Ophthotech is a biopharmaceutical company committed to developing therapeutics and gene therapy solutions to treat retinal diseases. The company is aggressively pursuing therapies for orphan conditions like retinitis pigmentosa (RP), Stargardt disease, and Leber congenital amaurosis (LCA), as well as common indications such as wet and dry age-related macular degeneration (AMD).
Most impressive, the company is taking on a multi-track strategy that includes retinal gene-therapy development, including delivery of over-sized genes and design of a two-step process of gene knockdown and replacement for autosomal dominant conditions.
While these are the scientific challenges that keep most retinal researchers awake at night, Ophthotech thrives on them and sees them as opportunities to meet significant unmet medical needs for people with retinal diseases.
Kourous Rezaei, MD, the company’s chief medical officer, says his team’s clinical and drug-development expertise, as well as its strategy of scientific collaboration, enables Ophthotech to break through these formidable technical barriers.
“One point that differentiates us from other companies in this space is that retina specialists are part of our management team,” says Dr. Rezaei. “When retina specialists are directly involved in the process of drug development, they provide an additional perspective on a number of challenges, including the design of the clinical trial. We believe this gives Ophthotech a strategic advantage.”
“Ophthotech is currently collaborating with scientists to develop novel gene delivery technology that uses adeno-associated viruses (AAVs),” adds Dr. Rezaei. “The safety profile of AAVs in humans is relatively well-documented compared to other gene therapy technologies currently in development. We are particularly interested in AAV-based delivery systems that can be modulated to target specific retinal cells.”
AAVs are engineered by scientists to deliver therapeutic genes into patients’ cells, including those of the retina. Nearly 20 clinical trials for AAV-based retinal therapies are underway. LUXTURNA™, which uses an AAV for retinal delivery of the gene RPE65, became the first FDA-approved gene therapy for the eye or an inherited disease in December 2017. However, the AAV technology used in LUXTURNA™ is now more than a decade old.
Dr. Rezaei continues, “The potential to achieve an extended treatment effect and possibly a cure through a single gene therapy administration is particularly appealing to patients who do not have any treatment options available to them, as well as to patients with age-related retinal diseases who may require chronic therapy over years, if not decades.”
Ophthotech is gaining access to emerging, cutting-edge AAV treatments through academic partnerships. It is collaborating with scientists at the University of Florida and University of Pennsylvania to advance a gene knockdown and replacement therapy for patients with autosomal dominant retinitis pigmentosa (adRP) caused by mutations in the gene rhodopsin (RHO). Earlier research for this program was funded by the Foundation Fighting Blindness. A recent paper in the journal Proceedings of the National Academy of Sciences highlights the success of the Florida-Penn team in canine studies of the RHO gene therapy. The company is planning to launch a clinical trial for RHO gene therapy in 2020.
Ophthotech also recently formed a partnership with the University of Massachusetts Medical School for developing gene therapies that deliver smaller versions of the genes for CEP290 (for LCA) and ABCA4 (for Stargardt disease) ¾ genes that are otherwise too large for existing AAV delivery systems.
“Our expertise is clinical development and its timely execution,” says Dr. Rezaei “Our strategy is to collaborate with universities and companies who have very strong science, and use that science with our clinical expertise to develop novel therapies. Our team has significant ophthalmic drug development experience and deep relationships with global ophthalmology thought leaders. We have an extensive network of clinical trial sites in ophthalmology, having worked with over 250 sites worldwide.”
Ophthotech also has other clinical trials underway for Zimura®, the company’s product candidate that is designed to target and inhibit complement factor C5. While the complement system plays a critical role in fighting off infection and pathogens, it is implicated in accelerating the progression of certain retinal diseases when not properly modulated. The company’s Zimura clinical trials for people with Stargardt disease, as well as dry and wet forms of AMD are all in Phase II.
The Foundation Fighting Blindness has been a valuable resource for the Zimura clinical trial for Stargardt disease by providing access to natural history data from its ProgStar study, and patient information from www.MyRetinaTracker.org, the Foundation’s global patient registry. If you or someone you know are interested in participating in this clinical trial evaluating Zimura for the potential treatment of Stargardt disease, please call 1-833-STGD1-OP (833-784-3167). Information on all Zimura clinical trials can be found at www.clinicaltrials.gov.
“When we design a clinical trial, we need to know the natural history of the disease, the patients who could potentially be helped the most, and the optimal endpoints for the trial to determine if a treatment is working. These factors may ultimately determine the success of the clinical trial,” says Dr. Rezaei. “With ProgStar, the largest natural history study ever done in patients with Stargardt disease, we were able to use the study results to help design our clinical trial. If the Foundation had not been there, it would have been more difficult, and may not have even been feasible, to design our trial.”