Clinical Report: FDA Grants Accelerated Approval for OTOF Gene Therapy

Overview

The FDA has granted accelerated approval for lunsotogene parvec-cwha, a gene therapy for severe-to-profound sensorineural hearing loss due to biallelic variants in the OTOF gene. The approval is based on significant improvements in hearing thresholds observed in the CHORD trial.

Background

OTOF-related hearing loss is an ultra-rare condition affecting approximately 50 newborns annually in the US, characterized by the absence of functional otoferlin protein. This condition severely impacts auditory function, and current management options do not restore hearing. The introduction of gene therapy offers a potential breakthrough in treatment for affected patients.

Data Highlights

Key Findings

• The therapy is indicated for patients with preserved outer hair cell function and no prior cochlear implant in the treated ear.
• At 24 weeks, 80% of patients met the primary endpoint of improved hearing thresholds.
• 14 out of 20 patients demonstrated auditory brainstem responses at 90 dB or better.
• 5 of 12 patients maintained hearing thresholds within the normal range at 48 weeks.
• Common adverse events included otitis media, dizziness, procedural pain, nausea, vomiting, gait disturbance, and nystagmus. Surgical risks include meningitis, cerebrospinal fluid leak, and neurologic complications affecting the facial nerve.

Clinical Implications

Healthcare professionals should consider lunsotogene parvec-cwha as a treatment option for eligible patients with OTOF-related hearing loss, ensuring appropriate patient selection based on preserved outer hair cell function and absence of prior cochlear implants. Monitoring for adverse events will be critical for optimizing outcomes.

Conclusion

The accelerated approval of lunsotogene parvec-cwha marks a significant advancement in the treatment of genetic hearing loss, pending further confirmation of clinical benefits in ongoing trials.

References

1. Regeneron Pharmaceuticals Inc., GlobeNewswire, 2026 -- Otarmeni™ (lunsotogene parvec-cwha) Approved by FDA as First Gene Therapy for Genetic Hearing Loss
2. PubMed, 2023 -- DB-OTO Gene Therapy for Inherited Deafness
3. Retinal Physician — SUBSPECIALTY NEWS: Early anti-VEGF for DR shows no benefit, developments in gene therapy, research on IRD, and more.
4. Ophthalmology Management — FDA Grants Fast Track Designation to Sanofi’s Investigational Gene Therapy for GA
5. The ASCO Post — FDA ODAC Meeting Focuses on ‘Dangling’ Accelerated Approvals of Anti–PD-1/PD-L1 Antibodies
6. Retinal Physician — Gene Therapy for GA Receives FDA Fast Track Designation
7. FDA Grants Fast Track Designation to Sanofi’s Investigational Gene Therapy for GA
8. FDA ODAC Meeting Focuses on ‘Dangling’ Accelerated Approvals of Anti–PD-1/PD-L1 Antibodies
9. Otarmeni™ (lunsotogene parvec-cwha) Approved by FDA as
10. DB-OTO Gene Therapy for Inherited Deafness - PubMed
11. International expert consensus on gene therapy for hereditary hearing loss: Based on clinical trials - ScienceDirect