Revakinagene Taroretcel-lwey (Encelto)

Number: 1079

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

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Policy

Scope of Policy

This Clinical Policy Bulletin addresses revakinagene taroretcel-lwey (Encelto) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

Note: Requires Precertification: 

Precertification of revakinagene taroretcel-lwey (Encelto) is required of all Aetna participating providers and members in applicable plan designs. For precertification of revakinagene taroretcel-lwey (Encelto), contact National Medical Excellence (NME) at 877-212-8811.

Note: Unless member's health plan has elected not to require, gene and cellular therapies must be administered at an Aetna Institutes® Gene Based, Cellular and Other Innovative Therapy (GCIT®) Network. For revakinagene taroretcel-lwey (Encelto), see Aetna Institutes® GCIT Designated Centers. 

1. Exclusions 

   Aetna considers members with any of the following exclusions not eligible for Encelto implant:

   1. Member has evidence of intraretinal neovascularization or subretinal neovascularization (SRNV) (e.g., neovascular MacTel), as evidenced by hemorrhage, hard exudate, subretinal fluid or intraretinal fluid in either eye;
   2. Member has received intravitreal steroid therapy for non-neovascular MacTel within the past 3 months;
   3. Member has previously received intravitreal anti-vascular endothelial growth factor (VEGF) therapy in the affected eye(s) or has received intravitreal anti-VEGF in the non-affected eye within the past 3 months;
   4. Member has evidence of central serous chorio-retinopathy in either eye;
   5. Member has evidence of pathologic myopia in either eye;
   6. Member has significant corneal or media opacities in either eye;
   7. Member has had a vitrectomy, penetrating keratoplasty, trabeculectomy, or trabeculoplasty;
   8. Member has any of the following lens opacities:
      
      
      1. Cortical opacity greater than standard 3; or
      2. Posterior subcapsular opacity greater than standard 2; or
      3. A nuclear opacity greater than standard 3 as measured on the Age-Related Eye Disease Study (AREDS) clinical lens grading system;
   9. Member has undergone lens removal in the previous 3 months or YAG laser within 4 weeks;
   10. Member has evidence of intraretinal hyperreflectivity by optical coherence tomography (OCT);
   11. Member is on chemotherapy;
   12. Member with a history of ocular herpes virus in either eye;
   13. Member has an ocular or periocular infection;
   14. Member has a known hypersensitivity to Endothelial Serum Free Media (Endo-SFM);
   15. Member has any of the following comorbidities:
       
       
       1. Glaucoma;
       2. Severe nonproliferative or proliferative diabetic retinopathy; or
       3. Uveitis;
   16. Member must be able to temporarily discontinue antithrombotic therapy (e.g., oral anticoagulants, aspirin, nonsteroidal anti-inflammatory drugs) prior to insertion surgery to reduce the risk of implantation related vitreous hemorrhage;
   17. Member has not received a previous treatment course of Encelto in the affected eye(s).

2. Prescriber Specialties

   This medication must be prescribed by an ophthalmologist.

3. Criteria for Initial Approval

   Idiopathic Macular Telangiectasia Type 2 (MacTel)

   Aetna considers revakinagene taroretcel-lwey (Encelto) implant medically necessary for a one time intravitreal implantation per affected eye(s) for the treatment of adult members with idiopathic macular telangiectasia type 2 (MacTel) when all of the following criteria are met:

   1. Member must have at least one eye positive for the diagnosis of idiopathic macular telangiectasia type 2 (MacTel) as evidenced by fluorescein leakage and at least one of the following features: 

      1. Hyperpigmentation that is outside of a 500 micron radius from the center of the fovea; 
      2. Retinal opacification;
      3. Crystalline deposits;
      4. Right-angle vessels; or
      5. Inner/outer lamellar cavities; and
   2. Member must have a photoreceptor inner segment/outer segment (IS/OS PR) break (loss) in ellipsoid zone (EZ) (area of IS/OS loss) between 0.16 mm² and 2.00 mm² measured by spectral domain-optical coherence tomography (SD-OCT) ; and
   3. Member has a best corrected visual acuity (BCVA) of 54-letter score or better (20/80 or better) as measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at screening; and
   4. Member must have steady fixation and sufficiently clear ocular media for good quality photographs.

