Is Revakinagene Taroretcel-lwey (Encelto) implant medically necessary for the treatment of adult members with idiopathic macular telangiectasia type 2 (MacTel)?

Medical Necessity Determination for Revakinagene Taroretcel-lwey (Encelto) in Idiopathic Macular Telangiectasia Type 2

Revakinagene taroretcel-lwey (Encelto) is medically necessary for a one-time intravitreal implantation per affected eye when all four Aetna CPB criteria (A through D) are met, as this represents the only FDA-approved treatment for MacTel type 2 that has demonstrated statistically significant reduction in photoreceptor loss and slowing of retinal degeneration in phase 3 trials. 1, 2

FDA Approval and Indication

• Revakinagene taroretcel received FDA approval in March 2025 as the first approved treatment for idiopathic macular telangiectasia type 2 in adults 1
• The therapy consists of an encapsulated cell-based gene therapy containing 200,000-440,000 allogeneic retinal pigment epithelial cells expressing recombinant human ciliary neurotrophic factor 1
• This represents a breakthrough for a disease that previously had no evidence-based treatment for the nonproliferative stage 3

Evidence Supporting Medical Necessity

The phase 3 clinical trial data (NTMT-03-A and NTMT-03-B) demonstrated statistically significant slowing of ellipsoid zone area loss, which directly addresses the progressive photoreceptor degeneration that defines MacTel type 2 disease progression. 2

Primary Efficacy Outcomes:

• In NTMT-03-A: EZA loss rate was 0.075 mm²/24 months with NT-501 versus 0.166 mm²/24 months with sham (difference -0.091 mm²/24 months, 95% CI -0.125 to -0.056, P<0.001) 2
• In NTMT-03-B: EZA loss rate was 0.111 mm²/24 months with NT-501 versus 0.160 mm²/24 months with sham (difference -0.049 mm²/24 months, 95% CI -0.089 to -0.008, P=0.02) 2
• Both trials showed consistent benefit in slowing photoreceptor loss, which is the primary pathologic mechanism causing vision loss in MacTel type 2 2

Natural History Without Treatment:

• MacTel type 2 is a chronic, slowly progressive bilateral neurodegenerative macular disease that leads to retinal atrophy and visual impairment over decades 4, 5
• Without treatment, visual acuity decreases on average 1.2 lines by 3 years, 2 lines by 5 years, and 4.1 lines by 10 years 5
• The disease manifests during the fourth to sixth decades of life and causes progressive foveal atrophy with no previously available disease-modifying treatment 4, 3

Rationale for CPB Criteria Alignment

Criterion A (Diagnostic Confirmation):

The requirement for fluorescein leakage plus specific morphologic features ensures accurate diagnosis of MacTel type 2, which is essential because the phase 3 trials enrolled only confirmed MacTel type 2 patients. 2

• Fluorescein angiography showing deep intraretinal hyperfluorescent leakage in the temporal parafoveal area is a characteristic diagnostic finding 4
• The specified features (hyperpigmentation outside 500 micron radius, retinal opacification, crystalline deposits, right-angle vessels, inner/outer lamellar cavities) represent established diagnostic criteria for MacTel type 2 4, 3

Criterion B (EZA Break Size 0.16-2.00 mm²):

This criterion directly corresponds to the inclusion criteria used in the pivotal phase 3 trials that demonstrated efficacy, ensuring treatment is provided to patients most likely to benefit. 2

• The ellipsoid zone break represents photoreceptor inner segment/outer segment junction loss, which is the primary outcome measure in the clinical trials 2
• Patients with EZA within this range demonstrated measurable benefit from treatment in both phase 3 trials 2
• This range excludes patients with either minimal disease (unlikely to progress rapidly) or advanced disease (beyond the therapeutic window studied in trials)

Criterion C (BCVA 54-Letter Score or Better):

The visual acuity threshold of 20/80 or better ensures patients retain sufficient visual function to benefit from slowing disease progression, as patients with more severe vision loss were not studied in the pivotal trials. 2

• The phase 3 trials enrolled patients with measurable visual function who could demonstrate benefit from slowing photoreceptor loss 2
• MacTel type 2 patients with better baseline visual acuity have better long-term outcomes, and visual preservation correlates with mainly extrafoveal disease manifestation 5

Criterion D (Adequate Fixation and Media Clarity):

This criterion ensures the ability to perform necessary diagnostic imaging (SD-OCT) to confirm diagnosis, measure baseline EZA, and monitor treatment response. 2

• Spectral domain optical coherence tomography is essential for measuring ellipsoid zone area, which is the primary efficacy endpoint 2
• Clear ocular media and steady fixation are required for accurate OCT imaging to assess treatment eligibility and monitor outcomes 4

Safety Profile Supporting Medical Necessity

• Treatment-emergent serious adverse events did not differ between NT-501 and sham groups in phase 3 trials 2
• BCVA loss of 15 or more letters did not differ between treatment groups 2
• Miosis occurred in 17% and 14% of NT-501 recipients in the two trials (versus 0% in sham groups) 2
• Delayed dark adaptation occurred in 17% and 24% of NT-501 recipients (versus 0-2% in sham groups) 2
• The favorable risk-benefit profile supports medical necessity when criteria are met, as the treatment slows disease progression with manageable adverse effects 2

One-Time Administration Rationale

The one-time intravitreal implantation per affected eye is appropriate because the encapsulated cell therapy is designed to provide sustained ciliary neurotrophic factor production over an extended period, as demonstrated by the 24-month efficacy data from phase 3 trials. 1, 2

• The implant contains viable allogeneic RPE cells that continuously produce rhCNTF 1
• The phase 3 trials demonstrated sustained benefit over 24 months following a single implantation 2
• This represents a fundamentally different treatment paradigm compared to repeated intravitreal injections required for anti-VEGF therapy 3

Clinical Context and Limitations

It is critical to understand that revakinagene taroretcel addresses the nonproliferative stage of MacTel type 2 by slowing photoreceptor degeneration, not the neovascular complications that may develop in some patients. 4, 3

• Approximately 10-20% of MacTel type 2 patients develop subretinal neovascularization (proliferative stage) 4
• Patients who develop neovascular membranes may benefit from intravitreal anti-VEGF therapy for the neovascular component 3
• The CPB criteria appropriately focus on nonproliferative disease, which represents the majority of MacTel type 2 patients and the population studied in phase 3 trials 2

Conclusion on Medical Necessity

When all four CPB criteria (A through D) are met, revakinagene taroretcel-lwey represents a medically necessary intervention because it is the only FDA-approved treatment that addresses the underlying neurodegenerative process in MacTel type 2, with level 1 evidence demonstrating statistically significant slowing of photoreceptor loss and a favorable safety profile. 1, 2

The criteria ensure appropriate patient selection based on the phase 3 trial inclusion criteria, maximizing the likelihood of benefit while minimizing treatment of patients outside the studied population. The one-time administration per affected eye is consistent with the sustained-release mechanism of the encapsulated cell therapy and the 24-month efficacy data from pivotal trials. 1, 2