Held on 15th October 2020, the OIS Glaucoma Innovation Showcase 2020 presented both drugs and devices under development for the treatment of the second leading cause of blindness globally — glaucoma. Attendees gained valuable perspectives from clinical and industry leaders. Here are some of the highlights…
Introducing the Rockstars of Glaucoma Therapy
“Six years ago, we were focused on raising money to move Rhopressa into phase 3 and Rocklatan into phase 2. Looking back at all our past, it gives us a great feeling to see how far we’ve come and how much we’ve accomplished,” said Dr. Tom Mitro, president and chief operating officer of Aerie Pharmaceuticals, opening the session with a narrative of the company’s journey.
How has the company weathered the storm to be where it is today? According to Dr. Mitro, Aerie Pharmaceuticals (North Carolina, USA) continues to pick up speed as it strives to be the leading company in glaucoma therapy worldwide. “We’ve recently released the result of a 260-patient, phase 4 study done in the United States that demonstrated that Rhopressa consistently lowered IOP by >4 mmHg, regardless of whether added to prostaglandin monotherapy as the first, second, third or fourth adjunctive agent,” he shared.
Clinicians have attested to the “rockstar” status of these products. “Ophthalmologists tell us that these are excellent results that mirror their actual clinical experience with the use of Rhopressa,” said. Dr. Mitro.
“We believe that Rhopressa’ s results are due to its unique mechanisms of action different from today’s available adjunctive agents,” he added. Additionally and more importantly, Rocklatan (netarsudil/latanoprost ophthalmic solution) is the only product that demonstrates statistical superiority over latanoprost, which is the top selling product in the United States, in robust, phase 3 trials.
Dr. Mitro explained the performance of Rocklatan and Rhopressa (netarsudil ophthalmic solution) during the pandemic. “Our franchise units sold in the pharmacies have increased regardless of the pandemic. In September, 90,000 units of Rhopressa and Rocklatan were sold in the pharmacies, an increase of 21% versus April, bringing our annual sales to almost 1 million units,” he shared.
The news is great on the other side of the pond as well. “In Europe, the second biggest glaucoma market in the world, Rhokiinsa (the European name for Rhopressa), was approved a year ago, while Rocklanda (the European name for Rocklatan), will hopefully be approved in Q1 2021, making both products available for marketing in the EU,” said Dr. Mitro. Aerie Pharmaceuticals recently announced the 3-month top line results of Mercury 3 study, which showed Rocklanda achieved non-inferiority to Ganfort (a high priced, top selling combination in Europe). Rocklanda has a safety advantage, which, unlike Ganfort, does not contain a beta blocker, highlighted Dr. Mitro.
Additionally, Aerie’s manufacturing plant in Ireland, which the company built from the ground up, is FDA approved to produce both products.
And it gets better, noted Dr. Mitro. “Japan is the third largest glaucoma market in the world and we successfully completed a phase 2 study, which produced postive results that convinced the PMDA (Pharmaceuticals and Medical Devices Agency; Japan’s FDA equivalent) to allow us to commence phase 3 trials before the end of 2020. We’re excited about the market opportunities in Japan because the IOP levels are much lower than here and Rhopressa works very well at low pressures,” shared Dr. Mitro.
A Brave New World in 24/7 IOP Monitoring
“As you all know, elevated IOP (intraocular pressure) is the primary and only modifiable risk factor for glaucoma and all treatments aim to reduce it,” said Smartlens CEO, Dr. Savas Komban. Describing the current treatment gaps, Dr. Komban emphasized that there are many studies which have shown a correlation between our limited understanding of IOP and the treatment challenges physicians face in managing glaucoma. “The need has long been defined by doctors and key opinion leaders,” Dr. Komban said.
Sharing his underlying motivation, Dr. Komban said: “I have a personal connection to glaucoma as my parents are sufferers of the condition, so I am also at a high risk. As a company we are addressing this significant need with a novel approach.”
