Intravitreal gene therapy effective, safe in Leber hereditary optic neuropathy
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A significant improvement of visual acuity was reported in eyes treated with a unilateral intravitreal injection of lenadogene nolparvovec for Leber hereditary optic neuropathy, researchers reported at the 2022 American Academy of Neurology annual meeting.
“Leber hereditary optic neuropathy (LHON) is a devastating disease of blindness, typically in young men in the prime of life, in which one eye becomes blind and at the same time, or within a few months, the second eye becomes blind,” Nancy J. Newman, MD, professor of ophthalmology and neurology at Emory Eye Center in Atlanta, said during an AAN press conference prior to the meeting.
Expanding on previous gene therapy trials, Newman and colleagues conducted a phase 3 trial and enrolled 98 participants with LHON who had experienced vision loss for at least 12 months. Each participant received a unilateral intravitreal injection of lenadogene nolparvovec in their first-affected eye and either gene therapy or placebo in their second eye. Forty-eight participants received bilateral treatment, and 50 were treated unilaterally.
“In prior studies, we have shown that one can take gene therapy with a viral vector and inject a complement of the abnormal gene into the eye, where, hopefully, it is taken up by the retinal ganglion cells and makes up for the abnormality,” Newman said.
At a 1.5-year follow-up, the difference in best-corrected visual acuity improvement between second-affected eyes was equivalent to 3 ETDRS letters in favor of lenadogene nolparvovec, researchers reported.
From nadir, the treated eyes increased by 19 ETDRS letters in the first eye and 16 in the second (P < .0001). Comparably, those who received placebo increased by 13 ETDRS (P < .0001).
Further, no severe adverse events were reported, although those treated with the drug had more ocular inflammation, which is to be expected, Newman said.
“All second-effected eyes, whether they received an injection of the drug or an injection of placebo, did improve,” she concluded. “And they improved more again than what would be expected from the natural history of the disease.”