Neuroprotectant Treatment for MacTel Type 2

Sustained intraocular delivery of ciliary neurotrophic factor (CNTF) using NT-501 encapsulated cell therapy (revakinagene taroretcel) is safe and effective for treating macular telangiectasia (MacTel) type 2, suggest the results of two phase 3 clinical trials.

The NT-501 implant is inserted into the vitreous and sutured to the sclera. Reviewing the outcomes of the two phase 3 studies, Emily Y Chew MD reported both investigations met their primary endpoint, showing significantly greater photoreceptor preservation after 2 years in eyes receiving the first-in-class therapy compared to control eyes that underwent a sham operation. Analyses of secondary efficacy measures showed preserved retinal sensitivity within the ellipsoid zone break line in participants receiving NT-501, but the treatment effect was not statistically significant in either study.

“MacTel type 2 was the first disease to demonstrate benefit from treatment with NT-501, partly because of the availability of a good outcome measure for quantifying the structural change that occurs with disease progression,” Dr Chew said. “We believe that results of a pooled analysis of retinal sensitivity data may show a significant difference favouring NT-501 versus sham therapy.”

The two phase 3 trials involved more than 200 participants enrolled at 47 international sites. Patients aged 21 to 80 were eligible if they had a MacTel type 2 diagnosis, an ellipsoid zone break in the study eye and en face ellipsoid zone between 0.16 and 2.00 mm², and BCVA ≥54 ETDRS letters (Snellen equivalent ≥20/80).

The study participants were primarily white and female, with a mean age of about 60 years and a baseline BCVA of about 20/40.

Data on change in ellipsoid zone area from baseline to 24 months showed that compared to sham, NT-501 reduced the loss rate by 55% in one study and 31% in the second.

“The treatment effect was statistically significant in both studies,” Dr Chew said. “Reasons for the difference between studies in magnitude of the effect might be related to differences in the participants’ baseline lesion size and other patient characteristics.”

Microperimetry measured the retinal sensitivity, and Dr Chew suggested that differences between the two studies in lesion size and the quality of microperimetry data might explain why only one study demonstrated the benefit of better retinal sensitivity preservation.

“We don’t know for sure why the retinal sensitivity results varied, but it is well known that microperimetry testing can be very difficult for patients,” she said.

“We will be looking at various factors and hopefully doing an extension study to continue following patients. Examination of explanted NT-501 implants shows CNTF release remains durable for at least 14 years.”

Dr Chew described the safety profile of NT-501 as “excellent,” adding it was very well tolerated. Ocular treatment-emergent adverse events were uncommon and mostly mild and transient. There were a few serious ocular treatment-emergent adverse events, but most were related to surgery and, therefore, expected.

There were no serious treatment-emergent adverse events of endophthalmitis or ischemic optic neuropathy nor any instances of clinically significant intraocular inflammation.

“The rates of delayed dark adaptation and miosis were higher in the NT-501 groups compared to sham, but even some sham patients had delayed dark adaptation,” Dr Chew said.

Dr Chew presented the results at AAO 2024 in Chicago, US.

Emily Y Chew MD is Director of the Division of Epidemiology and Clinical Applications at the National Eye Institute/National Institutes of Health, Bethesda, Maryland, US. echew@nei.nih.gov