Regeneron Pharmaceuticals’ investigational gene therapy DB-OTO improved hearing in two young children with “profound genetic deafness” since birth, according to the company’s Wednesday oral presentation at the 2024 American Society of Gene & Cell Therapy annual meeting in Baltimore.

根据Regeneron Pharmaceuticals周三在巴尔的摩举行的2024年美国基因与细胞治疗学会年会上的口头报告，Regeneron Pharmaceuticals的研究性基因治疗DB-OTO改善了两名自出生以来患有“严重遗传性耳聋”的幼儿的听力。

One patient returned to normal hearing levels within 24 of treatment, as measured by auditory brainstem response (ABR) and the gold-standard pure tone audiometry (PTA)—both of which are validated methods of evaluating hearing function. The patient was dosed with DB-OTO at 11 months of age and is “one of the youngest in the world to receive a gene therapy for genetic deafness,” Regeneron said in its news release on Wednesday..

通过听觉脑干反应（ABR）和金标准纯音测听（PTA）测量，一名患者在治疗后24小时内恢复正常听力水平，这两种方法都是评估听力功能的有效方法。Regeneron在周三的新闻稿中表示，该患者在11个月大时服用了DB-OTO，是“世界上接受遗传性耳聋基因治疗的最年轻患者之一”。。

At the 24-week assessment mark, the patient showed an average 84-dB improvement from baseline across key speech frequencies. PTA found that one frequency even reached 10 dB in hearing level.

在24周的评估评分中，患者在关键语音频率上比基线平均改善了84 dB。PTA发现，一个频率的听力水平甚至达到了10分贝。

The second patient, who was given the gene therapy at four years of age, showed “initial hearing improvements” at the six-week follow-up. The patient demonstrated behavioral responses to loud sounds. The average improvement from baseline across key speech frequencies was 19 dB.

第二名患者在四岁时接受了基因治疗，在六周的随访中显示出“最初的听力改善”。患者表现出对响声的行为反应。从基线到关键语音频率的平均改善为19 dB。

Lawrence Lustig, study investigator and chairperson of Columbia University’s Department of Otolaryngology-Head & Neck Surgery, in a statement called these initial results “impressive,” adding that they “showcase the revolutionary promise of DB-OTO as a potential treatment for otoferlin-related deafness.”.

哥伦比亚大学耳鼻咽喉头颈外科系主任、研究研究员劳伦斯·卢斯蒂格在一份声明中称这些初步结果“令人印象深刻”，并补充说它们“展示了DB-OTO作为治疗耳蜗相关耳聋的潜在疗法的革命性前景。”。

Wednesday’s initial readout comes from the ongoing Phase I/II CHORD trial, a first-in-human open-label study, which is still currently enrolling patients from sites in the U.S., U.K. and Spain. In addition to efficacy, CHORD also looked at the safety of DB-OTO and found it to be well-tolerated with no treatment-related serious adverse events..

周三的初步数据来自正在进行的I/II期CHORD试验，这是第一项人体开放标签研究，目前仍在从美国、英国和西班牙的网站招募患者。除疗效外，CHORD还研究了DB-OTO的安全性，发现其耐受性良好，没有与治疗相关的严重不良事件。。

Designed to be delivered via a single sear injection, DB-OTO is a cell-selective, AAV-delivered gene therapy that works by delivering a functioning copy of the otoferlin gene, which is mutated and dysfunctional in patients with genetic hearing loss. Affecting nearly 1.7 out of every 1,000 children born in the U.S., congenital hearing loss presents a “significant unmet need,” according to Regeneron.

DB-OTO旨在通过单次sear注射进行递送，是一种细胞选择性的AAV递送基因疗法，其通过递送otoferlin基因的功能拷贝而起作用，该基因在遗传性听力损失患者中发生突变和功能障碍。据Regeneron称，先天性听力损失影响了美国每1000名出生儿童中的近1.7名，是“严重未满足的需求”。

The otoferlin gene is implicated in about half of these cases..

这些病例中约有一半涉及otoferlin基因。。

With the early results from CHORD, Regeneron follows in the footsteps of Eli Lilly, which in January 2024 revealed that its investigational otoferlin gene therapy AK-OTOF restored the hearing of an 11-year-old boy within 30 days of treatment. A day later, a Chinese research group published results in The Lancet, showing that they were able to restore hearing in five of six children treated with their own otoferlin gene therapy..

根据CHORD的早期结果，Regeneron效仿了礼来公司（Eli Lilly），礼来公司于2024年1月透露，其研究性的otoferlin基因疗法AK-OTOF在治疗后30天内恢复了一名11岁男孩的听力。一天后，一个中国研究小组在《柳叶刀》上发表了研究结果，结果表明，他们能够在接受自己的耳蜗素基因治疗的六名儿童中恢复五名的听力。。

As in the case of CHORD, the patients in these two studies had profound genetic deafness since birth.

与CHORD一样，这两项研究中的患者自出生以来就患有严重的遗传性耳聋。