The Ophthalmology Innovation Summit (OIS) is one of our go-to resources to keep abreast of the newest news — the coolest companies, the neatest treatments, and so on. The “Innovation” part of the title should give you a clue as to what the group is all about, and the “Summit” part may be a double entendre, since they show the industry at its peak. That’s certainly what they intended, right? Wink, nudge, and all that.
The most recent showcase was the OIS European Innovation Showcase, presenting information on some of the continent’s most forward-thinking companies. That’s what we’ll examine today. If you’re looking to keep in touch with the most compelling trends in European ophthalmology, you’ve struck gold right here. We’ll go through the companies that presented at OIS chronologically.
Visotec GmbH
First up was Helge Sudkamp, CEO of Visotec GmbH (Lubeck, Germany). Visotec’s goal is to make optical coherence tomography (OCT) accessible for everyone, everywhere. As Mr. Sudkamp noted, this requires two changes. First, devices need to be portable, able to be used anywhere. Second, the data needs to be interpreted — in this case by artificial intelligence (AI).
To wit, they’ve created proprietary full-field OCT technology using devices that are small, handheld, and inexpensive. They’re easy to use, and can be operated with the push of one button — and only take one second per OCT volume. The second part, however, is where the real innovation begins — the data is transferred to cloud-based AI diagnostics. Both systems are currently fully functional.
The tech is currently clinically proven. In a study of 88 eyes of age related macular degeneration (AMD) patients, there was an 85% success rate using the device. The first major application of the device will be for neovascular AMD (nAMD), allowing patients to conduct daily measurements at home, helping prevent vision loss.
Visotec offers the product as a subscription-based model, with monthly recurring payments for the patient. Because data goes directly to the cloud, this is an easily scalable model. The model leads to wins across the board, including for patients, physicians, pharma, and insurance. And the payoff? Potentially huge. As Mr. Sudkamp noted, the total potential market in Europe and the United States is around $5 billion.
A combination of AI, cloud, and home device is a model that may work for many other conditions. Watch that space for further developments.
GenSight Biologics
Dr. Magali Taiel, the chief medical officer of GenSight Biologics (Paris, France), spoke on the company’s behalf. They’ve created a drug called Lumevoq® to treat Leber Hereditary Optic Neuropathy (LHON), the most common mitochondrial disease — but rare overall — which can cause bilateral blindness in the prime of life, between 15 and 35 years old. It mainly affects men.
The REFLECT phase III study was a double-masked, randomized vs placebo IVT study of 98 students at 13 centers. Some patients received bilateral Lumevoq, while others received unilateral Lumevoc and a placebo.
The results were quite positive: Eyes treated with Lumevoq all had statistically significant improvements in best corrected visual acuity (BCVA) compared to the placebo-treated eyes. Worth noting is that bilaterally treated eyes improved more than unilaterally treated eyes, indicating somewhat of a systemic improvement. Even in unilaterally treated patients, the placebo-treated eye showed some BCVA improvement. In each group, the eyes’ improvement tracked together.
A bilateral treatment seems to be the way forward for using Lumevoq due to the contralateral effect. Also worth noting? The safety profile of Lumevoq is favorable. That’s good news. Look forward to a potential commercial launch in 2022 in Europe as well as a US FDA biologics license application (BLA) in the same year.
Brill Pharma
Ramon J. Pons joined us to speak about Brill Pharma (Barcelona, Spain). He’s their business development director, and Brill is a focused ophthalmic company with a presence mainly in Spain, Portugal, and Malaysia.
Mr. Pons shared the results of Brill’s first project — a corneal esthesiometer. It’s a worldwide patented product, available in Europe in Q4 2021 and in the US in Q1 2022. It’ll be presented by the American Academy of Ophthalmology (AAO), so we’ll look forward to that.
The Brill Engines device will be portable and non-invasive, will use ambient air as the stimulus, and will give a high degree of precision while remaining simple to use with default options. As Mr. Pons indicated, their device provides significant benefits over Cochet-Bonnet or Belmonte devices. It’s valuable for diagnosing all sorts of pathologies, so it’s a really well-rounded tool.
The device can provide five levels of stimulation, can maintain constant pressure air pulses, doesn’t rely on a pressurized air cartridge, and can be used in a slit lamp or be hand held. It’s also able to provide reproducibility of the air discharge and comes with an electronic positioning system consisting of a camera and two LEDs — and is battery-operated and rechargeable.
Keep an eye out for this tool coming in the next several months. It should be a valuable one and can replace bulkier or less reliable esthesiometers.
