It can be devastating to watch someone slowly lose their vision.
Just ask James List, M.D., Ph.D., Global Therapeutic Area Head of Cardiovascular, Metabolism and Retina at Janssen Research & Development, part of the Janssen Pharmaceutical Companies of Johnson & Johnson. Before he joined the company in 2014, the Harvard endocrinologist spent his days counseling patients with diabetes. “Many people don’t realize that diabetes can cause irreversible damage to multiple organs, including the eyes,” he says.
The urgent need for treatments to restore or preserve vision has remained top of mind since Dr. List took on his role at Johnson & Johnson to lead a global pharmaceutical team focused on creating innovative solutions to improve the lives of those living with cardiovascular, metabolic and retinal diseases.
“We’re able to harness science and the power of the company to potentially offer hope to those living with devastating eye diseases that threaten to rob their vision,” he says. “There’s a lot of promising science—and a huge amount of unmet need.”
Indeed, the company has been hard at work, including making progress on investigational gene therapies, one of which could potentially improve vision among people with a rare genetic eye disease.
Retinitis pigmentosa (RP) is an uncommon genetic disorder that involves a breakdown and loss of cells in the retina, the light-sensitive tissue that lines the back of the eye. Up to 20% of the time, this is due to a mutated gene, RPGR, that’s passed down from the mother, resulting in a form of RP known as X-Linked RP (XLRP)—an X-chromosome-linked disorder that affects one in 40,000 people worldwide.
The disease, which mostly affects males, is usually diagnosed in adolescence or young adulthood and begins with night blindness and a loss of peripheral vision.
“Patients develop tunnel vision, where they can see directly in front of them but lose the ability to see on the side,” says Dr. List. “Over the years, that tunnel gets smaller and smaller until they become legally blind, usually in their 40s. It’s a disease with serious consequences.”
Unfortunately, there are currently no treatments available for any form of RP, which is why the Janssen Pharmaceutical Companies of Johnson & Johnson are passionate about working to uncover therapies for this disease. “Anything that we can do to slow or halt the progression of XLRP has the potential to be life-changing,” says Dr. List.
For National DNA Day, Dr. List explains this revolutionary work—what it is, how it’s done and what promise it holds.
A therapy with potential promise for retinal disease
Gene therapy is one of the ways Janssen aims to significantly improve health outcomes for patients.
During gene replacement therapy, a person is injected with a healthy gene to replace a damaged or mutated one. While the concept has been around since the late 1970s, the science is so complex that it wasn’t tried on humans until 1990. Since then, it’s been studied to treat a variety of diseases, including certain cancers, cystic fibrosis and hemophilia.
There’s a particular appeal to studying the use of gene therapy to treat inherited retinal disorders because “in these diseases, the cause is due to a single gene not working properly,” explains Dr. List.
In the case of XLRP, the gene fails to produce a protein necessary for the proper functioning of photoreceptors, the cells in the retina that convert light into electrical signals that are then sent to the brain. “The goal of the investigational gene therapy is to take a working copy of the RPGR gene and inject its DNA into the photoreceptor cells to replace the nonfunctional gene,” Dr. List says. “Once the underlying defect is fixed, hopefully the disease can be addressed, or at least any more damage can be stopped.”
The eye itself is an ideal target for gene therapy. “It’s physically accessible, and it also has ‘immune privilege,’ which means it’s able to tolerate the introduction of a foreign substance without immediately going into high alert and attacking it, unlike most other organs,” Dr. List explains. “Since it’s also very small, the amount of gene therapy required to treat it is relatively low, too.”
Potential and promise in clinical trials
In January 2019, Janssen entered into its first global collaboration with gene therapy company MeiraGTx to develop and commercialize gene therapies for the treatment of inherited retinal diseases, as well as to develop manufacturing technology.
Two things made MeiraGTx such an appealing partner: They are leaders in the field of gene therapy, and they already had very strong relationships with hospitals and medical centers that specialize in inherited retinal diseases.
“Our partnership is designed to ensure that we take advantage of the benefits both companies bring to the table, including MeiraGTx’s expertise in rare inherited retinal diseases and gene therapy combined with Janssen’s expertise in developing drugs and bringing them to the market,” says Penny Fleck, MT, MBA, Vice President, CVM Portfolio and Retinal Development, Janssen Research & Development, LLC.
Ideally, we’d like to see patients get a therapy like this as early as possible in the course of their disease—potentially as soon as they’re diagnosed. The hope is that the earlier they start treatment, the more of their vision we can improve and preserve.
This initial partnership and learnings, Fleck notes, “have enabled us to gain experience in this field, and we are extremely excited about how gene therapy can potentially be utilized to deliver life-changing therapies to patients who are either progressing to blindness or who are born with significant visual impairment where today there are no available treatments.”
To do just that, the Janssen and MeiraGTx collaboration began clinical trials to test an experimental gene therapy at specialized eye centers in the United States and the United Kingdom. Potential candidates were required to undergo genetic testing to confirm their diagnosis.
Looking toward the future of disease treatment
The next step in the partnership’s journey is to test the investigational gene therapy in a larger phase 3 clinical trial. It’s already received Fast Track and Orphan designations from the U.S. Food and Drug Administration, which can help accelerate drug development for certain serious or rare diseases.
“Ideally, we’d like to see patients treated with therapy like this as early as possible in the course of their disease—potentially as soon as they’re diagnosed,” says Dr. List. “The hope is that the earlier they start treatment, the more of their vision we can potentially help improve and preserve.”
But this is just the first rung in what Dr. List hopes will be a long ladder of pharmaceutical gene therapy treatments.
The company is also collaborating with MeiraGTx to investigate a gene therapy for the genetic retinal disorder achromatopsia, a condition in which patients cannot see colors.
In December 2020, Janssen acquired the rights to Hemera Biosciences, LLC’s investigational gene therapy treatment: a one-time outpatient eye injection to help preserve vision in patients with late-stage, severe age-related macular degeneration.
Johnson & Johnson is also leveraging its knowledge across all of its sectors to build capabilities in the manufacturing, development and commercialization of a wide range of gene therapies for other parts of the body, Dr. List says: “We’re pioneering potential solutions with gene therapy in eye disease and look forward to extending the technology to someday treat other serious conditions such as heart, liver or kidney disease.”
