Latest DB-OTO Results Demonstrate Clinically Meaningful Hearing Improvements in Nearly All Children with Profound Genetic Hearing Loss in CHORD Trial
Regeneron Pharmaceuticals (NASDAQ: REGN) reported promising results from the Phase 1/2 CHORD trial of DB-OTO, a gene therapy for profound genetic hearing loss caused by otoferlin gene variants. Of 12 treated children, 10 out of 11 with post-treatment assessments showed notable hearing improvements.
The first child treated, at 10 months old, showed near-normal hearing levels across key speech frequencies at 48 weeks, with continued progress at 72 weeks, including the ability to identify words at conversational levels. Among five participants with 24-week assessments, three achieved 'nearly normal' or normal hearing levels.
The treatment was well-tolerated across all participants, with only temporary post-surgical vestibular effects in five patients that resolved within 6 days. DB-OTO has received multiple FDA designations including Orphan Drug, Rare Pediatric Disease, Fast Track, and Regenerative Medicine Advanced Therapy, as well as EMA Orphan Drug Designation.
Regeneron Pharmaceuticals (NASDAQ: REGN) ha riportato risultati promettenti dallo studio CHORD di fase 1/2 su DB-OTO, una terapia genica per la perdita auditiva genetica profonda causata da varianti del gene otoferlina. Dei 12 bambini trattati, 10 su 11 con valutazioni post-trattamento hanno mostrato notevoli miglioramenti dell'udito.
Il primo bambino trattato, a 10 mesi, ha mostrato livelli di udito quasi normali su frequenze vocali chiave a 48 settimane, con progressi continui a 72 settimane, inclusa la capacità di identificare parole a livelli conversazionali. Tra i cinque partecipanti con valutazioni a 24 settimane, tre hanno raggiunto livelli di udito 'quasi normali' o normali.
Il trattamento è stato ben tollerato da tutti i partecipanti, con solo effetti vestibolari post-chirurgici temporanei in cinque pazienti, risolti entro 6 giorni. DB-OTO ha ricevuto molteplici designazioni dalla FDA, tra cui Farmaco Orfano, Malattia Pediatrica Rara, Percorso Veloce e Terapia Avanzata di Medicina Rigenerativa, oltre alla Designazione di Farmaco Orfano dell'EMA.
Regeneron Pharmaceuticals (NASDAQ: REGN) informó resultados prometedores del ensayo CHORD de fase 1/2 de DB-OTO, una terapia génica para la pérdida auditiva genética profunda causada por variantes del gen otoferlina. De 12 niños tratados, 10 de 11 con evaluaciones posteriores al tratamiento mostraron notables mejoras en la audición.
El primer niño tratado, a los 10 meses, mostró niveles de audición casi normales en frecuencias clave del habla a las 48 semanas, con un progreso continuo a las 72 semanas, incluida la capacidad de identificar palabras a niveles de conversación. Entre cinco participantes con evaluaciones a las 24 semanas, tres lograron niveles de audición 'casi normales' o normales.
El tratamiento fue bien tolerado entre todos los participantes, con solo efectos vestibulares postquirúrgicos temporales en cinco pacientes que se resolvieron en 6 días. DB-OTO ha recibido múltiples designaciones de la FDA, incluyendo Medicamento Huérfano, Enfermedad Pediátrica Rara, Vía Rápida y Terapia Avanzada de Medicina Regenerativa, así como la Designación de Medicamento Huérfano de la EMA.
레제너론 제약 (NASDAQ: REGN)은 오토페를린 유전자 변이에 의해 발생하는 심각한 유전적 청력 손실을 위한 유전자 치료제 DB-OTO의 1/2상 CHORD 시험에서 유망한 결과를 보고했습니다. 12명의 치료를 받은 어린이 중 11명의 후속 평가를 받은 10명이 눈에 띄는 청력 개선을 보였습니다.
10개월 된 첫 번째 치료 아동은 48주차에 주요 음성 주파수에서 거의 정상적인 청력 수준을 보였고, 72주차까지도 지속적인 발전을 보여 대화 수준에서 단어를 식별하는 능력을 포함했습니다. 24주 평가를 받은 5명의 참가자 중 3명이 '거의 정상' 또는 정상 청력 수준을 달성했습니다.
