Lunsotogene Parvec-cwha (Otarmeni)

Number: 1103

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 lunsotogene parvec-cwha (Otarmeni) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

Otarmeni has been identified as an Aetna Gene-based, Cellular & Other Innovative Therapies (GCIT®) product that receives dedicated review by the Aetna GCIT team for Commercial lines of business. 

Note: Requires Precertification: 

Precertification of lunsotogene parvec-cwha (Otarmeni) is required of all Aetna participating providers and members in applicable plan designs. For precertification of lunsotogene parvec-cwha (Otarmeni), call (866) 752-7021 or fax (888) 267-3277. For Statement of Medical Necessity (SMN) precertification forms, see Specialty Pharmacy Precertification. 

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 lunsotogene parvec-cwha (Otarmeni), see Aetna Institutes® GCIT Designated Networks. 

1. Prescriber Specialties

   This medication must be prescribed by a surgeon experienced in intracochlear surgery and trained in the administration procedure.

2. Criteria for Initial Approval

   Aetna considers a one dose total per ear of lunsotogene parvec-cwha (Otarmeni) medically necessary for the treatment of OTOF-related hearing loss when all of the following criteria are met:

   1. Member is 17 years of age or younger; and
   2. Presence of biallelic, likely pathogenic or pathogenic OTOF variants; and
   3. Member has profound sensorineural hearing loss (SNHL; greater than or equal to 90 dB HL) based on behavioral and physiologic measurements (auditory brainstem response [ABR]) of inner ear function; and
   4. Outer hair cell presence is confirmed by either of the following:
      
      
      1. Presence of otoacoustic emissions (greater than or equal to 6 dB signal-to-noise ratio) at greater than or equal to 3 frequencies from 1 to 8 kHz in the ear(s) to be injected; or
      2. Presence of cochlear microphonics in the ear(s) to be injected; and
   5. Member has no evidence from measures of hearing loss that show a dependence on body temperature; and
   6. Member does not have surgical anatomy that would preclude or meaningfully impact the planned surgical approach (e.g., abnormal mastoid pneumatization, enlarged cochlear or vestibular aqueduct) as indicated by medical imaging (e.g., computed tomography [CT] or magnetic resonance imaging [MRI]) in the ear(s) to be injected; and
   7. Member does not have a history or presence of the following:
      
      
      1. Other permanent or untreatable hearing loss conditions
      2. Cochlear implants in the ear(s) to be injected
      3. Malignancies
      4. Meningitis; and

   8. Member has not received Otarmeni in the same ear or any other gene therapy previously.

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

3. Intraoperative Neurophysiological Monitoring

   Aetna considers monitoring the facial nerve using intraoperative facial nerve-monitoring (IFNM) medically necessary throughout the Otarmeni procedure.

4. Related Policies 

   1. CPB 0034 - Aural Rehabilitation
   2. CPB 0140 - Genetic Testing
   3. CPB 0181 - Evoked Potential Studies
   4. CPB 0564 - Electrocochleogram and Perilymphatic Pressure Measurement
   5. CPB 0697 - Intraoperative Neurophysiological Monitoring

Dosage and Administration

Below includes dosing recommendations per FDA-approved prescribing information.

Otarmeni is supplied as sterile suspension of lunsotogene parvec-cwha for intracochlear infusion. Each single-dose vial contains a nominal titer of 3.0 × 10¹³ vector genomes per milliliter (vg/mL) of Otarmeni and has an extractable volume of 0.63 mL.

The recommended dose of Otarmeni for each ear is 7.2 × 10¹² (vg) in a total volume of 0.24 mL, administered by a single-dose intracochlear infusion, using the provided administration kit.

Otarmeni is administered in a surgical suite under general anesthesia with controlled aseptic conditions by a surgeon experienced in intracochlear surgery and trained in the Otarmeni administration procedure. Per the Full Prescribing Information, consider monitoring the facial nerve using intraoperative facial nerve-monitoring (IFNM) throughout the procedure.

