Caption: Scene as Viewed by Person with Retinitis Pigmentosa
In December 2017, news broke to great fanfare that the FDA had approved the first ever gene therapy for a genetic disease. Luxturna (voretigene neparvovec-rzyl) had been proven to restore vision in people living with inherited retinal diseases. Stories about children seeing their parents’ faces for the first time and adults putting away their white canes forever were widely circulated. As a vision rehabilitation specialist, I’ve been approached by clients who ask how they too can become pioneers in the nascent field of gene therapy. It was time to look into Spark Therapeutics Inc., the company behind the research, development, and manufacturing of Luxturna, to get some answers. Dr. Paulo Falabella, M.D., Medical Affairs Ophthalmic Lead at Spark Therapeutics, helped me understand the science behind the revolutionary treatment. I also spoke to members of the Spark Therapeutics Generation Patient Services support team about the process and the cost. For those anxious to receive treatment today, my findings may disappoint. But I can say with confidence that there are many more therapies on the horizon, and Luxturna heralds a new era for those who have lost vision to inherited retinal diseases.
Will Luxturna Work for My Particular Form of Inherited Retinal Disease?
Quite honestly, the chances are slim. As of this post, only patients with Leber congenital amaurosis (LCA) and about 4 percent of people diagnosed with retinitis pigmentosa will qualify. Over 250 genetic mutations cause eye conditions that share the hallmarks of night blindness and field loss, but this treatment is tailored to just one specific gene—RPE65. Roughly, 1,000 to 2,000 people out of an estimated 10 million in the United States can trace their inherited retinal disease to an RPE65 gene mutation. The pool of candidates is whittled down even further as physicians must determine whether each patient has enough viable retinal cells to benefit from the therapy.
What Exactly Is Gene Therapy?
Genetic diseases are the result of mutations in a gene that lead to disease in specific cells. With gene therapy, a functional gene restores the health of a mutated gene. Luxturna offers gene augmentation therapy with the addition of a healthy, normal copy of the RPE65 gene, which helps retinal cells re-establish their metabolism. Unlike gene editing, no DNA is removed.
How Does a Mutation In an RPE65 Gene Lead to Vision Loss?
In a healthy eye, light is converted into electric signals that the brain interprets through a chemical process called the visual cycle. RPE65 is responsible for creating a protein that is integral to this process. In people with an RPE65 gene mutation, the retinal cells are unable to make the protein, blocking the visual cycle. This causes a buildup of a toxic byproduct that leads to the death of retinal cells.
How Does Luxturna Work?
Luxturna is delivered to the eye tissue through a subretinal injection. It contains a solution of viruses that have been engineered in the lab. The virus serves as a vehicle that ferries a healthy copy of the RPE65 gene into the retinal cells. "So instead of carrying DNA that causes disease, we ‘infect’ the cells in a good way," Dr. Falabella explained.
Does Luxturna Really Improve Vision?
Spark Therapeutics first demonstrated the effectiveness of Luxturna in clinical trials with a multi-luminance mobility test (MLMT). Participants were scored on speed and accuracy as they walked through an indoor obstacle course that simulated real-world navigational challenges like low hanging branches, steps, and other tripping hazards. Because people with the RPE65 gene mutation have difficulty traveling in low light, the course was completed under seven light conditions simulating bright daylight to the darkness of a moonless night. A year after treatment, 27 out of the 29 participants ages 4 to 44 had dramatically improved scores and most saw improvement in just 30 days.
That was the hard science that was presented to the FDA advisory panel, but the personal stories circulating on the Internet are infinitely more compelling. Perhaps the most famous clinical trial recipient of RPE65 gene therapy is 2017 America’s Got Talent contestant Christian Guardino, who was introduced to the media as someone who was "formerly" blind.
In March 2018, 13-year-old Jack Hogan became the first person to receive treatment following FDA approval. Just two months later, he revealed in an article published by Massachusetts Eye and Ear hospital that he is able to play outside with friends after dark for the first time.
How Do I Find Out If RPE65 Is the Cause of My Vision Loss?
