KOLOA, Hawaii —Voretigene neparvovec benefits patients with Leber congenital amaurosis and may help advance future gene therapies, according to a speaker at Retina 2020.
“The premise of gene therapy is to deliver a normal copy of the gene ... allowing that cell to produce the protein, which it could not produce at that point. What that means is that it is ideally performed prior to significant cell loss,” Aaron Nagiel, MD, PhD, said.
Gene therapy is very effective for autosomal and X-linked recessive conditions, he said.
“I think that we as retina specialists have come to the forefront of gene therapy because subretinal delivery is so powerful in that we can deliver a dose in the exact location in contact with those cells as needed with less systemic exposure or possibly no systemic exposure and less inflammation,” he said.
Voretigene neparvovec was the first FDA approved gene therapy for inherited retinal dystrophy, including Leber congenital amaurosis, according to Nagiel.
To deliver the drug surgically in patients with Leber congenital amaurosis, Nagiel prepares two 0.8 cc syringes — one for use and one for backup. The drug must be used within 4 hours, he emphasized. He uses the MedOne Microdose kit because it allows full surgical control of delivery. He uses intraoperative OCT to confirm subretinal delivery in real time.
Over the course of almost 2 years, Nagiel and his team has noticed good follow-up in most patients.
“The visual acuities don’t budge much ... most stay about the same even though they report significant improvements in their visual function [in the real world]. So, there’s kind of a disconnect there. ... We don’t know why that is,” Nagiel said.
Light sensitivity improves and visual fields improve significantly with voretigene neparvovec treatment, he said.
Some complications with voretigene neparvovec treatment include vitreous opacities, decreased central VA and perifoveal chorioretinal atrophy. But, overall, there were no major safety issues, according to Nagiel.
“Molecular diagnosis is a driving force behind gene therapy,” Nagiel said. “We really need to get these patients identified early and that means genetic testing.”
“Voretigene neparvovec will pave the way for future gene therapy, new trials and other treatments,” he added. – by Alaina Tedesco
Reference: Nagiel A. Gene therapy for Leber congenital amaurosis: The CHLA experience. Presented at: Retina 2020; Jan. 19-24, 2020; Koloa, Hawaii.
Disclosure: Nagiel reports being a consultant for REGENXBIO.