Source: Regeneron Pharmaceuticals, 2026

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Other CPT codes related to the CPB:
Intracochlear infusion -no specific codes
70480	Computed tomography, orbit, sella, or posterior fossa or outer, middle, or inner ear; without contrast material
70481	with contrast material(s)
70482	without contrast material, followed by contrast material(s) and further sections
70551	Magnetic resonance (eg, proton) imaging, brain (including brain stem); without contrast material
70552	with contrast material(s)
70553	without contrast material, followed by contrast material(s) and further sequences
92558	Evoked otoacoustic emissions, screening (qualitative measurement of distortion product or transient evoked otoacoustic emissions), automated analysis
92587	Distortion product evoked otoacoustic emissions; limited evaluation (to confirm the presence or absence of hearing disorder, 3-6 frequencies) or transient evoked otoacoustic emissions, with interpretation and report
92588	comprehensive diagnostic evaluation (quantitative analysis of outer hair cell function by cochlear mapping, minimum of 12 frequencies), with interpretation and report
92650	Auditory evoked potentials; screening of auditory potential with broadband stimuli, automated analysis
92651	for hearing status determination, broadband stimuli, with interpretation and report
92652	for threshold estimation at multiple frequencies, with interpretation and report
92653	neurodiagnostic, with interpretation and report
95940	Continuous intraoperative neurophysiology monitoring in the operating room, one on one monitoring requiring personal attendance, each 15 minutes (List separately in addition to code for primary procedure)
95941	Continuous intraoperative neurophysiology monitoring, from outside the operating room (remote or nearby) or for monitoring of more than one case while in the operating room, per hour (List separately in addition to code for primary procedure)
HCPCS codes covered if selection criteria are met:
Lunsotogene parvec-cwha (Otarmeni)- No specific codes
Other HCPCS codes related to the CPB:
G0453	Continuous intraoperative neurophysiology monitoring, from outside the operating room (remote or nearby), per patient, (attention directed exclusively to one patient) each 15 minutes (list in addition to primary procedure)
ICD-10 code covered if selection criteria are met:
H91.8X1 - H91.8X9	Other specified hearing loss [OTOF-related hearing loss]
ICD-10 codes not covered for indications listed in the CPB:
C30.1	Malignant neoplasm of middle ear
C43.20 – C43.22	Malignant melanoma of ear and external auricular canal
C44.201 – C44.299	Other and unspecified malignant neoplasm of skin of ear and external auricular canal
G00.0 – G03.9	Meningitis

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Background

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

• Otarmeni is an adeno-associated virus vector-based gene therapy indicated for the treatment of pediatric and adult patients with severe-to-profound and profound sensorineural hearing loss (any frequency greater than 90 dB HL) associated with molecularly confirmed biallelic variants in the OTOF gene, preserved outer hair cell function, and no prior cochlear implant in the same ear. 

  This indication is approved under accelerated approval based on the improvement of hearing sensitivity assessed by average pure tone audiometry (PTA) at Week 24. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory clinical trial.

  Limitations of Use 
  
  Otarmeni is not recommended in patients in whom preoperative imaging demonstrates that access to the inner ear is not feasible including those with abnormal mastoid pneumatization or clinically significant anatomic variations of the middle ear and inner ear.

Lunsotogene parvec-cwha, branded as Otarmeni (Regeneron Pharmaceuticals, Inc.), is an in vivo gene therapy consisting of a dual adeno-associated virus serotype 1 (AAV1) vector that delivers human OTOF complementary DNA (cDNA) encoding isoform e of the otoferlin protein under the control of a hair cell-specific promoter derived from regulatory elements of myosin 15 (Myo15). Otarmeni is intended for a one-time administration via intracochlear infusion, where the dual AAV1 vector transduces inner hair cells of the cochlea to express functional otoferlin protein. Otoferlin is a calcium sensor critical for synaptic vesicle fusion and neurotransmitter release at the ribbon synapse between inner hair cells and the auditory nerve. In patients with biallelic pathogenic variants in the OTOF gene, otoferlin is absent or nonfunctional, which disrupts synaptic transmission and results in congenital profound deafness despite preservation of inner hair cell structures. Intracochlear infusion of Otarmeni results in expression of the OTOF gene primarily in inner hair cells, facilitating production of functional otoferlin protein and restoration of synaptic transmission to the auditory nerve, as demonstrated in nonclinical studies (Regeneron, 2026; Valayannopoulos et al., 2026).