   Note: Aetna considers removal of Encelto implant medically necessary, if vitrectomy with a complete gas fill or silicone oil fill is required or infectious endophthalmitis occurs.

   Aetna considers all other indications as experimental, investigational, or unproven.

4. Related Policies 

   1. CPB 0393 - Vitrectomy

Dosage and Administration

Revakinagene taroretcel-lwey is supplied as Encelto implant with one single-dose implant containing 200,000 to 440,000 allogeneic retinal pigment epithelial cells expressing recombinant human ciliary neurotropic factor (rhCNTF) for intravitreal implantation only.

• Encelto is intended for surgical intravitreal implantation under aseptic conditions by a qualified ophthalmologist.
• The recommended dose is one Encelto implant per affected eye containing 200,000 to 440,000 allogeneic retinal pigment epithelial cells expressing rhCNTF.
• Encelto should be carefully inspected prior to use and refer to the instructions for use when preparing for and performing surgical placement or removal of Encelto.

Source: Neurotech Pharmaceuticals, 2025a

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Other CPT codes related to the CPB:
65730	Keratoplasty (corneal transplant); penetrating (except in aphakia or pseudophakia)
65750	Keratoplasty (corneal transplant); penetrating (in aphakia)
65755	Keratoplasty (corneal transplant); penetrating (in pseudophakia)
65855	Trabeculoplasty by laser surgery
66170	Fistulization of sclera for glaucoma; trabeculectomy ab externo in absence of previous surgery
66172	Fistulization of sclera for glaucoma; trabeculectomy ab externo with scarring from previous ocular surgery or trauma (includes injection of antifibrotic agents)
66821	Discission of secondary membranous cataract (opacified posterior lens capsule and/or anterior hyaloid); laser surgery (eg, YAG laser) (1 or more stages)
67027	Implantation of intravitreal drug delivery system (eg, ganciclovir implant), includes concomitant removal of vitreous
67028	Intravitreal injection of a pharmacologic agent (separate procedure)
67036 – 67043	Vitrectomy, mechanical, pars plana approach
HCPCS codes covered if selection criteria are met:
Revakinagene taroretcel-lwey (Encelto) – no specific code
Other HCPCS codes related to the CPB:
J1095	Injection, dexamethasone 9 percent, intraocular, 1 microgram
J1096	Dexamethasone, lacrimal ophthalmic insert, 0.1 mg
J0178	Injection, aflibercept, 1 mg
J2778	Injection, ranibizumab, 0.1 mg
J2779	Injection, ranibizumab, via intravitreal implant (susvimo), 0.1 mg
J7311	Injection, fluocinolone acetonide, intravitreal implant (retisert), 0.01 mg
J7312	Injection, dexamethasone, intravitreal implant, 0.1 mg
J7313	Injection, fluocinolone acetonide, intravitreal implant (iluvien), 0.01 mg
J7314	Injection, fluocinolone acetonide, intravitreal implant (Yutiq), 0.01 mg
J8501 – J9999	Chemotherapy drugs
ICD-10 codes covered if selection criteria are met:
H35.071 – H35.079	Retinal telangiectasis [macular type 2 (MacTel)]
ICD-10 codes not covered for indications listed in the CPB:
B00.50 – B00.59	Herpesviral ocular disease
E10.3211 – E10.3499	Type 1 diabetes mellitus with mild, moderate, severe nonproliferative diabetic retinopathy
E10.3511 – E10.3599	Type 1 diabetes mellitus with proliferative diabetic retinopathy
E11.3211 – E11.3499	Type 2 diabetes mellitus with mild, moderate, severe nonproliferative diabetic retinopathy
E11.3511 – E11.3599	Type 1 diabetes mellitus with proliferative diabetic retinopathy
H17.10 – H17.13	Central corneal opacity
H17.811 – H17.89	Other corneal scars and opacities
H20.00 – H20.9	Iridocyclitis
H25.011 – H25.099	Age-related incipient cataract
H25.10 – H25.13	Age-related nuclear cataract
H26.40 – H26.499	Secondary cataract
H35.051 – H35.059	Retinal neovascularization, unspecified
H35.711 – H35.719	Central serous chorioretinopathy
H40.001 – H42	Glaucoma
H43.391 – H43.399	Other vitreous opacities
H44.111 – H44.19	Panuveitis
H44.131 – H44.139	Sympathetic uveitis
H44.20 – H44.2E9	Degenerative myopia [pathologic]

