OTARMENI

OTARMENI is an FDA-registered drug product whose active ingredient is LUNSOTOGENE PARVEC-CWHA. It is labelled by Regeneron Pharmaceuticals, Inc. taken by intracochlear and marketed as a human prescription drug product. Identifiers on file: NDC 61755-062, application BLA125874, label effective 20260427. This page reproduces the FDA-approved label text so you can check what a product is, who makes it and how it is supplied before discussing it with a pharmacist or prescriber.

Across FDA labelling, products containing LUNSOTOGENE PARVEC-CWHA are most often described in connection with: inner ear, treatment pediatric, adult patients, profound sensorineural, hearing loss, frequency associated, molecularly confirmed, biallelic variants. Wording differs between labels, and the full indications section on this page takes precedence when it is present.

1 INDICATIONS AND USAGE OTARMENI is indicated for the treatment of pediatric and adult patients with severe-to-profound and profound sensorineural hearing loss (any frequency >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 [see Clinical Studies (14) ] . 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. 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 >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. ( 1 ) 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. ( 1 , 14 ) 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. ( 1 )

2 DOSAGE AND ADMINISTRATION For intracochlear infusion only. Recommended dose of OTARMENI for each ear is 7.2 × 10 12 vector genomes (vg) in a total volume of 0.24 mL, administered by a single-dose intracochlear infusion. ( 2.2 ) 2.1 Critical Dosing and Administration Information Confirm patient has biallelic, likely pathogenic or pathogenic OTOF variants. OTARMENI should be administered by a surgeon experienced in intracochlear surgery and trained in the administration procedure. Administer bilateral OTARMENI, if applicable, in a single surgical session. For prophylaxis against inflammatory and immunological responses, administer systemic oral corticosteroids equivalent in strength to prednisone at 1 mg/kg/day the day of the OTARMENI infusion, maintain the same dose for two weeks, and taper over the following two weeks. The total corticosteroid dose should not exceed 60 mg/day. For prophylaxis against post-operative infection, administer antibiotics before incision. Administer age-appropriate vaccination prior to treatment with OTARMENI. Administer vaccines at least 1 month before the first corticosteroid dose and at least 1 month after the last dose. Vaccinate patients against micro-organisms that cause meningitis before surgery as meningitis is a known risk of inner ear surgery. 2.2 Recommended Dosage For intracochlear infusion only. The recommended dose of OTARMENI for each ear is 7.2 × 10 12 vector genomes (vg) in a total volume of 0.24 mL, administered by a single-dose intracochlear infusion. 2.3 Preparation Prepare syringe containing OTARMENI using sterile technique under aseptic conditions in a Class II biological safety cabinet (BSC). Administer OTARMENI within 4 hours of puncturing the vial. Below is the list of items required for administration syringe preparation. Confirm component packaging and inspect each item prior to use and do not use if any damage is identified. One single-dose vial of OTARMENI in a sealed barrier bag (package 1 of 2) [see How Supplied/Storage and Handling (16) ] Administration Kit for use with OTARMENI (package 2 of 2) [see How Supplied/Storage and Handling (16) ] Not supplied but required: One isopropyl alcohol pad One sterile sealable plastic bag Secondary container for delivery to surgical suite Label and a pen Preparation of OTARMENI for Infusion For each treated ear, thaw one single-dose vial of OTARMENI at room temperature. The contents of the vial will thaw in approximately 30 minutes at room temperature. DO NOT thaw or warm the vial any other way. Gently invert the vial 5 times (DO NOT shake or vortex the vial). Inspect the OTARMENI vial to ensure that it is thawed, clear to slightly opalescent, and that the vial has no signs of damage. If there is any evidence of cloudiness, particulates, or color, do not use the vial. If not used immediately, store the unpunctured thawed vial in the refrigerator for up to 24 hours or at room temperature for up to 8 hours. Choose the smallest compatible syringe size, either 1 mL or 3 mL included in the kit, according to the syringe pump parameters. Discard the unused syringe. Do not open the catheter sterile packaging until transferred to the surgical suite. Prepare the septum of the OTARMENI vial using an isopropyl alcohol pad to wipe the top. Wait for the septum to dry. Secure the 21G, 1.5-inch needle onto the 1 mL or 3 mL syringe. When filling the syringe for administration, push the needle until it is completely inserted into the vial and the tip touches the bottom edge of the upright vial. Administer OTARMENI within 4 hours of puncturing the vial. Withdraw all OTARMENI vial contents into the syringe. Tilt the vial to ensure complete withdrawal. Confirm that at least 0.6 mL is available in the syringe. To prevent the introduction of air, keep the needle bevel submerged in the liquid at the bottom edge of the vial by orienting the bevel towards the vial wall (Figure 1). Figure 1: Holding the syringe with the needle pointing up, check the syringe for bubbles. If there are bubbles, gently tap the syringe with your finger until the bubbles rise to the top. Remove the needle and prime the air bubbles out of the syringe by depressing the plunger rod until the air is fully expelled and the meniscus is visible at the syringe opening. Cap and label the syringe with the following: Lot number of OTARMENI Expiration date of OTARMENI Time of preparation to ensure that product is administered within 4 hours after puncturing the vial Place the capped syringe into the sterile plastic bag and seal the bag. Place the bag into an appropriate secondary container for delivery to the surgical suite. Figure 1 Chemical Structure 2.4 Administration Administer OTARMENI in the surgical suite under general anesthesia with controlled aseptic