Molly Troxel, who has an inherited degenerative eye disease, regained some vision after being treated with Spark’s experimental gene therapy, Luxturna. (Photo courtesy of PBS.)
This month, PBS is airing a documentary called The Gene Doctors that spotlights several emerging gene therapies, including Spark Therapeutics’ Luxturna, a treatment for a rare form of blindness that won a unanimous thumbs-up last week from an advisory panel to the FDA. In addition to tracing the history of Spark’s treatment, the film brings attention to gene therapies for cystic fibrosis, Duchenne muscular dystrophy (DMD) and an ultra-rare neurologic disease called fatal familial insomnia.
The Gene Doctors is timely, and not just because Spark is expected to nab FDA approval for Luxturna in the next few months. Last night, Gilead and its newly acquired cell therapy company, Kite Pharma, won FDA approval for Yescarta, a gene-altering treatment for some adult patients with B-cell lymphoma. It was the second gene therapy approved to treat cancer in as many months, following just behind Novartis’ Kymriah, which was approved to treat some pediatric leukemia patients.
If Spark’s therapy is approved by mid-January, as scheduled, it will represent the next generation of gene therapy. Yescarta and Kymriah, which are known as CAR-T treatments, involve removing immune cells from patients and then altering their genes so they have the ability to recognize and kill cancer. Luxturna, by contrast, is designed to correct a faulty gene that’s inherited at birth. One injection into each eye inserts a good copy of the bad gene. In clinical trials, the procedure improved most patients’ ability to see light. Some trial participants gained visual acuity, too, including teenager Molly Troxel, who is shown in The Gene Doctors riding her bike and working on puzzles.
Some of the key discoveries that led to the development of Luxturna were made at a time when gene therapy was out of favor, recalls Jean Bennett, director of the Center for Advanced Retinal and Ocular Therapeutics at the University of Pennsylvania Perelman School of Medicine. In 1999, 18-year-old Jesse Gelsinger died in a trial at Penn of a gene therapy to treat a rare liver disease. At the time, Penn scientists were preparing to test their gene therapy for blindness in dogs that inherit a similar form of degenerative eye disease as the ones now targeted by Spark’s product.
“It was a terrible time for the gene therapy field—everything ground to a halt,” recalls Bennett, who is also featured in the PBS film. “Companies that were working on gene therapies went bankrupt. It was a very difficult time to try to get funding for gene therapy studies.” Backed by grants from the Foundation Fighting Blindness and the National Institutes of Health, the Penn team began testing gene therapy in dogs in the early 2000s.
The results were astounding, says Bennett, who adopted some of the dogs involved in the research, along with her husband, Albert Maguire, a retinal surgeon at Penn. One of those dogs, Venus, is shown in the film playing and leaping over obstacles after receiving the gene therapy. “When I first met her, she was 2 years old she would cower in the back of her dog run because she couldn’t see somebody reaching out to touch her, so she would freak out,” Bennett says. “After her first injection, her whole behavior changed. She was so happy and active. It was miraculous.” Venus, a Swedish Briard, later had her second eye injected and is now 10 years old. (Breeders of Swedish Briards have largely succeeded in eliminating the faulty gene through selective breeding, Bennett notes.)
Bennett treated 20 patients in the human trials, many of whom experienced significant vision gains, she says. “Some can read books without being dependent on Braille,” she says. “Some are applying for driver’s licenses. It has really transformed their lives.”
At the FDA review meeting last week, advisors to the agency were asked to consider whether or not there’s enough evidence to show that Luxturna’s positive effects are durable. It’s a legitimate concern, particularly because some analysts are predicting the therapy could cost as much as $1 million. The FDA wondered if Luxturna would need to be administered more than once to maintain vision gains.
Bennett, who attended the meeting, said the panelists looked at three years worth of data and were comfortable with the results. “I think the panel agreed that people are maintaining their gains,” she says. “So far it looks like it’s durable with one injection per eye.”
Nearly 20 years after the Gelsinger tragedy, there are now more than 1,000 gene therapies in the pipeline targeting both cancer and inherited diseases. For Bennett, it’s satisfying validation of the contributions made by scientists, physicians and trial participants—both canine and human—to a field that had been all but abandoned.
“Out of that very sad phase, the gene therapy field matured. Safety got ratcheted up in a way that was appropriate,” Bennett says. “With the data from the [Luxturna] trial and the recent approvals of CAR-T cell therapies, I think it’s the most exciting time ever for gene therapy. I’m really optimistic studies here and elsewhere will lead to treatments for diseases that until now have been untreatable.”
The Gene Doctors is streaming online all month here and airing on PBS stations around the country. It will be available for streaming on Amazon starting in November.