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Background

U.S. Food and Drug Administration (FDA)-Approved Indications 

• Encelto is indicated for the treatment of adults with idiopathic macular telangiectasia type 2 (MacTel).

Revakinagene taroretcel-lwey is available as Encelto (Neurotech Pharmaceuticals, Inc.), an allogeneic encapsulated cell-based gene therapy that contains 200,000 to 440,000 allogeneic retinal pigment epithelial cells expressing recombinant human ciliary neurotropic factor (rhCNTF) (NTC-201-6A cell line) for surgical intravitreal placement. Encelto is made up of an opaque, semi-permeable white to off-white capsule surrounding a scaffold of polyethylene terephthalate (PET) yarn, loaded with rhCNTF secreting allogenic retinal pigment epithelial cells (NTC-201-6A cell line). Each end of the semi-permeable capsule is sealed with medical grade methacrylate adhesive, and to one end a titanium fixation loop is attached. Encelto width is 1.2 ± 0.1 mm, length is 6.1 ± 0.4 mm, and its internal diameter is 0.88 ± 0.02 mm (Neurotech Pharmaceuticals, 2025a).

Encelto secrets recombinant human capillary neurotrophic factor (rhCNTF), which is one of numerous neurotrophic factors endogenously produced by neurons and supporting glial cells. Exogenous CNTF is proposed to initially target Müller glia to initiate a cascade of signaling events that may promote survival. Encelto's mechanism of action is not fully understood (Neurotech Pharmaceuticals, 2025a).

According to the prescribing information, Encelto carries the following contraindications, warnings and precautions, and adverse reactions:

• Contraindications:

  • Ocular or periocular infections.
  • Known hypersensitivity to endothelial serum free media (Endo-SFM).
    
    

• Warnings and precautions:

  • Encelto implantation has been associated with severe vision loss, infectious endophthalmitis, retinal tears and/or detachment, vitreous hemorrhage, implant extrusion, cataract formation, suture related complications, and delayed dark adaptation. Patients should be instructed to report signs or symptoms that could be associated with these events without delay. Additional surgical and/or medical management may be required.
  • Vitreous hemorrhage: Temporarily discontinue antithrombotic medication prior to Encelto insertion surgery to reduce the risk of implantation related vitreous hemorrhage. Vitreous hemorrhages occurring greater than one year from implantation could be a sign of Encelto extrusion. The surgical site should be examined closely and the Encelto should be surgically repositioned if indicated.
    
    

• Adverse reactions:

  • The most common adverse reactions (incidence ≥2%) were conjunctival hemorrhage, delayed dark adaptation, foreign body sensation, eye pain, suture related complications, miosis, conjunctival hyperemia, eye pruritus, ocular discomfort, vitreous hemorrhage, blurred vision, headache, dry eye, eye irritation, cataract progression or formation, vitreous floaters, severe vision loss, eye discharge, anterior chamber cell, iridocyclitis.

On March 5, 2025, the U.S. Food and Drug Administration (FDA) approved revakinagene taroretcel-lwey (Encelto) for the treatment of macular telangiectasia type 2 (MacTel). The FDA approval was based on supporting data from two phase 3 studies (Neurotech Pharmaceuticals, 2025b).

Investigators evaluated the efficacy of revakinagene taroretcel-lwey (Encelto) was evaluated in two studies, Study NTMT-03-A (Study 1) and Study NTMT-03-B (Study 2).