Pixium Vision
Pixium Vision’s CEO, Lloyd Diamond, helped introduce us to his company and their work. Pixium is a publicly traded company based in Paris. They’re developing a bionic vision system called Prima, which targets vision restoration in patients who suffer dry AMD. It’s a miniaturized, photovoltaic, wireless sub-retinal implant, implanted underneath the retina in a surgical procedure. The proof of concept has been established — and the whole concept is pretty breathtaking.
The company was established in 2011, with neuromodulation in ophthalmology their prime focus. If you’re ready for a technology word salad, here goes: Pixium is “leveraging proprietary algorithms and artificial intelligence to develop bionic vision systems for the treatment of retinal dystrophies.” Essentially, they’re using AI to link brain and machine. This results in the Prima Retinal Implant System, which helps visually impaired patients regain sight through neuromodulation.
That’s pretty darn cool, and it sounds like it’s from the future. But the future is now, and this treatment is underway. They’re entering the final development stage with Prima — so far, 7 patients have received treatment from it. Pixium believes their Prima system can become the first therapeutic solution for dry AMD. If so, that’d be a landmark change as dry AMD currently has no treatment.
Pixium’s PRIMAVERA pivotal study in dry AMD is currently recruiting, and expects a read-out in late 2022. They’ve initiated a U.S.-based early feasibility study in Q1 of 2020. So, the company is making big steps, and those steps may make huge waves in the future.
Re-Vana Therapeutics
We’re happy to cross paths with Re-Vana Therapeutics’ CEO Michael O’Rourke again. Re-Vana Therapeutics (Belfast, UK) was founded in 2016 and is associated with Queen’s University Belfast, but is also incorporated in the U.S. Their main focus is extended-release biologics — which may result in a “Holy Grail” of treatment options in the form of photo-crosslinked ocular therapeutics.
The “Holy Grail” in this case would be a 6 month+ sustained-release office-based biologic to the retina. They’ve achieved preclinical in vivo proof of concept, and their novel technology enables tunable delivery of biologics and small molecules. They’ve attracted both strategic pharma collaborators and sophisticated ophthalmic investors. Their tech is also well-protected with robust IP.
The main challenge Re-Vana is undertaking is the challenge of delivering ocular therapeutics. The idea is to have the same platform to deliver both small molecules and the currently available biologics.
The company’s “secret sauce,” as Mr. O’Rourke put it, is a polymer blend with tissue-like properties combined with a controlled release of a drug from a polymer mesh. This leads to a biodegradable implant that provides sustained drug delivery at a therapeutic level, all while providing stability, high drug load, and eye tolerability.
Re-Vana currently has two platforms: EyeLief®, which is a photo-crosslinked prefabricated implant ideal for molecules that require a release rate of 1-3 micrograms per day. The second platform is Oculief, a gel-based system that’s photo-crosslinked in situ and is ideal for molecules that require a higher release rate, i.e. north of 10 micrograms per day. Both of these platforms are built for 6+ months of service, with OcuLief® potentially serving up to 12 months. OcuLief is available for strategic collaboration with large pharmaceutical companies for novel biologics.
These implants can be implanted in an office with small-gauge needle applicators. If our instincts are right, this could potentially end up being a game changer for both patients and doctors. Reducing the need for injections of anti-VEGF agents and regular ophthalmic trips could potentially rewrite a large part of the industry. We wish Mr. O’Rourke and Re-Vana the best.
Recornea
Recornea (Udine, Italy) is a pre-clinical stage medtech ophthalmic company developing therapeutic corneal implants for keratoconus. Their CEO, Emiliano Lepore, introduced the company and provided a valuable overview of what being a keratoconus patient would look like. Just how would it look, you ask? Blurry. It looks blurry.
There are some 218 million eyes affected worldwide according to Mr. Lepore, with some 1.8 million new eyes to be treated every year. That means big business, and lots of money.
There’s plenty of room for improvement in keratoconus treatments, too. As Mr. Lepore pointed out, intracorneal ring segments are ineffective in at least 50% of keratoconus cases. If keratoconus goes too far, it can force the need for a corneal transplant — a procedure that has plenty of its own complications, including wait times.
Recornea’s solution is the first nitinol corneal implant to treat keratoconus — the GROSSO implant, which has the same curvature as the eye’s natural physiological curvature. The implant will be in direct competition with intracorneal ring segments and as a complementary treatment to crosslinking. GROSSO will be designed to improve vision of mid/late stage keratoconus, whereas crosslinking can limit progression of early/mid stage keratoconus.