치료는 모든 참가자에게 잘 견뎌졌으며, 5명의 환자에게서만 일시적인 수술 후 전정 효과가 나타났고, 이는 6일 이내에 해결되었습니다. DB-OTO는 FDA로부터 고아약, 희귀 소아 질환, 신속 승인, 재생 의학 고급 치료 등 여러 가지 지정을 받았으며, EMA 고아약 지정도 받았습니다.
Regeneron Pharmaceuticals (NASDAQ: REGN) a rapporté des résultats prometteurs de l'essai CHORD de phase 1/2 sur DB-OTO, une thérapie génique pour la perte auditive génétique profonde causée par des variantes du gène otoferline. Parmi les 12 enfants traités, 10 sur 11 ayant subi des évaluations après traitement ont montré des améliorations auditives notables.
Le premier enfant traité, âgé de 10 mois, a montré des niveaux d'audition presque normaux dans les fréquences vocales clés à 48 semaines, avec des progrès continus à 72 semaines, y compris la capacité d'identifier des mots à des niveaux de conversation. Parmi cinq participants ayant subi des évaluations à 24 semaines, trois ont atteint des niveaux d'audition 'presque normaux' ou normaux.
Le traitement a été bien toléré par tous les participants, avec seulement des effets vestibulaires post-chirurgicaux temporaires chez cinq patients, qui se sont résolus en 6 jours. DB-OTO a reçu plusieurs désignations de la FDA, y compris Médicament Orphelin, Maladie Pédiatrique Rare, Voie Rapide et Thérapie Avancée en Médecine Régénérative, ainsi que la désignation de Médicament Orphelin de l'EMA.
Regeneron Pharmaceuticals (NASDAQ: REGN) berichtete über vielversprechende Ergebnisse aus der Phase 1/2 CHORD-Studie zu DB-OTO, einer Gentherapie für tiefgreifenden genetischen Hörverlust, der durch Varianten des Otoferlin-Gens verursacht wird. Von 12 behandelten Kindern zeigten 10 von 11 mit Nachuntersuchungen nach der Behandlung bemerkenswerte Hörverbesserungen.
Das erste behandelte Kind, 10 Monate alt, wies nach 48 Wochen nahezu normale Hörniveaus in wichtigen Sprachfrequenzen auf und zeigte auch nach 72 Wochen weiterhin Fortschritte, einschließlich der Fähigkeit, Wörter auf Gesprächsniveau zu identifizieren. Unter fünf Teilnehmern mit 24-Wochen-Bewertungen erreichten drei 'nahezu normale' oder normale Hörniveaus.
Die Behandlung wurde von allen Teilnehmern gut vertragen, wobei bei fünf Patienten nur vorübergehende vestibuläre Effekte nach der Operation auftraten, die innerhalb von 6 Tagen abklangen. DB-OTO erhielt mehrere FDA-Bezeichnungen, darunter Orphan Drug, Rare Pediatric Disease, Fast Track und Regenerative Medicine Advanced Therapy sowie die EMA Orphan Drug Designation.
- 10 out of 11 assessed patients showed notable hearing improvements
- First treated patient achieved near-normal hearing levels across key speech frequencies
- 3 out of 5 patients reached normal or nearly normal hearing levels at 24 weeks
- Treatment demonstrated strong safety profile with no serious adverse events
- Multiple FDA and EMA designations received, potentially expediting approval process
- One participant showed no improvement in hearing at 24 weeks post-treatment
- Five patients experienced temporary post-surgical side effects
Insights
The latest CHORD trial results represent a significant breakthrough in genetic medicine, particularly in treating otoferlin-related hearing loss. The 91% response rate (10 out of 11 evaluable patients) demonstrates exceptional clinical efficacy, while the successful bilateral treatments open new therapeutic possibilities.