Study 1 was a randomized, multi-center, sham-controlled, phase 3 study which enrolled adults with MacTel. The patients were required to have a photoreceptor inner segment/outer segment (IS/OS PR) break (loss) in ellipsoid zone (EZ) between 0.16 and 2.00 mm² measured by spectral domain-optical coherence tomography (SD-OCT) and best corrected visual acuity (BCVA) of 54-lettter score of better (20/80 or better) as measured by the Early Treatment Diabetic Retinopathy Study (EDTRS) chart at screening. Patients with neovascular Mac Tel were excluded (Neurotech Pharmaceuticals, 2025a).

Patients were randomized to receive either Encelto intravitreal implant or sham procedure under standard operative procedures. In the Encelto group, patients underwent conjunctival peritomy, implant placement in the vitreous cavity via sclerotomy and closure with sutures. In the Sham group, patients underwent conjunctival peritomy, scleral pressure, and conjunctival closure with sutures. One hundred and fifteen (Encelto group: 58; Sham group: 57) of 120 patients underwent the assigned procedure and were included in the analysis of efficacy (Neurotech Pharmaceuticals, 2025a).

The median (min, max) baseline EZ area was 0.35 (0.15, 1.99) mm² for the Encelto group and 0.36 (0.16, 1.7) mm² for the Sham group. The median (min, max) baseline aggregate sensitivity of microperimetry within the EZ break area 35.2 (0.75, 398.8) dB for the Encelto group and 35.5 (2, 281.3) dB for the Sham group (Neurotech Pharmaceuticals, 2025a).

The primary efficacy outcome measure was the rate of change in the area of EZ loss (IS/OS, macular PR loss) over 24 months, as measured by SD-OCT. The secondary outcome measure was the mean change in aggregate sensitivity loss microperimetry within the EZ break area from baseline to Month 24. The rate of change in EZ area loss from baseline over 24 months was statistically significant (95% Confidence Interval [CI]; p<0.0001) for the Encelto group; 0.075 mm² (0.05, 0.10) versus the Sham group; 0.166 mm² (0.14, 0.19) (Neurotech Pharmaceuticals, 2025a). 

Study 2 was a randomized, multi-center, sham-controlled, phase 3 study which enrolled adults with MacTel. The patients were required to have an IS/OS PR break in EZ between 0.16 and 2.00 mm² measured by SD-OCT and BCVA of 54-letter score or better (20/80 or better) as measured by the ETDRS chart at screening. Patients with neovascular MacTel were excluded (Neurotech Pharmaceuticals, 2025a).

Patients were randomized to receive either Encelto intravitreal implant or sham procedure under standard operative procedures. In the Encelto group, patients underwent conjunctival peritomy, implant placement in the vitreous cavity via sclerotomy and closure with sutures. In the Sham group, patients underwent conjunctival peritomy, scleral pressure, and conjunctival closure with sutures. One hundred and thirteen (Encelto group: 59; Sham group: 54) comprised the efficacy analysis population (Neurotech Pharmaceuticals, 2025a). 

The median (min, max) baseline aggregate sensitivity of microperimetry within the 450 EZ break area 40.07 (4.82, 291.52) dB for the Encelto group and 28.86 (0.33, 221.17) dB for the 451 Sham group (Neurotech Pharmaceuticals, 2025a).

The primary efficacy outcome measure was the rate of change in the area of EZ loss (IS/OS, macular PR loss) over 24 months, as measured by SD-OCT. The secondary outcome measure was the mean change in aggregate sensitivity loss microperimetry within the EZ break area from baseline to Month 24. The rate of change in EZ area loss from baseline over 24 months was statistically significant (95% CI; p=0.0186) for the Encelto group; 0.111 mm² (0.08, 0.14) versus the Sham group; 0.160 mm² (0.13, 0.19) (Neurotech Pharmaceuticals, 2025a).

The two phase 3 studies demonstrated that, after placement of the implant, Encelto significantly slowed the loss of macular photoreceptors in MacTel patients over 24 months (Neurotech Pharmaceuticals, 2025b).

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References