We’re approaching a critical milestone in the fight against blinding retinal diseases, and it has the potential to tremendously boost and accelerate the advancement of virtually all gene therapies in development for dozens of inherited retinal diseases.
Sometime in 2016, Spark Therapeutics will request marketing approval from the U.S. Food and Drug Administration (FDA) for its landmark gene therapy for retinal conditions caused by mutations in the gene RPE65, namely certain forms of Leber congenital amaurosis and retinitis pigmentosa.
The request, formally known as a biologics license application, or BLA, comes on the heels of Spark’s announcement earlier this week that its Phase III trial of the treatment has delivered positive “top-line” results. Among other results, participants, after treatment, significantly improved their ability to navigate a mobility course in dim and bright settings. These individuals, who range in age from 4 to 44, were virtually blind before receiving the therapy.
There are no guarantees that the treatment will be approved, but given the clinical-trial safety and efficacy data reported over the last eight years, we have good reason to be cautiously optimistic. Approval would likely make it the first FDA-approved gene therapy for an eye disease or an inherited condition.
While FDA approval would obviously be great news for people with RPE65 mutations, the regulatory nod is strong affirmation to researchers and biotech companies around the world that gene therapies are a scientifically and commercially viable approach to fighting blindness and possibly other genetic diseases and cancer.
It wasn’t long ago that gene therapy seemed like science fiction. Could we really develop a human-engineered virus to deliver healthy, vision-restoring genes to the retina? Could it be administered through a single retinal injection that would work for several years? Many experts had their doubts, seeing as the approach was so cutting-edge. However, the Foundation Fighting Blindness was compelled to drive gene-therapy research because of its strong potential to save and restore vision for people with inherited retinal conditions. And drive, we did.
While the gene-therapy story began more than 20 years ago, we reached a major turning point in 2001, when the treatment restored vision in blind Briard dogs with LCA, including the overnight media sensation Lancelot. The success in canines opened the door in late 2007 to clinical trials at The Children’s Hospital of Philadelphia and several other institutions, and, today, a thriving biotech is knocking on the door of the FDA for marketing approval.
RPE65 was a strategic disease target for retinal gene therapy development because, technically, it was “low-hanging fruit,” meaning it was easier to treat than other conditions. But with this disease hopefully under our belt soon, we’ll be well-poised to advance gene therapies for a variety of other retinal degenerations, including choroideremia, Usher syndrome, Stargardt disease, retinoschisis, retinitis pigmentosa and achromatopsia. With optogenetics therapies, which are now just moving into clinical trials, we even have the potential to restore vision in someone who is completely blind from a retinal disease, and for whom a genetic cause has not been identified.
Of course, a lot of work remains to develop treatments for the entire spectrum of complex retinal diseases. But FDA approval for the LCA (RPE65) gene therapy would be a giant leap forward in getting vision-saving gene therapies to everyone who urgently needs them.