Lenadogene nolparvovec safe in patients with Leber hereditary optic neuropathy

Lenadogene nolparvovec is well tolerated among patients with Leber hereditary optic neuropathy, being associated with mostly mild ocular side effects that can be resolved with conventional ophthalmologic treatments, according to the results of the LHON study.

LHON pooled safety data from five clinical studies, which involved a total of 189 patients. These patients received either single unilateral or bilateral intravitreal injections of a recombinant adeno-associated virus 2 (rAAV2/2) vector encoding the human wild-type ND4 gene.

Researchers collected up to 5 years’ worth of adverse events (AEs) data throughout the studies. They looked at intraocular inflammation and increased intraocular pressure (IOP) as ocular AEs of special interest. They also evaluated ocular examinations, vector bio-dissemination, and systemic immune responses against rAAV2/2.

The majority of patients (95.2 percent) received 9 × 1010 viral genomes, and 87.8 percent had at least 2 years of follow-up. At least one systemic AE occurred in 75.1 percent of patients, but systemic treatment-related AEs occurred in three patients, none of which were serious.

Meanwhile, intraocular inflammation developed in 75.6 percent of lenadogene nolparvovec-treated eyes. Nearly all cases of intraocular inflammation occurred in the anterior chamber (58.8 percent) or in the vitreous (40.3 percent); 90.3 percent was of mild and 8.8 percent was of moderate intensity. Most of these AEs responded to topical corticosteroids alone. All IOP increases were mild to moderate in intensity.

None of the AEs led to treatment discontinuation. Meanwhile, bio-dissemination of lenadogene nolparvovec and systemic immune response were limited. The safety profile was similar between patients treated bilaterally and unilaterally.

The findings show that lenadogene nolparvovec has good overall safety profile with excellent systemic tolerability, consistent with limited bio-dissemination.