According to Dr. Komban, “We started at Stanford University, and spent five years developing and conducting preclinical trials. The results of years of work is the miLens®, a soft contact lens with an embedded microfluidics pressure sensor.”
“Clinical trial data have been excellent thus far, all measurements between 1 mmHg accuracy compared with Goldman. Physiological factors such as tear film thickness and blinking did not affect our measurements,” he shared.
Furthermore, Dr. Komban emphasized the product’s unique features: miLens® has a clear competitive advantage by being an easy-to-use, non-invasive and electronics-free device, which provides accurate results and does not need additional training or hardware. “It can be used for screening, it’s affordable and accessible to anyone who needs it,” he said.
Talking about existing IOP monitoring devices in the market, Dr. Komban stated that these are far from being an ideal solution. “They are expensive, complicated and do not provide accurate results,” said Dr. Komban. “Around 5mmHg in the best case, which is not clinically acceptable. Also, they also have other requirements such as surgery, long training and need for additional hardware,” he added.
How exactly does miLens® work? “When prescribed by the doctor, miLens® users are notified to take pictures throughout the day either by wearing our goggles or by using their smartphones. Those pictures are uploaded into the cloud server, processed with our software which calculates the IOP results. Results are displayed on an easy-to-use dashboard,” explained Dr. Komban.
“We have developed three product packages that are fully customizable and reimbursable. Our clinical studies will be completed next year, our regulatory pathway is 510K and we anticipate FDA clearance in two years,” he concluded.
For the Toughest Glaucomas, that Eureka Moment has Arrived!
For the over 1.6 million people in the United States who have normal tension or severe glaucomas (NTG), current treatments just don’t work, emphasized Dr. John Berdahl, founder and chief medical officer of Equinox (California, USA).
“And it appears we now have a solution at hand,” said Dr. Berdahl. Equinox, according to Dr. Berdahl, is pioneering a new understanding of glaucoma based on deep exploration into the physics of the eye and eye pressure. “This new understanding is based on the discovery and research into Multi-Pressure Glaucoma Management, or MGM,” he shared.
The device, Mercury Multi-Pressure Dial is the first non-surgical, non-pharmacological, connected care option for glaucoma.
How exactly does this revolutionary technology work? “Our bodies are constantly under atmospheric pressure. MGM utilizes the natural laws of physics to balance pressures in and around your eye. Using the goggles, a mild negative pressure is applied in the front of the eye, the pressure inside the eye is reduced while maintaining the pressure everywhere else on the body, and the balance of pressures inside and behind the eye is delicately restored,” explained Dr. Berdahl.
Further, Dr. Berdahl highlighted available data to support the efficacy of MGM. He said the published data has been impressive. “We are able to titratably dial in eye pressure to exactly what we want the target IOP to be. We have studied this in over 500 eyes and are currently waiting for FDA approval,” he shared.
“This device lowers IOP predictably and precisely. It is safe, with an extremely low risk of complications and it treats patients overnight when their eye pressure is elevated and their blood pressure is reduced, and the optic nerve is most vulnerable to damage,” Dr. Berdahl concluded.
Toxic Molecules in the Retina: It is Time to Go!
Toxic molecules in the retina, known as Aβ oligomers, are long recognized as the bad guys that glaucoma and dry age related macular degeneration (AMD), may have finally met their match. “At Galimedix, we are fighting the major causes of blindness and neurodegeneration,” said Executive Chairman Dr. Alexander Gebauer of Galimedix Therapeutics (Maryland, USA).
“Our technology is a small molecular platform with a novel mode of action, and we have potential in neuroprotection and direct functional improvement,” said Dr. Gebauer. Current target indications for this molecule are glaucoma, dry AMD and Alzheimer’s. Moreover, compelling efficacy has been shown in in vitro and in vivo studies, and in phase 1 trials completed in both healthy subjects and glaucoma patients.
