Each August marks Children’s Eye Health and Safety Month, a time that brings eye injuries and vision loss to light. One out of 20 children ages three to five has a vision problem that could result in permanent vision damage if left untreated. To bring awareness to childhood eye disorders and the advancements in research, we spoke with the Center for Rare Diseases’ Jessica Wessel, Clinical Strategy Lead, and Amy Raymond, Director of Therapeutic Expertise. Below, they share their experience and insights.
What is your experience and knowledge of childhood eye disorders?
JW: Prior to joining the clinical research industry, I worked clinically with a variety of patients, from pediatric to geriatric populations. Common pediatric eye diseases often go undiagnosed and can follow a patient all the way from pediatric age to adulthood. Some conditions, such as amblyopia and strabismus, will cause additional issues with the eye. I've actually experienced patients who present atomic issues and indications from the anterior chamber of the eye (the front part of the eye) all the way to the posterior chamber of the eye (the back of the eye). These issues can cover any type of refractive error all the way down to genetic issues that affect the retina or the macula in the back of the eye.
I was drawn to start a career in ophthalmology because of the gaps in access and use of eye care services. It’s one of the most rapidly advancing fields in medicine, thanks in large part to technological innovations from surgical aids, diagnostic tools, implantable devices, and pharmacology. We continue to see both a significant amount of evolution and an opportunity to continue advancing, progressing the care available to many patients in need. After having worked several years in clinics and with patients, it was really difficult for me to consider switching to the industry side. Still, I wanted to use my knowledge towards operationalizing more patient-focused studies.
My current work in ophthalmic research has not been focused on any specific age group. Prior to joining the industry, I worked in a clinic as a research coordinator and director of compassionate use, which involved pediatric, adult, and geriatric patients. My specific indication experience with pediatric patients involves strabismus, nystagmus, rare retinal disorders (achromatopsia, Retinitis Pigmentosa, and Stargardt's), Glaucoma, Aniridia, congenital cataracts, and marfan syndrome.
Working in the Center for Rare Diseases, are there certain childhood eye conditions that are particularly active areas for drug development?
JW: The industry is seeing a focus on rare pediatric retinal disorders. Some of these are biologics and the majority of them are gene therapies. Indications that we've been seeing a lot of interest in as of late are Stargardt's Disease, Retinitis Pigmentosa, Leber's Hereditary Optic Neuropathy (LHON), and Leber’s Congenital Amaurosis (LCA). However, there are multiple treatments being developed across a wide variety of indications.
What experience does PRA have around childhood eye disorders to date?
JW: For rare disease in general, ophthalmology is a growing therapeutic area in clinical research. PRA has made significant investments in our internal teams. In addition to myself as a clinical strategy lead with ophthalmology experience, our team has expanded with two board-certified ophthalmologists within our medical affairs team. With physicians in both the US and the EU, we are able to support the global landscape with local expertise. In the past two years, we’ve focused our development of training for internal teams, training for research sites, and developed a strategic approach to the timing of these trainings.
In the rare disease landscape, we truly believe that proper support and education for sites ultimately trickles down to the properly supported patients and high-quality data. Our teams modulate site level training and communication to balance engagement with projected enrollment rates. These strategies, in addition to our Managers of Patient Advocacy & Engagement within the Center for Rare Diseases, provide a wide variety of support for clinical development.
How has PRA evolved to support the development of gene therapies to treat childhood eye disorders?
AR: Certainly, the Gene Therapy Working Group has matured in recent years. This is a cross-functional team within PRA that focuses on development of gene therapies to treat rare disorders, providing support at all stages. We’re seeing gene therapies developed for lots of therapeutic areas, but there are some factors that make gene therapy especially attractive for treating eye disease. One reason is that the eyes are what we call “immune privileged.” This means that the body’s normal inflammatory immune response is limited here, which greatly reduces some of the side effects that are considerations in developing many gene therapies. The Gene Therapy Working Group necessarily has many collaborative touch-points, though. For example, since half of all rare disease patients are children, we also work closely with the Center for Pediatric Clinical Development.
Are there any specific developments in gene therapy that have helped further treatment options for children suffering from eye disorders?
AR: The most impressive example to date is the development and 2017 marketing approval of Luxturna. We all anticipate this will be just one of many gene therapies brought to market in the near future for ophthalmological conditions. Luxturna was the first gene therapy approved in the US for a rare genetic condition, specifically the ultra-rare patient population who have LCA or RP due to mutations in both copies of their RPE65 gene. Not only does this bring meaningful treatment options for the roughly 200,000 patients around the world, but just as importantly, the success of this program inspired and encouraged several other drug developers.
The science behind this treatment was decades in the making. It’s a beautiful story of thoughtfully developing brand new assessments to show the true value of a gene therapy treatment for a vision impaired patient population. The assessments that were developed and validated through the Luxturna program, such as the multi-luminance mobility test (MLMT), are ones we are all now using in other programs serving ophthalmology patient communities. Most importantly, these assessments truly take into account the disease symptoms these patients cared about: symptoms related to their activities of daily living. There are several forms of retinal blindness, with over 250 genes identified as their causes—now, there’s a playbook for going after them.
Are there any big stories in gene therapy that may help improve eye care for children and prevent disorders from progressing?
AR: Leber’s Hereditary Optic Neuropathy (LHON) has been an active space for developing gene therapies. Those studies are enrolling children to participate. With many inherited retinal diseases, our hope is to treat these kids as early as possible to limit the vision loss they will have to endure.
Gene therapies are also in active development for several inherited retinal diseases, including Retinitis Pigmentosa (RP), Choroideremia, and Stargardt’s Disease—even Achromatopsia. While it’s terrific that Luxturna is approved and available, this hasn’t stopped development of other gene therapies for LCA. In fact, as technologies improve, we’re seeing drug developers move into gene editing techniques to treat genetic diseases. One pioneering company is already testing a gene editing treatment for LCA in human trials.
For more information about these technologies, diseases, and trial options, visit the American Society for Cell & Gene Therapy.
How are PRA’s clinics helping to further the improvement in childhood eye care and safety?
JW: PRA operates three ophthalmic research clinics. Two are dedicated to single clients, one of which is a Top 10 healthcare company. The third is a PRA-owned independent clinic that works with multiple clients in California. Thanks to our partnerships and the support of PRA’s Clinical Operations staff, our clinics now manage various studies that have historically focused on contact lenses, refractive errors, and dry eye disease.
Can you speak to the global disparities that exist with regards to the eye care disease prevention and treatment options available to children?
JW: Underprivileged people in the developing world suffer far more blindness and visual impairment than those in more developed countries. This is largely due to two factors: the persistence of diseases that no longer occur in developed countries and a lack of access to ophthalmic services for those conditions that occur commonly (e.g., glaucoma, diabetes, retinopathy of prematurity, and un-operated cataract). Globally, 19 million children under age 15 are visually impaired. Visual impairment in children is a severe public health, social, and economic problem worldwide.
At PRA, we’re committed to leading the way in pediatric research. We help our clients save time and resources by determining the feasibility and effectiveness of pediatric studies at every phase of a program. Our global experience allows us to develop and execute country-specific, customized recruitment and retention initiatives to help study teams meet or exceed goals.
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