AAO 2022: Janssen, REGENXBIO, Apellis and More

The American Academy of Ophthalmology 2022 meeting took place in Chicago over the weekend, where industry leaders harnessed the power of gene therapies against wet AMD, geographic atrophy and more.

Janssen’s Gene Therapies Demonstrate Efficacy, Safety

Janssen reported preliminary findings from two of its gene therapy programs, showing good safety profiles and promising signs of efficacy for both.

In the Phase I/II MGT009 study of patients with the inherited retinal disease X-linked retinitis pigmentosa, botaretigene sparoparvovec demonstrated an adverse event profile that was expected and manageable. Most side effects were related to the surgery procedure and not the drug itself. Most toxicities were transient and resolved spontaneously, Janssen reported.

During the study’s dose escalation and expansion phases, botaretigene sparoparvovec resulted in functional improvement in every visual domain assessed, as compared with untreated controls. Pooling the low- and intermediate-dose cohorts also showed better retinal sensitivity after treatment with the gene therapy.

Botaretigene sparoparvovec is being developed and commercialized under a global collaboration between Janssen and MeiraGTx Holdings plc.

Janssen also presented data from a second gene therapy, JNJ-1887. Low, intermediate and high doses of the intravitreal candidate met the primary safety endpoint in a Phase I open-label and dose-escalation study of 17 patients with advanced dry age-related macular generation with geographic atrophy. Lesion growth rates also slowed down following treatment with JNJ-1887, indicating the potential of further evaluation.

Atsena Sees Early Success Against Leber congenital amaurosis

Atsena Therapeutics’ gene therapy candidate ATSN-101 led to clinically meaningful vision improvements in patients with GUCY2D-associated Leber congenital amaurosis (LCA1).

Assessed in a Phase I/II clinical trial, increasing doses of subretinal ATSN-101 led to significantly better retinal sensitivity in 15 LCA1 patients, along with a non-significant but substantial improvement in best-corrected visual acuity, the company reported. There were no serious adverse events associated with the candidate, and most treatment-emergent toxicities were mild and temporary.

A monogenic disease caused by mutations in the GUCY2D gene, LCA1 interferes with normal retina function and can lead to severe vision impairment and even blindness. There is no approved treatment for this disorder and Atsena aims to launch a pivotal trial for ATSN-101.

REGENXBIO/AbbVie Gene Therapy Eases Treatment Burden in Wet AMD

Early data from the Phase II AAVIATE trial revealed treatment with REGENXBIO’s RGX-314, whether through a subretinal or suprachoroidal route, meaningfully reduces the need for anti-VEGF injections in patients with wet age-related macular degeneration, the company reported.

RGX-314 also proved to be safe and effective leading to durable improvements in best-corrected visual acuity and central retinal thickness in treated patients. No serious adverse events were deemed attributable to RGX-314.

Developed in collaboration with AbbVie, RGX-314 is a gene therapy being evaluated as a potential one-time treatment for wet AMD. The candidate is delivered using an AAV8 vector and encodes for an antibody fragment that can target and deactivate the VEGF molecule. RGX-314 is also being studied in diabetic retinopathy with results expected later this year.

Apellis Slows Lesion Growth in Geographical Atrophy in Phase III

Post-hoc analyses of the Phase III OAKS study showed Apellis Pharmaceuticals’ pegcetacoplan can reduce the rate at which the loss of retinal sensitivity occurs in patients with geographical atrophy.

Compared with the sham-control group, patients treated with Apellis’ candidate developed significantly fewer scotomatous points - areas in the retina that have completely lost light sensitivity and function, the company reported. Both beneficial effects increased over time and were significant in patients given pegcetacoplan monthly or every other month.

Pegcetacoplan’s safety profile was consistent with what had already been established in prior studies. Over the 2-year analysis period, new-onset exudations occurred at a rate of 12.2% in patients dosed monthly and 6.7% in those treated every other month. 

The rate of exudation was 3.1% in sham controls. Incidences of infectious endophthalmitis and intraocular inflammation did not differ from other intravitreal therapies.

The marketing authorization for pegcetacoplan is under the FDA’s review and is set to receive a decision in November.