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SAN FRANCISCO -- Photoreceptor loss in macular telangiectasia (MacTel) type 2 decreased by as much as 56% with a cellular therapy that produces a neurotrophic factor, two sham-controlled trials showed.

The rate of change in elliptical zone (EZ) loss declined by 56.4% in trial A and by 29.2% in trial B with revakinagene taroretcel (NT-501). Retinal sensitivity and reading speed each improved significantly in one of the studies.

Treatment-related serious ocular events were uncommon, including no cases of endophthalmitis or ischemic optic neuropathy, reported Mark Gillies, MD, PhD, of the Save Sight Institute and University of Sydney in Australia, at the American Academy of Ophthalmology meeting.

"In conclusion, we can say that this is the first treatment that has been shown to be safe and effective for MacTel type 2," said Gillies. "It preserved more photoreceptors through 24 months in both studies."

The drug will be submitted to the FDA next year, he noted.

Asked to explain the difference in treatment effects between the two studies, Gillies responded, "Different patient populations, different datasets."

Baseline characteristics were similar in the two studies, including the baseline mean EZ defect. The study with the larger treatment effect did have more patients with a smaller baseline EZ defect, and those patients appeared to benefit more from the treatment.

Historically, MacTel was considered a progressive condition in all patients. Discussion moderator Anita Agarwal, MD, of Sutter Health in San Francisco, said that in her clinical experience, "Some patients maintain 20/30 vision for 20 years. So it doesn't always go bad, but when it does go bad, it stays bad."

"It's true that patients may remain stable for a long period of time and then there's a stepwise drop of five letters or so and then another period of stability," said Gillies. "If you're looking at short periods of time, many patients don't seem to progress, but if you're diagnosed in your 40s, I think those patients do not do well 20 years later."

Patients randomized to the sham intervention had a gradual increase in the area of loss over the 24 months of follow-up, he added.

Two Identically Designed Trials

A bilateral, progressive retinal neurodegenerative disease, leads to central vision loss and functional impairment, associated with of about 0.08 mm² per year. The condition is abnormalities in the Müller glia, retinal pigmented epithelium, and photoreceptors in the central retina. MacTel currently has no approved therapy.

Müller glial cells can protect photoreceptors from cell death by production of neurotrophic factors, including ciliary neurotrophic factor (CNTF). In preclinical models, intravitreal injection of CNTF rescued photoreceptor loss, providing a rationale for clinical investigation.

NT-501 is an encapsulated cell therapy with allogeneic retinal pigment epithelial cells that have a CNTF expression vector. The therapy is surgically implanted into the vitreous cavity, anchored to the sclera, and produces sustained levels of CNTF for as long as 14 years, said Gillies.

The implant was evaluated in two identically designed phase III, sham-controlled trials conducted at 47 sites on three continents (NTMT-03-A and NTMT-03-B). In both trials, patients were randomized to receive the implant or a sham procedure in one study eye.

The primary endpoint was the rate of change in the area of EZ loss from baseline to 24 months. Secondary endpoints included the aggregate sensitivity of the microperimetry of the EZ line break area, monocular reading speed, and quality of life. Safety endpoints included a ≥15-letter loss in best corrected visual acuity (BCVA) at any visit and serious treatment-emergent adverse events (TEAEs).

Key Findings

Baseline characteristics included a mean EZ area loss of about 0.5 mm², mean BCVA of 71-74 letters, mean aggregate sensitivity loss of 49-64 dB, and mean reading speed of 92-96 words per minute. Study participants were primarily white and female, had a mean age of ~60, and a baseline visual acuity of Snellen 20/40.

The results showed a mean difference in rate of EZ area loss of -0.096 mm² in study A (slope 0.074 vs 0.170 mm², P<0.0001) and a mean difference of -0.048 mm² in study B (slope 0.116 vs 0.164 mm², P=0.021). Retinal sensitivity was preserved in study A (25.27 vs 43.02 dB, P=0.0199) but not in study B (30.02 vs 42.98 dB, P=0.7532). Reading speed favored NT-501 in both trials: -6.18 vs -12.20 words in study A (P=0.3849) and -5.46 vs -18.88 words in study B (P=0.0331).

The most common TEAEs associated with NT-501 were mild or moderate delayed dark adaptation and mild or moderate miosis (10% each in study A, 24% and 14% in study B). Suture-related complications accounted for all but one of the serious TEAEs in both NT-501 studies. The one remaining serious TEAE was a case of device extrusion in study B. Five cases of uveitis/iridocyclitis occurred with NT-501 in five patients in study A and none in study B.

A few patients had mild intraocular inflammation in the immediate postoperative period, said Gillies. All cases were attributed to surgery and resolved with topical steroids. One patient had possible retinal vasculitis, identified incidentally as vascular and optic disease leakage in the fellow eye. The condition was monitored and resolved without incident.

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