Explaining the goal of the company, Dr. Gebauer stated that Galimedix’s primary focus is to improve and maintain vision for patients in need. Studies have shown that blindness and cancer are the most feared health conditions, and glaucoma and dry AMD are the two leading causes of blindness. “Both diseases are associated with aging populations and are due to neurodegeneration of the retina,” he noted.
“GAL 101 can prevent the formation of, and eliminate existing toxic oligomers from the retina and the brain. We have shown that we can restore lost function in preclinical models. Our phase 1 is complete with excellent safety data, and no treatment related adverse events were recorded,” shared Dr. Gebauer.
On the next phase for product development, Dr. Gebauer said that the company has designed clinical studies with top notch global leaders in glaucoma and dry AMD. “These are functional improvement studies, which will increase the probability of success in phase 2 studies. GAL 101 is our lead compound, but we have other compounds in the pipeline,” Dr. Gebauer added.
MINIject®: A New Definition of the MIGS Class
iSTAR is a company that focuses on the micro-invasive glaucoma surgery (MIGS) segment, which is the fastest growing segment in ophthalmic devices. CEO of iSTAR (New York, USA) Michel Vanbrabant, shed light on the company’s innovative leading IOP lowering implant called MINIject®.
“MINIject® is made of antifibrotic medical grade silicone, which is very different from existing MIGS technologies. It has demonstrated best-in-class performance in clinical trials,” shared Mr. Vanbrabant.
The device comes as a preloaded injector while the implant is 5 mm long, extremely soft and conforms to the eye anatomy. Inside, it is 100% made of a matrix of interconnected pores, unlike other devices made of a single lumen. A green ring helps the surgeon implant to the correct depth, which is vital toward preventing endothelial cell loss on the cornea.
Sharing topline results of a preclinical study recently published in the journal BMC Biomedical Engineering, Mr. Vanbrabant said: “We show that following implantation, pore colonization is activated and continues up to 6 months post implantation in rabbits. Stability is reached at 6 months with no further cell migration.”
Data from clinical studies, STAR-I and STAR-II have been published in high impact journals and these demonstrate the clinical utility of MINIject®.
According to Mr. Vanbrabant, when patients were followed-up in the STAR I study, investigators have seen stability of IOP up to 24 months, with an average of 13.8 mmHg, representing a 41% reduction compared to baseline. “Of note, about half of the patients were medication -free at 24 months,” he shared.
“On safety of the implant, one of the most important safety data we observed is that only 5% of patients had to undergo secondary surgery. Also we found hypotony in only 1.3% and IOP spikes in 5.1% of patients,” said Mr. Vanbrabant.
According to the study’s investigators, the data available so far suggest that MINIject® works effectively, may help prevent risks and improves patient management compared with other surgical implants. “The implant adapts well to anterior segment anatomy and scleral curvature, so there is no contact with corneal endothelium,” said Mr. Vanbrabant. iSTAR plans to obtain a CE mark at the end of this year and FDA clearance in 2025.
MIMS: A New Gold Standard for Surgical IOP Treatment
Sanoculis rose to this great challenge by developing MIMS (minimally invasive micro sclerotomy. According to Mr. Nir Israeli the CEO of Sanoculis, MIMS is a simple, fast, and stent-less procedure which creates a sclero-corneal drainage channel to reduce IOP in glaucoma patients, and with efficacy similar to gold standard trabeculectomy.
“The system is composed of a foot switch, controller and a disposable handpiece unit,” said Mr. Israeli.
The procedure is very simple. “The surgeon creates a side pore, injects viscoat and introduces the device into the angle of the eye. Once in position, the surgeon presses a footswitch and the drill goes out and backwards automatically, taking a cylinder of tissue to create the sclerotomy which drains aqueous from the anterior chamber to the subconjunctival space,” explained Mr. Israeli.