Otarmeni is administered as a single-dose intracochlear infusion at a recommended dose of 7.2 × 10¹² vector genomes (vg) per ear in a total volume of 0.24 mL. Administration is performed in a surgical setting under general anesthesia by a surgeon experienced in intracochlear surgery and trained in the Otarmeni administration procedure. The surgical approach includes a standard mastoidectomy and opening of the facial recess (posterior tympanotomy), with access to the cochlea via the round window membrane. The procedure also includes fenestration of the lateral semicircular canal to allow egress of displaced perilymph, placement of a catheter through the round window membrane, and controlled infusion using a syringe pump at 0.9 mL/hour for 16 minutes, followed by a 5-minute hold before catheter removal. The prescribing information recommends consideration of intraoperative facial nerve monitoring (IFNM) throughout the procedure. Bilateral treatment, if applicable, may be performed during a single surgical session. Perioperative management includes systemic oral corticosteroids for prophylaxis against inflammatory and immunological responses beginning on the day of infusion and tapered over 4 weeks, antibiotic administration before incision, and age-appropriate vaccination, including vaccination against microorganisms that cause meningitis because meningitis is a known risk of inner ear surgery. Otarmeni is not recommended in patients in whom preoperative imaging demonstrates that access to the inner ear is not feasible, including those with abnormal mastoid pneumatization or clinically significant anatomic variations of the middle ear and inner ear.

Although there are no known contraindications, Otarmeni carries a labeled warning for procedure-related risks associated with intracochlear surgery. Procedure-related adverse reactions may include vertigo, tinnitus, cerebral spinal fluid leak, ipsilateral facial paresis, ipsilateral change in taste, meningitis, wound infection, mastoiditis, numbness around the ear, blood or fluid collection at the surgical site, and labyrinthitis. Providers should monitor for surgical complications. Therapy is not recommended for patients with anatomy that prevents safe access to the inner ear. In the clinical trial, many of the adverse events were temporally associated with the surgical delivery approach, and all remaining adverse events were transient. No adverse events led to study discontinuation or dose interruption (Valayannopoulos et al., 2026).

The most common adverse reactions (incidence of 5% or more) reported in clinical trials were otitis media (38%), vomiting (33%), nausea (29%), dizziness (21%), procedural pain (17%), gait disturbance (8%), and nystagmus (8%). Other clinically significant adverse reactions each occurring in 1 patient included transient balance disorder (4%), abnormal otoacoustic emissions (4%), and wound dehiscence (4%) (Regeneron, 2026b).

OTOF-Related Hearing Loss

OTOF-related hearing loss is an auditory synaptopathy caused by biallelic pathogenic variants in the OTOF gene, which encodes otoferlin, a protein essential for calcium-mediated synaptic vesicle release in cochlear inner hair cells. This condition is typically characterized by congenital or prelingual, severe-to-profound bilateral hearing loss, with preserved otoacoustic emissions and abnormal auditory brainstem responses reflecting impaired signal transmission between inner hair cells and the auditory nerve. Because otoacoustic emissions primarily assess outer hair cell function, newborn hearing screening programs that rely only on otoacoustic emission testing may fail to detect OTOF-related hearing loss (Azaiez et al., 2026). Hearing does not spontaneously improve, and prior management has relied on hearing aids or cochlear implants, which may provide benefit but do not fully restore natural hearing (Azaiez et al., 2026; Valayannopoulos et al., 2026).

Genetic mutations cause about half of congenital hearing loss. Variants in the OTOF gene account for 2% to 8% of inherited, non-syndromic cases (FDA, 2026). Patients with two nonworking copies do not produce otoferlin, disrupting sound signal transmission. Delayed diagnosis can lead to missed treatment windows and lasting speech and language delays (FDA, 2026). Despite profound hearing loss, young children with otoferlin deficiency have cellular structures of the inner ear that remain intact, which provides the biologic rationale for introducing otoferlin protein with AAV-based gene therapy to restore natural hearing (Valayannopoulos et al., 2026). Prior to the approval of Otarmeni, no disease-modifying treatments existed for OTOF-related deafness (FDA, 2026).