Eye Want 2 Know is Spark’s online resource for people who want to identify the gene mutation that caused their inherited retinal disease. This resource helps patients and their health care providers navigate the process of obtaining a genetic test. Eye Want 2 Know also features personal stories in Community Perspectives which highlight how genetic testing can lead to opportunities to contribute to research, prevent misdiagnoses, and connect with others who share the disease.
Where Do I Get the Treatment and What Does the Treatment Involve?
Patients will need to travel to one of the ten Ocular Gene Therapy Treatment Centers scattered across the US that have been approved by Spark Therapeutics. A retinal surgeon will inject a drop of Luxturna containing approximately 150 billion viruses into the eye tissue. This one-time treatment will take a week or more because the first eye will require a minimum of six days to heal before surgery on the other eye can be performed.
Even If It Is a Long Shot, How Can I Find Out If Luxturna Would Work for Me?
Contact Spark Therapeutics and connect with the Generation Patient Services team, which offers support from diagnosis to post-surgery follow-up. The team will connect with your physician and help you enroll you in the program. If you are found to be a candidate for Luxturna gene therapy, Generation Patient Services will orchestrate the logistics of treatment. Most importantly, the team will work with your insurance company and look for other ways to cover costs.
How Much Does It Cost?
You could hear the collective gasp when the sticker price of Luxturna was set at $850,000. Spark Therapeutics aimed to deflect the backlash by announcing that the company had dedicated resources to educating insurance providers about the value of gene therapy in an effort to negotiate optimal rates. Spark Therapeutics is also working with non-profit 501(c)(3) companies to find other funding streams for those on Medicaid or Medicare, which do not offer coverage, as well as for the un- and underinsured.
High costs for treatments coming out of biotech have unleashed a mad scramble in the insurance industry to come up with strategies for reigning in costs. A rebate program based on a drug’s effectiveness is being touted as one promising out-of-the-box solution by some and mocked as a weak Band-Aid approach by critics.
Of course, Spark Therapeutics is just one small player when it comes to the challenge of affixing a price tag to a priceless medical treatment. The biotech industry, insurance companies, and government leaders are going to need to match the creativity and innovation of the research laboratories to keep prices from hitting the stratosphere. Scientists demonstrated remarkable grit in their arduous quest for a viable gene therapy. Policymakers will need to muster an equal amount of fortitude and resolve as they wade into the rough waters of our current healthcare system.
Will There Be a Cure for My Type of Inherited Disease in the Near Future?
Certainly, there is hope. "Gene therapy has been around for 50 years, and this particular study that led to Luxturna had been around for 20 plus years. To cross the finish line and to bring official treatment to the public brings hope not only for patients and their families but for the research community as a whole," Dr. Falabella said.
Developments in gene therapy and cell therapy as well were already accelerating, so this breakthrough has injected rocket fuel to that upward trajectory. Research into treatments for Choroideremia and Stargardt Disease are already underway at Spark Therapeutics. To stay abreast of cutting-edge treatments, Dr. Falabella encourages people to connect with the Foundation Fighting Blindness, a nonprofit organization with a mission to drive the research that will provide preventions, treatments, and cures for people affected by retinitis pigmentosa, Usher syndrome, and the entire spectrum of retinal degenerative diseases. The Foundation now offers My Retina Tracker, a free online registry for children and adults with inherited retinal disease as well as their family members. Qualified researchers can mine the database to support their investigations or use it to facilitate clinical trial enrollments. United States residents who are enrolled in My Retina Tracker can join the Genetic Testing Study, which offers a genetic test and associated counseling typically valued at $1200 at no cost to the participant. The Foundation Fighting Blindness anticipates funding through 2019 but, as the Genetic Testing Study is a donor-supported initiative, ongoing funding is not guaranteed.
As patients and healthcare providers closely track developments in emerging medical treatments, I encourage everyone to participate in the public discourse about managing costs. Gene therapy was once the stuff of fantasy. But if we cannot make these therapies a reality for all, they might as well stay trapped in the realm of science fiction.
Additional Information About Gene Therapy and a Discussion of Its Costs
Note: Information provided through the APH ConnectCenter is for educational and informational use. It is not intended as a substitute for professional advice or treatment. Consult your physician or other professionals as appropriate for medical, legal, financial, and related advice. APH does not endorse any particular treatment, organization, or product (other than products directly sold by APH).