How does MIMS perform in the hands of surgeons? To address this question, Mr. Israeli shared some recently published data. “MIMS has a superior safety profile due to its minimal invasiveness and the fact that no tissue is left behind. Thus far, we have operated on 151 patients with impressive results. In a 12-month follow-up we found IOP reduction of 50% and a 58% reduction in medications. The average duration of the procedure was 2 minutes with no major intra- and postoperative complications. Imaging of drainage channels show excellent results on drainage patency at 1 year postoperative evaluation,” he shared.
“Having operated on a dozen patients with the MIMS device and procedure, I can state that the device requires a short learning curve, it is safe and provides an alternative to the stent procedures,” added Prof. Ike Ahmed.
“The fact that nothing is left behind keeps future therapeutic options open, which is a major advantage,” Mr. Israeli said.
Sanoculis intends to file for FDA registration via the 501k De-Novo route. This requires a clinical validation study which will compare their product with trabeculectomy with a follow-up period of 1 year.
Sustained IOP Control in Glaucoma? Just CTRL+P
Today, ocular drug delivery has remained antiquated and inadequate, according to Dr. Dan Myers, the CEO of Leo Lens. “This 20th century approach that relies on eye drops means we continue to worry about noncompliance, low bioavailability and side effects of chronic exposure to preservatives,” he said.
Leo Lens (California, USA) has successfully harnessed the power of digital printing, with its patented MediPrint® process, to use contact lenses as a continuous drug delivery system. According to Dr. Myers, the company believes that the future approach should be with continuous non-invasive dosing with [our] patented Mediprint® technology.
“We can provide 24/7 continuous delivery of medication in a weekly therapy by printing the drug onto a weekly contact lens, and the drug is printed in the periphery of the contact lens, away from the optical part,” said Dr. Myers,
“In addition to glaucoma, we can print multiple compounds already approved by the FDA for dry eye, allergy, infection and myopia,” he added.
The market potential is excellent, according to Dr. Myers. “We are seeing a paradigm shift with more and more optometrists performing early eye exams and detecting mild to moderate stages. We hope this could be a strong incentive for optometrists to use lens-based treatments, but ultimately, the patients are the greatest beneficiaries because they will enjoy continuous medications without the need for daily eye drops,” he explained.
Additionally, Dr. Myers provided market size estimates and noted that about 37% of glaucoma patients are between 40 to 64-years-old and most have mild to moderate disease. “We have seen that 50 to 60% are willing to accept contact lens-based treatment, and assuming 1 in 5 of these patients are treated with Mediprint, this represents a 360 million-dollar revenue opportunity,” he shared.
Protecting the Ocular surface: There is no going BAK
TearClear (Massachusetts, USA) is disrupting the way topical medications are delivered to the ocular surface. “Our vision is to ensure efficacy without compromising safety of the ocular surface,” said company CEO Dr. Robert Dempsey.
As we all know, preservatives like benzalkonium chloride (BAK) in ocular medications may cause ocular surface damage and approximately 70% of ophthalmic drugs contain BAK, Dr. Dempsey highlighted.
On the uniqueness of the company’s novel platform in today’s eyedrop market, Dr. Dempsey stated emphatically that “TearClear offers the only pharmaceutical platform where BAK preserved drugs are delivered as preservative-free doses.”
Given that up to 30% of patients will experience moderate to severe ocular surface disease following chronic BAK exposure, Dr. Dempsey explained that “TearClear is addressing an unmet medical need, targeting glaucoma drugs in a USD 4 billion market, and are strategically priced for profitable reimbursement.”
This technology can be used for many topical ophthalmic medications. “Our platform is versatile and can be applied in over 10 ophthalmic products in which we have successfully demonstrated preservative-free delivery of active products post-administration,” explained Dr. Dempsey.
“We have demonstrated efficacy and safety via a pilot clinical trial, and we have confirmed our regulatory path with the FDA via the 505(b)(2) route,” he added.
Glaucoma Therapies and Development: Current and Future Perspectives
In the panel discussion portion of the session, moderated by Dr. Ehsan Sadri, glaucoma clinical experts shared their thoughts on the most exciting innovations on the field and future directions in innovation.