On April 23, 2026, the U.S. FDA approved lunsotogene parvec-cwha (Otarmeni), as the first-ever dual AAV vector-based gene therapy, for the treatment of pediatric and adult patients with severe-to-profound and profound sensorineural hearing loss (any frequency greater than 90 dB HL) associated with molecularly confirmed biallelic variants in the OTOF gene, preserved outer hair cell function, and no prior cochlear implant in the same ear (FDA, 2026; Regeneron, 2026b). The FDA granted accelerated approval based on the effectiveness and safety outcomes from the DB-OTO-001 study (NCT05788536).

The DB-OTO-001 study (NCT05788536, CHORD) is an ongoing, multicenter, open-label, single-arm, first-in-human registrational trial that evaluated Otarmeni in pediatric patients with biallelic OTOF gene–associated severe-to-profound and profound sensorineural hearing loss (defined as >90 dB HL on pure-tone audiometry averaged across 0.5, 1, 2, and 4 kHz and auditory brainstem response), clinical markers of intact outer hair-cell function (distortion-product otoacoustic emissions or cochlear microphonics in the treated ear or ears), no evidence of temperature-sensitive fluctuations in hearing, and who were considered candidates for cochlear implant. Key exclusion criteria included previous gene therapy or a cochlear implant in the ear designated for DB-OTO. A total of 24 children aged 10 months to 16 years (median age, 2 years) received a single intracochlear infusion of 7.2×10¹² vector genomes in 0.24 mL per ear, administered unilaterally (n=10) or bilaterally (n=14). Of the 24 patients, 20 had completed efficacy assessments at Week 24. Among these 20 patients, five had a contralateral cochlear implant in place prior to enrollment, two received a cochlear implant in the contralateral ear during the same surgical session for Otarmeni administration, and two had bilateral hearing aids before treatment. The primary efficacy endpoint was achievement of a hearing sensitivity threshold of ≤70 dB HL by average pure-tone audiometry (PTA) at Week 24, and the key secondary endpoint was an auditory brainstem response (ABR) to a click stimulus of ≤90 dB normalized hearing level (nHL) at Week 24. Among evaluable patients, the primary endpoint was achieved in 80% (16/20; 95% CI, 56% to 94%)—an outcome not observed in the untreated natural history of the condition—and the key secondary endpoint was achieved in 70% (14/20; 95% CI, 46% to 88%). At Week 24, 45% (9/20) achieved PTA thresholds ≤45 dB HL (ability to hear soft conversational speech level) and 15% (3/20) achieved ≤25 dB HL (normal hearing level, i.e., ability to hear whispers). One patient received a cochlear implant as rescue treatment approximately 8 months after Otarmeni administration in the same ear following determination of treatment failure. In the initial 12-patient cohort reported in the clinical trial publication, 75% (9/12; 95% CI, 43 to 95; P=1.1×10⁻¹³) met both the primary and key secondary endpoints, six could hear soft speech without assistive devices (≤45 dB HL), and three achieved normal hearing sensitivity (≤25 dB HL). At Week 48, 12 patients were evaluated; all 9 patients who had responded at Week 24 maintained their response, and one additional patient who had not initially achieved response at Week 24 achieved an average PTA threshold of ≤70 dB HL, resulting in 10 of 12 (83%) achieving ≤70 dB HL. Eight of 12 (67%) achieved ≤45 dB HL, 5 of 12 (42%) achieved ≤25 dB HL, and 9 of 12 (75%) demonstrated ABR responses ≤90 dB nHL. In the initial 12-patient cohort, 67 adverse events were reported, none leading to study discontinuation; two serious adverse events resolved without sequelae (Valayannopoulos et al., 2026). In the full 24-patient safety population, the most common adverse reactions (≥5%) included otitis media (38%), vomiting (33%), nausea (29%), dizziness (21%), procedural pain (17%), gait disturbance (8%), and nystagmus (8%) (Regeneron, 2026b). These findings support that DB-OTO gene therapy improves hearing in patients with OTOF-related deafness and may enable restoration of natural acoustic hearing in some patients (Regeneron, 2026b; Valayannopoulos et al., 2026).

Continued approval may be contingent upon assessment of durability of hearing improvement along with verification of treatment effects on clinical measures of speech development and quality of life. The FDA-approval was issued 61 days after Biologics License Application (BLA) filing, marking the sixth approval under the Commissioner's National Priority Voucher (CNPV) pilot program and the first gene therapy product approved under the program (FDA, 2026).

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References