The device is fully developed, and has received an Italian patent which has been extended in eight countries, including the EU (not a country, we know), the U.S., Canada, Brazil, Israel, India, China, and Japan. Talk about market penetration.
They’ll be beginning with patients at stage 3 and 4 of keratoconus, and then will extend their reach to patients in stage 2. This will cover 80% of the keratoconus patient market. Pre-clinical studies have validated the product design. This is potentially great news for both ophthalmologists and keratoconus patients around the world. Way to go!
Radiance Therapeutics
Dr. Laurence Marsteller is the CEO of Radiance Therapeutics (Tucson, Arizona, USA), which is commercializing a new ophthalmic medical device for glaucoma. Dr. Marsteller noted that the device is in an advanced state of therapeutic development, and randomized, controlled trials have proved its efficacy.
Dr. Marsteller pointed out that glaucoma drainage surgeries like trabeculectomy and MIGS have unacceptably high failure rates due to scarring. As he put it, the body views the drainage site as a wound and triggers a healing response. By 3 years, 50% of the surgeries are no longer effective as the bleb has scarred the fistula shut. Scarring of the bleb restricts fluid flow, increases IOP, and leads to blindness.
Similarly, trans-scleral MIGS have a 53% failure rate at 3 years and a 59% scarring rate at 4 years. Additionally, at 6 months post-op less than 1 in 4 eyes were deemed absolute successes. Interventions were required in nearly 20% of all eyes. Those aren’t great numbers, so something has to be done.
Radiance Therapeutics’ solution is the RadianceTX Beta Ophthalmic System™, which provides a device-based anti-scarring prophylaxis. Beta therapy is the use of a sealed source radioisotope brachytherapy that provides therapeutic energy. The device is held on the surface of the conjunctival bleb for 30 seconds. It’s easy to use and is non-invasive.
Dr. Marsteller noted that beta therapy’s well documented antimetabolite effect downregulates Tenon’s capsule fibroblasts. Using low-dose beta radiation reprograms the p53 expression on a highly localized level to reduce postoperative scarring.
Four randomized controlled trials have been completed and published in peer-reviewed journals. Beta radiation was shown to be significantly more effective than a placebo, with a 5% failure rate with beta radiation at 1 year as opposed to 30% in placebo. At 3 years, the failure rate only climbs to 10% with beta radiation, as opposed to 50% in placebo. Furthermore, beta therapy eyes were shown to be 3.2 times more likely to have a functioning bleb as opposed to mitomycin-C (MMC) treatment, and 5.6 times more likely to have IOP less than 16 mmHg on no medication versus MMC treated eyes. Patients are now being treated electively at Moorfields Eye Hospital in the UK.
Aerie Pharmaceuticals
Aerie Pharmaceuticals (Bedminster, New Jersey, USA) is known for Rhopressa® and Rocklatan®, two IOP-lowering products. That’s how David A. Hollander, the company’s chief research and development officer, framed his company, and it’s a pretty good start. The company is following a robust globalization plan, with a glaucoma franchise approved in Europe, and a licensing agreement with Santen for the above-mentioned treatments.
The company has plenty more in its pipeline too, including an AR-15512 TRPM8 agonist for dry eye, a sustained-release retinal implant platform, and an anti-inflammatory. Now that’s a company with ambition, right there.
Mr. Hollander believes the company’s new plant in Ireland will be able to produce plenty more of their product to tap into the large glaucoma market in Europe. And this is potentially big news — a 90-day efficacy and a 6-month safety trial demonstrated non-inferiority of Roclanda® (Rocklantan) to a fixed-dose combination product in Europe (Ganfort®). Roclanda achieved around 9 mmHg reduction in IOP — a pretty solid number.
As Mr. Hollander put it, the dry eye market in Europe is far less mature than that in the United States. Artificial tears remain the main treatment for dry eye in Europe. So, Aerie’s TRPM8 agonist could be a very valuable treatment for dry eye — both for patients and for the company’s bottom line.
Similarly, Aerie’s proprietary drug delivery platform for retinal disease could lead to a host of benefits, including customizable drug elution, long treatment duration and reduced injection frequency, and a greater diversity of drug targets via small molecule drugs.
Keep your eyes open for Aerie, because they’ve got their sights set on big goals.