The durability data is particularly compelling, with 72-week follow-up showing sustained benefits in the first treated patient. The achievement of normal hearing levels (≤25 dBHL) in multiple patients is remarkable for a genetic therapy targeting a sensory organ. This level of restoration allows for normal speech recognition and development, potentially eliminating the need for conventional hearing aids or cochlear implants.
From a regulatory perspective, the multiple expedited designations (Orphan Drug, Fast Track, RMAT) suggest an accelerated path to market. The clean safety profile, with only transient post-surgical effects, strengthens the therapy's commercial prospects. The surgical approach, leveraging familiar cochlear implantation techniques, should facilitate adoption among otolaryngologists.
For Regeneron, DB-OTO could represent a significant market opportunity. While otoferlin-related hearing loss is rare, affecting approximately 1 in 50,000 births, the potential for premium pricing typical of genetic therapies, combined with the dramatic clinical benefits, suggests substantial commercial potential. The therapy's success also validates Regeneron's expansion into genetic medicine beyond its traditional focus areas.
The most compelling aspect is the transformation in quality of life, particularly in young children where early intervention could prevent developmental delays. The ability to restore near-normal hearing and enable natural speech development represents a paradigm shift in treating genetic hearing loss.
As presented at ARO, 10 of 11 children with at least one post-treatment assessment showed notable improvements in hearing
Speech and development progress followed dramatic improvements in hearing in first child treated in the trial
TARRYTOWN, N.Y., Feb. 24, 2025 (GLOBE NEWSWIRE) -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced updated data for the investigational gene therapy DB-OTO from the Phase 1/2 CHORD trial in 12 children who have profound genetic hearing loss due to variants of the otoferlin (OTOF) gene. These include 72-week results showing speech and development progress in the first child dosed at 10 months of age, as well as initial results in 11 children (aged 10 months to 16 years old) – three of whom received DB-OTO bilaterally (in both ears). The latest results were presented in an oral presentation at the Association for Research in Otolaryngology’s (ARO) 48th Annual MidWinter Meeting.
“Sound is a significant part of the human experience that connects us to each other and our environment,” said Jay T. Rubinstein, M.D., Ph.D., Virginia Merrill Bloedel Professor of Otolaryngology and Bioengineering and Director, Bloedel Hearing Research Center, University of Washington School of Medicine, and a CHORD clinical trial investigator. “A year after treatment in one ear with DB-OTO, a child born profoundly deaf was able to enjoy music, engage in imaginative play and participate in bedtime reading when the cochlear implant on their other ear was removed. These seemingly small interactions are life-changing for these children as well as their families and these results continue to underscore the revolutionary promise of DB-OTO as a potential treatment for otoferlin-related hearing loss.”
In the trial, 12 participants have received DB-OTO to date – of whom nine were administered an intracochlear injection in one ear and three received it bilaterally. The surgical procedure to administer DB-OTO leverages an approach similar to cochlear implantation, which enables use in young infants.
As presented at ARO, 48-week results from the first participant dosed in the trial showed improvement of hearing to near-normal levels across key speech frequencies. This included hearing thresholds that were within normal limits (0.25-2.0 kHz) in most speech-relevant frequencies and corroborated with positive auditory brainstem responses (ABRs). Particularly encouraging were results from formal speech perception tests in which the child demonstrated improvement from week 48 to week 72 and correctly identified words – such as mommy, cookies and airplane – that were presented at a conversational level without any visual cues.
Among the 11 participants with at least one post-treatment assessment, 10 demonstrated a notable response, with improved hearing at various decibel hearing levels (dBHL). Additionally, among five participants with 24-week assessments, three experienced improvements in average hearing thresholds to “nearly normal” (n=1; ≤40 dBHL) or normal (n=2; ≤25 dBHL) hearing levels. All ABR responses were corroborated by hearing improvements assessed by pure tone audiometry (PTA). One participant has not experienced a change from their baseline hearing at 24 weeks post-dosing.
Across all 12 participants, both the surgical procedure and DB-OTO were well tolerated, and there were no adverse events or serious adverse events considered related to DB-OTO. Five of 12 participants experienced transient post-surgical vestibular adverse events (e.g., nystagmus, nausea, dizziness, vomiting), which resolved within 6 days of dosing.
