Please can you give a brief overview of wet age-related macular degeneration (AMD)?
Wet AMD is characterized by abnormal growth of blood vessels in the macula (the area of the eye containing vision-enabling photoreceptors), and is responsible for the vast majority of severe vision loss in the industrialized world.
If left untreated, it can lead to the rapid deterioration of visual acuity and blindness. While there is no cure for wet AMD, the expense and burden of current treatment methods have driven the development of novel approaches, such as the Oraya Therapy.
What treatments are currently available for wet AMD and how effective are they? Why is wet AMD particularly difficult to treat?
Prior to approximately 1999, the primary therapeutic alternative was to use a laser to destroy the neo-vascular incursions. This therapy had the potential to slow the disease progression, but at the cost of immediate vision degradation.
In roughly 2001, photodynamic therapy (PDT) became a treatment alternative, involving the injection of a photosensitive drug systemically, and then activating the drug with a diode laser targeted in the eye.
For some sub-populations of patients, this showed an ability to preserve or slow the loss of vision, but without any recapture of the previous vision loss and with the need for multiple repeated treatments over time.
Both laser and PDT continue to be used on a limited basis for certain patients or in various geographies, but the major breakthrough occurred in roughly 2005 with the introduction of intravitreal injections of a pharmaceutical agent (anti-VEGF) to halt the formation and progression of the neovascular vessels.
This therapy, in numerous well controlled and managed clinical studies, has been shown to enable recapture of meaningful vision in many patients while also slowing the rate of disease progression.
However, in order to achieve optimum results, anti-VEGF therapy requires very frequent monitoring of the patient in the clinic, and chronic use of anti-VEGF injections at a rate of 6-8 times per year in the typical patient.
Because of the burden, cost and intensity of this anti-VEGF regimen, real world patient outcomes are not achieving the promise shown in clinical studies.
In published results from around the world, it is evident that patients are routinely under-treated, and that early vision gains are typically lost and further vision loss experienced over the ensuing 2-4 years of therapy.
Patient compliance, insurance cost or access controls, and physician and facility infrastructure constraints all serve to limit the practical and sustainable use of the prescribed clinical regimen. As a result, patient outcomes are, on a whole, substantially worse than shown in the controlled clinical studies.
Oraya has developed and clinically validated a non-invasive low energy radiation treatment, intended as a one-time therapeutic intervention, with the potential to maintain or enhance vision outcomes with substantially fewer anti-VEGF injections.
In Oraya’s INTREPID study, the target patient population in the active arm of the study (patients receiving Oraya therapy) showed equal or better vision outcomes to the control arm but with approximately 50% fewer injections, and with 25% of the population needing no further injections out to 2 years.
In real world clinical use, this intervention has the potential to make a significant and positive impact on vision preservation, especially for patients unable or unwilling to maintain the prescribed regimen of anti-VEGF mono-therapy.
Oraya is now offering this therapy on a commercial basis in Germany, the UK and Switzerland, and with additional sites and countries in the commercial pipeline.
It was recently announced that Oraya will be collaborating with scientists at Dana-Farber Cancer Institute to develop a new treatment for wet AMD involving gold nanoparticles. Please can you outline how this collaboration came about?
Dana Farber researchers have been investigating the use of gold nanoparticles in the treatment of cancer for some time. They came upon some of Oraya’s work at a medical physics conference and realized the tremendous potential in using nanoparticles to treat AMD with the low-energy X-rays used by the Oraya system.
There are a number of key advantages in working with AMD over oncology.
1). Oncology uses much higher energy photons that penetrate deep in the body, but as a result of some interesting physics have a much lower dose enhancement with gold nanoparticles than do the 100 kVp photons used in Oraya therapy.
2). Measuring the concentration of gold nanoparticles deep in a tumor is challenging but important in order to understand the dose delivered. In contrast, with the eye you can just look inside! There are imaging techniques that should allow very accurate assessment of concentrations.
3). AMD is a localized disease in which we aim to destroy capillaries that fuel the progression. In contrast, cancer can be a diffuse disease and you must kill every cell for control.
