It didn’t happen overnight, but gene therapy has officially arrived.
On Tuesday morning, the U.S. Food and Drug Administration announced its approval of Spark Therapeutics’ Luxturna (voretigene neparvovec-rzyl) a one-time treatment for adults and children with an inherited retinal disease (IRD) that can lead to progressive vision loss and blindness.
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It’s a historic moment for many in the industry, including FDA Commissioner Scott Gottlieb who has overseen the approval of two others gene therapies, Kymriah and Yescarta, in the past five months.
“The culmination of decades of research has resulted in three gene therapy approvals this year for patients with serious and rare diseases,” Gottlieb said in the agency’s media advisory. “I believe gene therapy will become a mainstay in treating, and maybe curing, many of our most devastating and intractable illnesses.”
Despite the recent precedent, Luxturna has claimed a number of important firsts.
It’s the first gene therapy to target a disease caused by a single faulty gene, RPE65. (Kymriah and Yescarta program the immune system to destroy cancer.) According to the FDA advisory, approximately 1,000 to 2,000 individuals in the U.S. have mutations in both copies of the RPE65 gene. This inhibits the production of a protein the retina needs to convert light into an electrical signal for the brain to interpret.
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A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.
Spark’s therapy is also the first to employ an adeno-associated virus vector. These are small virus ‘cargo ships’ that can be engineered to carry a specific section of DNA into the target cells. In this case, the virus inserts a normal copy of the RPE65 gene into retinal cells, so the eye can produce the missing protein.
It’s exciting technology and the culmination of decades of scientific work. Unsurprisingly, it’s also expected to be expensive. A Spark spokesman told STAT News that the list price won’t be disclosed until early January — a move that may be designed to help stakeholders slowly acclimatize to the cost. In the meantime, analysts are speculating that the one-time fee could reach six figures.
Luxturna is not a cure, but it demonstrated a high response rate and good durability in a condition with no other pharmacologic options. It also validates the technology, fueling the possibility that such therapies could soon treat other single-gene disorders, such as cystic fibrosis and sickle cell anemia.
The clinical trial program included 41 participants, with vision loss ranging from mild to advanced. Patients as young as four were treated, alongside adults up to 44 years of age.
In the Phase 3 trial, 93 percent (27 of 29) of all participants experienced a “gain of functional vision,” referring to a person’s ability to independently perform everyday activities that require some degree of eyesight. The study results were published in the Lancet.
Principal Investigator Stephen Russell of the Stephen A. Wynn Institute for Vision Research at the University of Iowa said improvements were seen in a variety of tests.
“The data show clinically meaningful and statistically significant improvements in ability to navigate independently in low to moderate light conditions, as well as marked improvements in full-field light sensitivity and peripheral vision,” Russell said, according to a Spark statement. “As a treating physician, it’s exciting to see these types of results in a disease area where no approved pharmacologic treatment options currently exist.”
The unmet need qualified Luxturna for the regulatory trifecta of priority review, breakthrough therapy designation and orphan drug designation. Spark also received the 13th Rare Pediatric Disease Priority Review Voucher, issued by the FDA to incentivize work on rare pediatric diseases. Just 24 hours ago, Ultragenyx sold its voucher to Novartis for a cool $130 million. A voucher can be exchanged for priority review of any drug in the company’s pipeline — an alluring prospect when competition is tight.
Such incentives may help, but at the end of the day, complex science just takes time.
It seems fitting then, to finish with the words of former President Bill Clinton, announcing the ceremonial completion of the Human Genome Project on June 26, 2000.
“Today, we are learning the language in which God created life. We are gaining ever more awe for the complexity, the beauty, the wonder of God’s most divine and sacred gift. With this profound new knowledge, humankind is on the verge of gaining immense, new power to heal. Genome science will have a real impact on all our lives — and even more, on the lives of our children. It will revolutionize the diagnosis, prevention and treatment of most, if not all, human diseases.”
The initiative laid the groundwork for all genome-based therapies, though the path to the market was much longer than Clinton, and many others, anticipated.
Photo: Getty Images
