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Regeneron’s Gene Therapy DB-OTO Shows Promising Results in Treating Genetic Hearing Loss, Regulatory Submission Anticipated
Regeneron Pharmaceuticals (NASDAQ: REGN) announced compelling results from its pivotal CHORD trial evaluating DB-OTO, an investigational gene therapy targeting profound OTOF-related hearing loss. The data, published in the prestigious *New England Journal of Medicine* and presented at the American Academy of Otolaryngology-Head and Neck Surgery Foundation (AAO-HNSF) meeting on October 12, 2025, demonstrate significant hearing improvements in pediatric patients. The company plans to file for U.S. regulatory approval later in 2025, pending discussions with the Food and Drug Administration (FDA).
The CHORD trial, a Phase 1/2 study, enrolled children with profound hearing loss caused by mutations in the *OTOF* gene. These mutations disrupt the production of otoferlin, a protein crucial for sound transmission from the inner ear’s sensory cells to the auditory nerve. DB-OTO aims to deliver a functional copy of the *OTOF* gene directly into the cochlea via a surgical procedure similar to cochlear implantation. This targeted approach is designed to restore natural hearing function in patients who would otherwise rely on hearing aids or cochlear implants.
Key Findings from the CHORD Trial:
* **Significant Hearing Improvement:** 11 out of 12 participants exhibited clinically meaningful hearing improvements. This was assessed by behavioral pure tone audiometry (PTA), the gold standard for measuring hearing sensitivity.
* **Return to Normal Hearing:** Remarkably, 3 participants achieved normal hearing sensitivity, capable of detecting whispers.
* **Primary Endpoint Met:** The trial successfully met its primary endpoint, with 9 participants achieving a hearing threshold of ≤70 dBHL (decibel hearing level) at week 24. This signifies a level of hearing that typically eliminates the need for traditional cochlear implants.
* **Auditory Brainstem Response (ABR):** 9 participants also showed a positive auditory brainstem response (ABR) at ≤90 dB, a key secondary endpoint. ABR provides objective confirmation of improved hearing function by measuring electrical brainstem activity in response to sound.
* **Durability of Effect:** 8 participants with extended follow-up (up to 72 weeks) maintained stable or continued to improve their hearing.
* **Speech Improvements:** Among the 3 participants with at least 48 weeks of follow-up, all demonstrated significant improvements in speech perception. One participant could identify single and double-syllable words without visual cues and effectively respond to sounds and speech in noisy environments.
* **Safety Profile:** Both the surgical procedure and DB-OTO were generally well tolerated, with no adverse events directly related to the gene therapy itself. Transient post-surgical vestibular events (e.g., nystagmus, nausea, dizziness) were observed in some participants, but these resolved fully.
Positive
- 11 of 12 participants showed clinically meaningful hearing improvements
- 3 participants achieved normal hearing sensitivity (whisper detection)
- Trial met primary endpoint: 9 participants ≤70 dBHL at week 24
- 9 participants demonstrated ABR ≤90 dB (key secondary endpoint)
- Hearing stability or improvement up to 72 weeks in 8 participants
- No DB-OTO-related adverse findings reported across 12 participants
Negative
- Two serious adverse events occurred: cochlear implant surgery and a vaccination
- Some participants had transient vestibular events (nystagmus, nausea, dizziness)
- U.S. regulatory submission timing uncertain—pending FDA discussions in 2025
Insights
DB-OTO’s pivotal CHORD data show broad, durable hearing gains and a planned U.S. regulatory filing later in the year.
These results describe a single intracochlear dose of DB-OTO producing clinically meaningful hearing improvement in 11 of 12 pediatric participants, including three achieving normal hearing sensitivity and nine meeting the primary endpoint at week 24 by behavioral pure tone audiometry. The data also report auditory brainstem response success in nine participants, durable or improving outcomes through up to 72 weeks for eight participants, and speech gains in the three with ≥48 weeks follow-up; both the surgical procedure and the therapy were reported as well tolerated with no DB-OTO–related adverse findings.
The regulatory path is explicit and near-term: a U.S. regulatory submission is planned later this year pending FDA discussions, and DB-OTO already holds multiple FDA designations (Orphan Drug, Rare Pediatric Disease, Fast Track, and RMAT) plus EMA Orphan status. Monitor filing timing, FDA feedback, and confirmatory safety/efficacy in larger cohorts and longer follow-up over the next 6–18 months to assess whether durability and safety scale beyond this 12-participant dataset.
10/12/2025 – 10:18 AM
**Financial Implications and Market Opportunity**
The positive results from the CHORD trial represent a watershed moment in the treatment of genetic hearing loss and could position Regeneron as a leader in the emerging field of gene therapy for auditory disorders. OTOF-related hearing loss, while rare (affecting an estimated 20-50 newborns per year in the U.S.), represents a significant unmet medical need. The current standard of care, hearing aids and cochlear implants, do not fully restore natural hearing function. DB-OTO offers the potential for a one-time treatment that could provide lasting hearing improvement and eliminate the need for these devices.
Analysts estimate that the market for gene therapies targeting hearing loss could reach billions of dollars in the coming years. If approved, DB-OTO would be a first-in-class treatment and could command a premium price, contributing significantly to Regeneron’s future revenue stream. The company’s existing portfolio of medications and strong track record in drug development further bolster its position as a key player in the biotechnology sector.
**Technical Analysis and Future Development**
DB-OTO utilizes a dual adeno-associated virus (AAV) vector system to deliver the functional *OTOF* gene specifically to hair cells within the cochlea. This cell-selective approach, driven by a proprietary *Myo15* promoter, aims to minimize off-target effects and ensure that the gene is expressed only in the appropriate cells.
The CHORD trial results underscore the success of this targeted gene delivery strategy. However, further research is needed to fully understand the long-term durability of DB-OTO’s effects and to assess its safety profile in larger patient populations. Regeneron is also exploring other gene targets for different forms of genetic hearing loss, expanding its auditory program to address a broader range of auditory disorders.
The planned regulatory submission to the FDA will be a key milestone for DB-OTO. Given the Orphan Drug, Rare Pediatric Disease, Fast Track, and Regenerative Medicine Advanced Therapy designations already granted by the FDA, the agency is expected to expedite the review process. Successful approval would not only provide a new treatment option for patients with OTOF-related hearing loss but also validate Regeneron’s gene therapy platform and open doors for further development of novel therapies for other genetic diseases.
FAQ
What were the CHORD trial results for Regeneron’s DB-OTO (REGN) on Oct 12, 2025?
Updated CHORD data show 11 of 12 participants had clinically meaningful hearing gains; 3 reached normal hearing sensitivity; results published in NEJM and presented at AAO-HNSF.
How many CHORD participants met the DB-OTO primary endpoint (REGN) at week 24?
9 participants met the primary endpoint with hearing thresholds ≤70 dBHL at week 24.
Did DB-OTO (REGN) show durable hearing improvements and for how long?
Hearing stability or continued improvement was observed in 8 participants with follow-up visits up to 72 weeks.
What safety events were reported with DB-OTO in the CHORD trial?
No DB-OTO-related adverse findings were reported; two serious adverse events occurred (one cochlear implant surgical complication, one post-vaccination), and some transient vestibular events resolved.
Will Regeneron file for U.S. approval of DB-OTO (REGN) in 2025?
Regeneron plans a U.S. regulatory submission later in 2025, pending discussions with the FDA.
What functional speech improvements were seen after DB-OTO treatment in CHORD?
Among three participants assessed at ≥48 weeks, all showed significant speech gains; one could identify one- and two-syllable words without visual cues and respond in noisy settings.
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