conditions by a surgeon experienced in intracochlear surgery and trained in the OTARMENI administration procedure. Administer OTARMENI within 4 hours of puncturing the vial. The following items are required for administration: Syringe containing OTARMENI Catheter supplied with Administration Kit for use with OTARMENI (package 2 of 2) [see How Supplied/Storage and Handling (16) ] Not supplied but required: Syringe pump, capable of delivering a volume of 0.24 mL at an infusion rate of 0.9 mL/hr and is compatible with the provided 1 mL or 3 mL syringe sizes Electrode insertion forceps Fine straight pick Mayo stand Note: Only administer OTARMENI using the provided Administration Kit for use with OTARMENI . Confirm the availability of OTARMENI (1 vial and 1 Administration Kit per treated ear) prior to administration of anesthesia. Inspect each item prior to use and do not use if any damage is identified. Do not use if the sterile bag was damaged during transport or if the syringe was transported without the use of a sterile bag. Follow the steps below for intracochlear infusion: Perform a standard mastoidectomy and an opening of the facial recess (also called a posterior tympanotomy). Consider monitoring the facial nerve using intraoperative facial nerve-monitoring (IFNM) throughout the procedure. With the help of an assistant, place the syringe pump on a sterile draped Mayo stand (positioned higher than the patient's cochlea) and ensure there is enough distance to allow the catheter to reach the round window membrane. Have the non-sterile assistant remove the cap from the syringe and help attach the provided catheter (the stylet will need to be removed from the catheter). Do not flush the catheter. Slowly prime the catheter manually with minimal loss by removing all air bubbles until OTARMENI is just visible at the tip of the catheter. The anticipated priming volume is approximately 0.11 mL. Have the non-sterile assistant hold the syringe and confirm that at least 0.4 mL of OTARMENI is available in the syringe after priming. Instruct the assistant to place the syringe onto the syringe pump while you maintain control of the catheter in the sterile field. Perform a 0.5 to 1 mm fenestration of the lateral semi-circular canal (Figure 2). Do not apply suction near the fenestration of the lateral semi-circular canal. Figure 2: Lateral Semi-Circular Canal Fenestration Perforate the round window membrane using a fine straight pick or equivalent in the anterior-inferior aspect to create an opening that is sufficiently smaller than the size of the catheter to ensure a water-tight seal and prevent fluid backflow at the round window membrane (Figure 3). Do not apply suction near the round window opening. The diameter of the catheter is 1 Fr, 28 G, or 0.33 mm. Figure 3: Round Window Perforation Have the assistant program the syringe pump by selecting the brand, model, and size of the provided syringe to deliver fluid at 0.9 mL/hr with a total volume of 0.24 mL. To confirm the catheter's priming, have the assistant initiate the pump while the catheter tip is inspected. Once the presence of OTARMENI is noted at the tip of the catheter, stop the pump, and set the volume counter/limiter to zero. Instruct the assistant to note the initial volume in the syringe and verify that at least 0.3 mL of OTARMENI is available. Place the catheter tip through the round window membrane using electrode insertion forceps. Insert the catheter until the edge of the first black marker is just visible at the round window (approximately 4 mm), but no further (Figure 4). Do not over-insert the catheter. Allow the catheter to rest passively while minimizing all catheter movement during infusion. During this insertion process, some perilymph might extrude from the newly created fenestration of the lateral semicircular canal. Figure 4: Catheter Insertion If the catheter cannot be easily inserted through the round window membrane perforation, enlarge the perforation using a fine straight pick or equivalent. After confirming the pump parameters (0.24 mL at 0.9 mL/hr), instruct the assistant to initiate the pump and monitor the progression of the syringe plunger and volume counter during the entire infusion. Monitor the infusion continuously to ensure there are no interruptions, including pump alarms/alerts, flow interruption, system malfunction, or power failure. The pump should run continuously for 16 minutes. Monitor the round window membrane continuously for evidence of backflow and the fenestration in the lateral semicircular canal for evidence of forward flow. IMPORTANT: If the infusion was interrupted for any reason, pause, inspect infusion system to identify the issue, and, using clinical judgement, follow the steps below: Pause immediately and determine the time of interruption and volume delivered using the syringe markings and volume counter. Maintain catheter position. Inspect all infusion components to determine the source of the interruption. If a complete infusion of 0.24 mL has been delivered, then proceed to Step 13. If 0.24 mL has not been delivered, determine if the infusion can be resumed depending on the length and cause of the interruption, if medically appropriate. If the interruption cannot be resolved, abort the procedure. Proceed to Steps 14 – 17. After the completion of the infusion (16 minutes), leave the catheter in place for an additional 5-minute hold. Before removing the catheter, instruct the assistant to verify complete dose delivery by reading the final volume on the syringe, which should read approximately 0.24 mL less than the initial reading noted immediately before infusion. After the 5-minute hold is completed, remove the catheter from the round window membrane using the electrode insertion forceps. Do not flush the catheter. Close the round window membrane and the lateral semi-circular canal with a fascia overlay. Additionally, a bone cap can be used to reinforce the canal fenestration, while avoiding plugging the canal. Close the postauricular wound in a typical fashion. Following infusion, discard any remaining OTARMENI and disposable material according to local biosafety guidelines. Figure 2 Figure 3 Figure 4