DB-OTO received Orphan Drug, Rare Pediatric Disease, Fast Track and Regenerative Medicine Advanced Therapy designations from the U.S. Food and Drug Administration and Orphan Drug Designation was granted by the European Medicines Agency. The potential use of DB-OTO for otoferlin-related hearing loss is currently under clinical investigation, and its safety and efficacy have not been evaluated by any regulatory authority.
About Otoferlin-related Hearing Loss
Congenital deafness (hearing loss present at birth) is a significant unmet medical need that affects approximately 1.7 out of every 1,000 children born in the U.S. and approximately half of these cases have genetic causes. However, otoferlin-related hearing loss is ultra-rare. This specific condition is caused by variants in the OTOF gene, which leads to a lack of a functional otoferlin protein that is critical for the communication between the sensory cells of the inner ear and the auditory nerve.
About the CHORD Trial
The CHORD trial is an ongoing, Phase 1/2 first-in-human, multicenter, open-label trial to evaluate the safety, tolerability and preliminary efficacy of DB-OTO in infants, children and adolescents with otoferlin variants.
Currently enrolling children across sites in the U.S., United Kingdom and Spain (<18 years of age), CHORD is being conducted in two parts. In the initial dose-escalation cohort (Part A), participants receive a single intracochlear injection of DB-OTO in one ear, and in the expansion cohort (Part B), participants receive simultaneous single intracochlear injections of DB-OTO in both ears at the selected dose from Part A.
Hearing improvements were assessed by PTA and ABR. PTA is considered by auditory experts to be the gold standard measurement of hearing and is measured through behavioral responses to sound (e.g., turning head towards sound) that is emitted at different intensity levels and measured in decibels (dB). ABR corroborates these behavioral responses, serving as an objective confirmation of hearing function, and is measured through electrical brainstem responses to sound emitted at different dBs. At baseline, all participants had no behavioral (PTA) or electrophysiological (ABR) responses at maximum sound levels (≥100 dB).
Additional information about the trial, including enrollment, can be obtained by contacting clinicaltrials@regeneron.com.
About DB-OTO and the Regeneron Auditory Program
DB-OTO is an investigational cell-selective, dual adeno-associated virus (AAV) vector gene therapy designed to provide durable, physiological hearing to individuals with profound, congenital hearing loss caused by variants of the OTOF gene. The treatment aims to deliver a working copy to replace the faulty OTOF gene using a modified, non-pathogenic virus that is delivered via an injection into the cochlea under general anesthesia (similar to the procedure used for cochlear implantation). In this gene therapy, the newly introduced OTOF gene is under the control of a proprietary cell-specific Myo15 promoter, which is intended to restrict expression only to inner hair cells that normally express otoferlin.
In addition to OTOF, Regeneron is committed to investigating several other targets for genetic forms of hearing loss, including GJB2.
About Regeneron
Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents, develops and commercializes life-transforming medicines for people with serious diseases. Founded and led by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to numerous approved treatments and product candidates in development, most of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, neurological diseases, hematologic conditions, infectious diseases, and rare diseases.
Regeneron pushes the boundaries of scientific discovery and accelerates drug development using our proprietary technologies, such as VelociSuite®, which produces optimized fully human antibodies and new classes of bispecific antibodies. We are shaping the next frontier of medicine with data-powered insights from the Regeneron Genetics Center® and pioneering genetic medicine platforms, enabling us to identify innovative targets and complementary approaches to potentially treat or cure diseases.
For more information, please visit www.Regeneron.com or follow Regeneron on LinkedIn, Instagram, Facebook or X.
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This press release includes forward-looking statements that involve risks and uncertainties relating to future events and the future performance of Regeneron Pharmaceuticals, Inc. (“Regeneron” or the “Company”), and actual events or results may differ materially from these forward-looking statements. Words such as “anticipate,” “expect,” “intend,” “plan,” “believe,” “seek,” “estimate,” variations of such words, and similar expressions are intended to identify such forward-looking statements, although not all forward-looking statements contain these identifying words. 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