After decades of unfulfilled promises and setbacks, the field of gene therapy broke through with three FDA-approved products last year, ushering in what is likely to be a rapid escalation of new treatments for some of the rarest and most debilitating diseases.
“Part of the idea of the Human Genome project was that once we had the identity of all the genes, it would be important and straight forward for us to development more therapeutic options for people with serious inherited diseases, said Katherine High, M.D., president and director of research and development for Philadelphia-based Spark Therapeutics. “But it turned out this took a little longer to do than the Human Genome project.”
Speaking on a panel at Health Journalism 2018 in Phoenix, High said that while gene therapy is a very simple concept, it is arguably one of the most complex types of therapeutics that people have yet tried to develop.
Gene therapy attempts to deliver a piece of DNA into target cells generally by means of a virus capsule, which attaches to the cell’s surface receptors and then uses the cell machinery to make copies of the DNA.
In December 2017, Spark received Food and Drug Administration approval for Luxterna, a gene therapy for a rare form of congenital blindness. The one-time treatment costs $425,000 per eye.
Chicago biotech company AveXis has a gene therapy under review by the FDA to treat spinal muscular atrophy. Also known as floppy baby syndrome, children with the condition are unable to perform even the simplest motor functions. Brian Kaspar, Ph.D., chief scientific officer for the company, showed videos of infants rolling over and sitting up unassisted after a single treatment, and older children running down the hospital hallway or reaching up to press an elevator button.
“These are things that simply put have never seen in spinal muscular atrophy,” Kaspar said. “We got into this business to change the textbooks of this deadly disease.”
AveXis, which has built its own production facility to engineer the viral capsule and the DNA fragments it carries, was purchased by Norvatis for $8.7 billion this week.
It took a little more than two decades to go from the very first clinical trial of gene therapy, a National Institutes of Health study in 1990 for children with a rare form of immunodeficiency disorder, to the first licensed product, Glybera, in 2012.
The pace of development, however, has sharply increased. There are about 700 gene therapy trials listed on clinicaltrials.gov, and the number of investigative new drugs applications for gene therapies received by the FDA has grown dramatically from 22 in 2002 to 106 in 2017, including a 34 percent increase last year.
FDA Commissioner Scott Gottlieb has been a vocal supporter of gene therapy and has directed his staff to help streamline the process to get these treatments to the market.
“We believe that many of these products are going to transform peoples’ lives,” said Wilson Bryan, M.D., director of the FDA’s Office of Tissues and Advanced Therapies.
Despite the progress, many questions remain. There may be a risk that gene therapy, particularly in high doses, has unforeseen complications, and it’s unclear how long the treatments will last.
High said journalists reporting on gene therapy should ensure they wait until studies are published in high quality medical journals to avoid succumbing to the hype that surrounds new treatments.
“Medical journals have become quite skeptical about gene therapy, and so they review these papers extremely rigorously,” High said.
She also addressed the high price tag that comes with gene therapy treatments.
“Our reimbursement system for pharmaceuticals right now is titled towards therapeutics that are given repetitively over a long period of time,” High said. “Gene therapy has the potential … to address in a single one-time administration a long-term need for a new gene.
Spark is working on a gene therapy treatment for hemophilia, for example, which has treatment costs of $250,000 to $400,000 per year for life.
“So in a single intervention, the way our health care system works in the United States, you need to recover the value of this high-value, high-cost therapeutic all at once,” High said. “And that does present some difficulties with the way our payer system is currently set up.”