“We need devices that are safe, efficacious, easy to administer by all physicians treating glaucoma patients,” said Dr. Janet Serle. Both meds and devices will continue to be needed, she noted. “And now there’s new evidence that laser surgery can be helpful in early stages of glaucoma,” added Dr. Serle. She also emphasized that she would like to see next in the market is multiple medications in one device, a direction that some companies hope to go.
On the other hand. Prof. Ike Ahmed is looking into a five-year horizon. “I’m excited about what we could possibly do with gene therapy,” he said. “We are already seeing this in the retina, the ability to alter receptors and change gene expression,” he noted.
This holds tremendous promise for pressure lowering, as well as neural pathology. “I’m also excited about diagnostics, the ability to pick up diseases earlier and about using big data and AI. And soon, maybe we will be able to detect risks for glaucoma using cellphones. I also look forward to seeing more nontypical approaches to pressure lowering like electroceuticals, multi-pressure dial and novel drug delivery,” Prof. Ahmed added further.
Moving on to the topic of impactful tools in the clinic today compared to 10 years ago, Dr. Paul Singh said that diagnostics have allowed us to appreciate progression today more than we ever had before. “For example, the new MIGS procedures allow us to intervene much earlier. Diagnosis of apoptotic retinal cells (DARC) technique is something exciting for me, and which allows us to diagnose retinal cell damage way earlier than before as they become apoptotic. However, we know that in a subset of patients with MIGS devices, we can’t stop disease progression, so these are the patients that give me concern,” he explained.
On the Future of Glaucoma and Glaucoma Business Development
Last but not least, Dr. Robert Rothman led the discussions with industry experts on the impact of COVID-19 on glaucoma practice and how the pandemic has caused a change in business focus (if any).
Mark Hagler of Sun Pharma shared that in the company’s late stage programs, they have not made remarkable changes. “But for early stage programs, COVID-19 has added additional elements that we need to consider. At the end of the day what we are evaluating is what programs have the highest risk adjusted net present value and that is how we are making our decisions,” he shared.
“COVID has not shifted our focus very much. However, it has intensified our attention on other aspects such as digital health and telemedicine,” said Jehan Tamboowalla of Novartis. These efforts were called for to get patients and physicians together for much needed care with focus on supporting the necessary platforms and infrastructure. “On the therapeutics side, we continued to move forward as planned,” he added.
‘What we have seen is the increased need for alternative platforms of patient physician communication,” noted Ramin Valian of Allergan. COVID-19 has impacted enrollment into the company’s clinical trials. “Overall in our minds, the pandemic has highlighted the need to focus on ways of extending therapy for patients, and long-term, new drug delivery systems that can help reduce the number of patient visits will be important for us. In addition, virtual screening and diagnostic technologies have become important and there is considerable thinking on how we can merge some of our early stage programs with these virtual platforms,” he shared and explained.
“The pandemic has accelerated our deployment of digitalization,” contributed Santen’s Peter Sallstig. “In addition, the pandemic has amplified the need for new trial designs that produce real world data, and the need for more parallel trial related activities as against sequential methods. We are also exploring electronic consents, telemedicine and remote study monitoring,” he said.
“We are all speculating on what the future will be and what are the enduring effects of COVID19,” noted Rob Kissling of Bausch + Lomb. “Compared to other businesses, ophthalmology has recovered much quicker. However, even as we try to understand the potential changes, the fundamentals of R&D and clinical development are going to be very similar,” he explained.
Finally, Dr. Robert Rothman emphasized that from the clinical and investment side we have seen significant changes due to COVID-19. “But we will continue treating glaucoma patients and focus on therapeutic options that make the most sense and allow us to treat their disease,” he concluded.
Editor’s Note: The OIS Glaucoma Innovation Showcase was held on October 15, 2020. Reporting for this story also took place during the event.