Why will the research be using gold nanoparticles as opposed to other kinds of nanoparticle?
Gold is a very dense element with a high atomic number, so it is uniquely able to absorb X-rays at the energy Oraya uses.
After gold has absorbed the X-rays, it re-emits the energy in the form of electrons that have an extremely limited range. This confines the radiotherapy effect to a few cells near the nanoparticle.
In addition to exhibiting the proper physics, gold nanoparticles are biologically benign.
How will the gold nanoparticles home in on the diseased lesions in the eye?
Two mechanisms allow nanoparticles to home in on the diseased lesions. The first is their size. Normal, healthy, capillaries that feed the retina have very tight junctions between cells to prevent pathogens or large molecules from entering the retina. This is part of the blood-brain (or blood-retina) barrier. Nanoparticles in these healthy capillaries will flow through— they are too large to infiltrate the tissue.
Neovascular capillaries, on the other hand, have loose junctions between cells that leak blood and fluid into the surrounding tissue. Nanoparticles will escape from the capillaries into the tissue and accumulate where the capillaries are the leakiest— exactly where we want to treat.
Nanoparticles “tagged” with proteins that preferentially stick to diseased tissue is a second mechanism under investigation. The investigators will study tagged and un-tagged versions to determine the relative effectiveness of each.
How will the nanoparticles then treat these diseased regions?
The Oraya system will be used to deliver X-rays after the nanoparticles are located in the volume surrounding the leaky neovascular capillaries. Because of the way the nanoparticles absorb X-rays and re-emit electrons, we expect to find a localized dose enhancement of between 3 and 8 times what the X-rays alone deliver.
Because the dose enhancement is limited to such a small area around the nanoparticle, healthy tissue surrounding the CNV complex will receive the non-enhanced dose, while the targeted capillaries will see the much higher dose.
Is this process likely to damage surrounding tissues?
We have already demonstrated that the Oraya therapy is extremely well tolerated. Because the nanoparticle dose enhancement is limited to a few cells surrounding the nanoparticle, no damage to the surrounding tissue is expected.
If this research is successful, will the technique be tested on other cancers?
Oraya’s focus is clearly the eye. However, the findings could have broad implications for cancers throughout the body. As one of the world’s premier cancer institutes, this is a significant interest for Dana Farber.
Research on the use of gold nanoparticles in the treatment of cancer has been on-going for some time in many institutions.
The reason this work is so exciting is that the energy of the Oraya X-ray therapy is ideally suited for dose enhancement, and the eye is an ideal platform for viewing and understanding the distribution of nanoparticles in living tissue.
The findings will be important for much more than just AMD, and could lead to novel methods of cancer treatments.
What are Oraya’s plans for the future?
Oraya’s immediate and primary focus is on the ongoing commercialization and evolution of the Oraya Therapy for the treatment of wet AMD.
We anticipate significant expansion of our European business, and potential entry into select Asian markets over the next 2-3 years.
With respect to oncology, the Oraya delivery system is well suited for precise delivery of low energy radiation into the eye, and the use and/or adaptation for use in ocular cancers would be technically and clinically straightforward. These applications are secondary to Oraya’s focus on the wet AMD market opportunities, but may be of more immediate interest to researchers and companies already in the oncology markets.
About Jim Taylor
Jim Taylor brings over 30 years of experience and leadership in the medical device industry. Prior to joining Oraya in 2009, he served as president/CEO at sector leading companies including Carl Zeiss Meditec, Inc. (CZMI), Coherent Medical and Ohmeda Medical Systems.
At Coherent and subsequently at CZMI, several landmark technologies in eye care were launched, including optical coherence tomography (OCT) imaging systems and photo dynamic therapy (PDT) lasers for AMD diagnosis and treatment, as well as an array of other technologies for glaucoma, refractive and cataract applications.
His prior experience includes senior roles in leading providers of CT and Ultrasound imaging, Critical Care, Cardiac Monitoring, and Anesthesia Delivery systems.
Taylor received his Bachelor of Science degree with honors from the United States Naval Academy and holds a master’s degree in administrative science from Johns Hopkins University.
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