Lumithera
Dr. Clark E. Tedford, president and CEO of Lumithera (Poulsbo, Washington, USA), introduced us to his company. For reference, he’s been involved in pharmaceutical and medical device development for more than 30 years across all sorts of different companies. So, we’re looking at a true industry veteran here.
The gist of Dr. Tedford’s talk centered around the Valeda® light delivery system, which uses a targeted photoceutical approach to treat ocular disease and damage. It’s a non-invasive, multi-wavelength photobiomodulation treatment for dry AMD, diabetic retinopathy, macular edema, and glaucoma. To date, the company’s focus has been on dry AMD.
Valeda has an elegant and versatile device design with a small footprint that can easily fit into an office or an exam room on an adjustable table. The treatment consists of a four-minute procedure per eye, meaning both eyes can be treated in less than ten minutes. No pupil dilation is required and patients can go back to their daily activities after the treatment. The retinal tissue is stimulated over a course of nine treatments administered over 3-4 weeks on a flexible schedule. Stimulating the tissue improves the health of the cell and provides benefits in both vision and underlying pathology. As Dr. Tedford noted, repeat treatments can lead to extended benefits up to 6 months or beyond in some patients. He recommends a follow-up at four to six months to see if more treatment is needed.
This kind of treatment is already FDA approved for many other treatments, including arthritis, sports medicine, and other areas that require recovery and reduced inflammation.
The model Lumithera is working with relies on a low-cost capital investment for doctors and a pay-per-treatment model for patients to support the length of trials needed for degenerative eye disease. This model has been validated in Europe and South America, said Dr. Tedford.
The company has multiple pathways for Valeda to reach commercialization, both in Europe and the U.S. The LIGHTSITE III trial in the U.S., for example, anticipates US FDA approval of Valeda for dry AMD treatment in 2022. The company has already launched a U.S. pilot study for DME treatment as well, and a post-market AMD study is underway in the European Union.
Results from Valeda have been very promising so far. For a treatment that is non-invasive, safe, and fast, it’s potentially excellent news across the board.
Samsara Vision
Tom Ruggia is another familiar face, and we’re happy to hear more from him about Samsara Vision (Saratoga, California, USA). The company is dedicated to bringing vision and freedom back to those suffering from late-stage AMD. As Mr. Ruggia noted, 200 million people are living with AMD today, and by 2040 predictions estimate the number will balloon to some 290 million. Currently, more than 10 million people are living with late-stage AMD — either dry or wet.
Three million people are appropriate for Samsara’s SING IMT the company is bringing to market in Europe. This is based on the first generation implantable miniature telescope (IMT), a technological breakthrough with excellent outcomes. That device had 700 implants worldwide, and was both CE and FDA approved. It led to dramatic quality of life improvements and was featured in 14 peer-reviewed articles. It brought four lines of vision back to almost 50% of patients, and 3 lines of vision to 70% of patients in a previous study.
This first generation had some limitations, however. The surgical procedure was highly invasive, requiring a 12 mm incision and 12 sutures. It was technically challenging as well, with adoption limited to only the best cornea-trained surgeons. And there was a 60-minute operating room time, which impacted clinicians economic returns.
The new SING IMT improves on many of these issues. Its small incision delivery leads to a less invasive surgery, with improved healing time. The foldable wing design has a self-aligned fixation and comes in a preloaded system with an injectable syringe.
The goal here is to allow much broader commercialization than the first generation because, simply, it’s easier to use and is a much less risky procedure. So far, there have been 11 procedures completed dating back two years, and the average procedure time was 20-25 minutes. That’s a huge improvement on the full hour the previous procedure took. Additionally, the 11+ sutures previously required are down to 3-4 since the incision size is now 6.5-7.0 mm. Furthermore, visual results can be achieved in 1-3 days instead of the previous 7-21.
The new design has CE certification as of April 2020, and will be commencing an FDA PMA-S trial in 2021.
Giving vision back to those who are at risk of losing it is one of the most laudable goals in medicine, we think. Kudos to Mr. Ruggia and everyone at Samsara for their work.
Feeling Breathless Yet?
Phew, so there’s a (not-so) brief overview of some of the most vital developments happening in European ophthalmology. Pretty impressive, no? Each and every one of these treatments sounds like something out of science fiction in one way or another, but they’re all very real and they’re all right here.
Many thanks to the OIS for giving these companies a platform to share their news. We can’t wait for the next time. Until then, au revoir, adios, auf wiedersehen, and so on.
Editor’s Note: The OIS European Innovation Showcase was held on July 20, 2021. Reporting for this story took place during the virtual event.
