Catching up but still miles behind—a patient registry for otoferlin
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The approval of investigational drugs for five adeno-associated virus-based gene replacement therapies marked a historic milestone in the journey to treat the first hereditary form of hearing impairment, auditory synaptopathy, caused by deleterious variants in the otoferlin gene (OTOF, DFNB9)1. Three of these approvals were granted by the U.S. Food and Drug Administration and European Medicines Agency in 2022/2023 and represented pivotal advancements, paving the way for clinical trials by one French-based and two American-based companies. In late 2023, the earliest results from the first-in-human otoferlin trial were presented at the European Society of Gene and Cell Therapy meeting in Brussels, Belgium (https://www.esgct.eu/) by Dr. Shu Yilai and colleagues from China, making headlines in the press (https://www.technologyreview.com/2023/11/01/1082740/china-gene-therapty-deafness-hearing/). This pioneering work, published in January 20242,3, added substantial knowledge to the unfolding narrative, which also includes a recent press release from Akouos describing a successful one-month follow-up in a single treated patient (https://www.genengnews.com/topics/translational-medicine/gene-therapy-restores-hearing-in-11-year-old-after-just-one-month/). While early trial reports are cautiously optimistic, offering promising outcomes on safety and efficacy to date, open questions remain, including the durable safety and efficacy of these therapies in humans, as well as the implementation of harmonized and appropriate outcome measures. As we anticipate the development of efficient hearing-restoring OTOF gene therapies, we describe the inception of the first patient registry for patients with otoferlin-related auditory synaptopathy and the first gene-specific registry for an isolated form of hearing loss (NCT05946057), drawing inspiration from the existing registries for syndromic forms of hearing loss. This way, we mark yet another step forward in the evolving landscape of clinical trials on otoferlin-related auditory synaptopathy.
Abstract
The approval of investigational drugs for five adeno-associated virus-based gene replacement therapies marked a historic milestone in the journey to treat the first hereditary form of hearing impairment, auditory synaptopathy, caused by deleterious variants in the otoferlin gene (OTOF, DFNB9)1. Three of these approvals were granted by the U.S. Food and Drug Administration and European Medicines Agency in 2022/2023 and represented pivotal advancements, paving the way for clinical trials by one French-based and two American-based companies. In late 2023, the earliest results from the first-in-human otoferlin trial were presented at the European Society of Gene and Cell Therapy meeting in Brussels, Belgium (https://www.esgct.eu/) by Dr. Shu Yilai and colleagues from China, making headlines in the press (https://www.technologyreview.com/2023/11/01/1082740/china-gene-therapty-deafness-hearing/). This pioneering work, published in January 20242,3, added substantial knowledge to the unfolding narrative, which also includes a recent press release from Akouos describing a successful one-month follow-up in a single treated patient (https://www.genengnews.com/topics/translational-medicine/gene-therapy-restores-hearing-in-11-year-old-after-just-one-month/). While early trial reports are cautiously optimistic, offering promising outcomes on safety and efficacy to date, open questions remain, including the durable safety and efficacy of these therapies in humans, as well as the implementation of harmonized and appropriate outcome measures. As we anticipate the development of efficient hearing-restoring OTOF gene therapies, we describe the inception of the first patient registry for patients with otoferlin-related auditory synaptopathy and the first gene-specific registry for an isolated form of hearing loss (NCT05946057), drawing inspiration from the existing registries for syndromic forms of hearing loss. This way, we mark yet another step forward in the evolving landscape of clinical trials on otoferlin-related auditory synaptopathy.
참고문헌 (10)
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