4 CONTRAINDICATIONS None. None. ( 4 )

6 ADVERSE REACTIONS The most common adverse reactions (incidence ≥5%) include otitis media, vomiting, nausea, dizziness, procedural pain, gait disturbance, and nystagmus. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Regeneron at 1-866-500-GENE or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety data described in this section reflect exposure to OTARMENI in one study (Study DB-OTO-001) which treated 24 patients with OTOF gene associated profound sensorineural hearing loss. A total of 10 patients received unilateral dosing, and a total of 14 patients received bilateral dosing of OTARMENI at a nominal dose of 7.2 × 10 12 vg per ear. The median duration of follow-up was 45 weeks (range 9 to 115 weeks) [see Clinical Studies (14) ] . Table 1 lists the most common adverse reactions that occurred in ≥ 5% patients in Study DB-OTO-001. Table 1: Adverse Reactions Occurring in ≥5% of Patients in Study DB-OTO-001 (N=24) Adverse Reaction Overall n (%) Otitis Media 9 (38) Vomiting 8 (33) Nausea 7 (29) Dizziness 5 (21) Procedural Pain 4 (17) Gait Disturbance 2 (8) Nystagmus 2 (8) Other clinically significant adverse reactions each occurring in 1 patient included transient balance disorder (4%), abnormal otoacoustic emissions (4%), and wound dehiscence (4%).

What is OTARMENI used for?
1 INDICATIONS AND USAGE OTARMENI is indicated for the treatment of pediatric and adult patients with severe-to-profound and profound sensorineural hearing loss (any frequency >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 …

Who makes OTARMENI?
Regeneron Pharmaceuticals, Inc. is the labeler of record for OTARMENI.

What form does OTARMENI come in?
administered by intracochlear. Strengths and pack sizes vary by label, so compare the NDC on your pack with the identifier listed on this page.

Is OTARMENI prescription or over-the-counter?
The FDA label for this product is recorded as human prescription drug. Marketing status can differ between strengths and countries, so check the dispensing rules where you live.

Has OTARMENI been recalled?
No FDA recall record in our database matches this product name or manufacturer. Recall data is updated periodically, so a very recent notice may not appear here yet.

Where does this information come from?
All content is reproduced from FDA Structured Product Labelling data via openFDA. It is provided for identification and reference only and is not medical advice.