge featured three finalists presenting their pitches to a team of judges. The session was moderated by John Berdahl, MD, and Vance Thompson, MD, with judges Vartan Ghazarossian, PhD, Ranya Habash, MD, Richard Lindstrom, MD, and William Link, PhD.
1st place, $25,000 winner
Vicente Diaz, MD, MBA
Sustained drug delivery
The biggest challenge in treating glaucoma is compliance, Dr. Diaz said. The solution he presented is to mix the drug into a material that dissolves, continuously releasing the medication. The compound can be modified to deliver the medication over days, weeks, or months, then it completely disappears, Dr. Diaz said. This new option would be latanoprost wafers that are made of collagen impregnated with latanoprost.
This is something that matters, he said, because there are 80 million people in the world with glaucoma, and from a financial perspective, there are a lot of resources being devoted to glaucoma.
What is the competition? Drops are what’s available now, and that’s the problem, Dr. Diaz said, adding that Durysta (bimatoprost, Allergan) is another competitor.
Dr. Diaz noted that a manufacturer has been identified to produce the wafers, and a clinical research organization has also been identified to do the trial. They are currently moving forward with plans to speak to the FDA about an IND application
When asked by judges, Dr. Diaz clarified that these would be able to be inserted in the office, either at the slit lamp or the procedure room. It would be possible to put any drug into this product. This will prove the platform and could extend to other uses beyond glaucoma and even beyond ophthalmology, he said.
2nd place, $15,000 winner
Sunil Patel, MD, PhD
Allgenesis Biotherapeutics
Dr. Patel presented products from Allgenesis, a clinical stage, emerging leader with a pipeline of blockbuster biotherapeutics in ophthalmology. The company’s goal is to design novel medicines with a unique mechanism of action to treat unmet medical needs in retinal and ocular surface diseases. The company has two molecules: AG-73305 (for diabetic macular edema) and AG-80308 (for dry eye disease).
AG-73305 is a disease-modifying bifunctional molecule designed to inhibit multiple pathways in retinal disease. It has potent in vitro binding to VEGF and integrin targets. It also decreases vascular leakage and retinal thickness in animal neovascularization models and reduces fibrosis in mouse and monkey fibrosis models. It has shown an excellent ocular safety profile following 2 monthly intravitreal injections to monkeys, he said. Based on compelling preclinical efficacy and safety, a Phase 2a dose escalation study has been initiated in DME patients.
AG-80308 relieves the symptoms of dry eye via resolution pathways, without the negative effects observed with approved immunosuppressive or steroidal treatments. This provides a natural way of resolving inflammation. Dr. Patel said there is currently a Phase 1b dry eye trial ongoing.
In discussion with judges after his presentation, Dr. Patel was advised to focus on one of these products, as it might be hard to fund both projects at once.
3rd place, $5,000 winner
Alejandro Navas, MD, PhD
New Sight Pharma
Dr. Navas shared his long-acting novel liposome formulation containing sirolimus to treat dry eye and immune-mediated eye diseases. Existing treatment options regularly prescribed to minimize the deleterious effects of inflammatory immune-mediated eye diseases have inherent potential toxic side effects. Therefore, an affordable, less irritating option is required in the market. His solution is a novel liposome-containing sirolimus device that is a sustained and stable delivery system. Once applied subconjunctivally, a therapeutic level of sirolimus will be present in the ocular tissues for up to 1 month. He said that these patented liposomes are designed to deliver different types of medications into the ocular tissues after a simple subconjunctival injection avoiding high doses of potentially toxic topical or systemic drugs.
Liposomes containing sirolimus will avoid chronic damage and visual impairment, Dr. Navas said. Initially, a single dose of the liposome suspension containing 60 ug/0.15mL of sirolimus injected subonjunctivally will reduce the inflammation and increase the efficacy of the topical or additional treatment. This would be followed by additional visits. To maintain the chronic protection of the eye and reduce the need for intensive topical or systemic medication, the liposome suspension can be administered periodically, Dr. Navas said.
He spoke about results with this technology and rabbits and mentioned a randomized, triple-blind, Phase 2 clinical trial.
Editors’ note: The moderators and judges have no relevant financial interests. The presenters have financial interests with the companies they represent.
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