Fudan University

Several small clinical trials have demonstrated that gene therapies have restored hearing in children with a rare form of genetic deafness. In an update at the Association for Research in Otolaryngology’s midwinter meeting in Anaheim, CA, Regeneron reported Monday that 10 of 11 children saw notable improvements in hearing after receiving its gene therapy for a form of deafness caused by mutations in the gene that encodes otoferlin. The Tarrytown, NY-based biotech also said that three of five children it followed for 24 weeks reached “nearly normal” or normal hearing levels. “One of these participants — the participant was in the shower — and they were perceiving something, and they could not understand what was happening,” Jonathon Whitton, head of Regeneron’s auditory global program, said in an interview. “What they realized was they never heard water in the shower before.” Meanwhile, Chinese researchers using a therapy developed by Otovia Therapeutics said Monday at the meeting that hearing was restored in all nine participants enrolled in an investigator-initiated otoferlin gene therapy trial, including one adult patient. Regeneron, Otovia and several other companies are working on gene therapies that treat hearing loss as a result of mutations in the gene for otoferlin, a key signaling protein between the ear and the brain. Back in May, Regeneron disclosed that two children had their hearing restored to the normal range about six months after receiving the therapy, which it gained from its 2023 acquisition of Decibel Therapeutics , where Whitton previously led clinical research. In its new update, Regeneron said it had dosed a total of 12 participants, though only 11 have had their first four-week assessment. Three participants received the gene therapy in both ears. One participant in Regeneron’s study did not experience a change in their hearing in the nearly six months following treatment. Some children in the study experienced side effects such as nausea, dizziness and vomiting from the surgery to receive the gene therapy in the days after the procedure. Whitton said the procedure is similar to the one used for cochlear implants in kids. Regeneron’s study is taking place in the US, Spain and the UK. Regeneron is talking to the FDA about the potential of using its current study to apply for approval of the gene therapy, according to Whitton. The form of deafness caused by mutations to the otoferlin gene is exceedingly rare, and Regeneron estimates there are less than 50 people per year in the US who are born with it. In an abstract published on ARO’s website, investigators at several institutions in China who are testing Otovia’s candidate described the gene therapy’s changes to hearing as “rapid” and taking “one month to restore most hearing.” They also reported that the therapy was more effective for younger participants, with those between the ages of 5 and 8 experiencing the most hearing restoration. An Otovia scientist told Endpoints News via email that the study has completed enrollment with 11 patients. Otovia was incubated by Fosun Health Capital in 2022, and the biotech said it’s “actively preparing for seed round financing to support our lead program.” The results from Otovia’s candidate follow those presented in May by a separate group of scientists in China, where researchers are able to quickly generate clinical data using investigator-initiated studies. In May, Yilai Shu and other researchers at Fudan University in Shanghai shared that 10 of 11 children who were born deaf had their hearing restored in an investigator-initiated study using a gene therapy developed by Refreshgene Therapeutics, a biotech based in the same city. Shu’s group this week also shared new analyses depicting how speech and hearing developed in children after they received the gene therapy and how outcomes from the experimental therapy compare to cochlear implants. Eli Lilly is also developing an otoferlin gene therapy and last year reported that it restored hearing in an 11-year-old boy who received the therapy. A French biotech called Sensorion is also doing work in this area. In December, it said it had dosed three patients in a clinical trial with its otoferlin gene therapy.

Ten of 11 children born profoundly deaf experienced some degree of hearing improvement after receiving an experimental gene therapy developed by Regeneron Pharmaceuticals.A few of the children can now hear sound at near-normal levels, like conversational speech. One, who was 10 months old when treated and has been followed for more than a year, correctly identified spoken words, like mommy, “cookies“ and “airplane,“ without visual cues in a formal test.The findings, disclosed by the company Monday alongside a presentation at a medical meeting, are a notable achievement in the development of gene therapies for congenital deafness. Other companies and groups, including Eli Lilly, France's Sensorion and researchers at Fudan University in Shanghai, are working on similar treatments as Regeneron.All aim to fix an ultra-rare form of deafness caused by mutations in a gene known as OTOF. Deep within the ear, thousands of specialized cells transmute the vibrations of sound into a signal passed to the brain via the auditory nerve. In people with this type of hearing loss, though, OTOF mutations leave those specialized cells without a vital protein called otoferlin, disrupting sound signaling.Gene therapy can deliver a working copy of OTOF into the ear, rekindling production of otoferlin and restoring signaling to the brain. Prior to Monday, initial data from the Fudan researchers, Regeneron and Lilly had shown this was possible; fuller data from the former group published last summer and, now, from Regeneron establish the potential of treatment more firmly.Were still learning, said Jonathon Whitton, head of the auditory global program at Regeneron. It's the first time anybody has been able to do something like this.The children in Regenerons study were anywhere from 10 months to 16 years old at the time of enrollment, a wide range of ages that reflects both the early stage of the trial and some of the questions Regeneron hopes to answer.When starting out, for example, Whitton noted how the company wasnt sure if, in older children, there are enough specialized ear cells for its gene therapy to have an effect. Language acquisition looks different earlier in life than later, so it wasnt completely clear whether older children would benefit equally from gene therapy.Its a pretty exciting time for the field to ask some of those questions, added Whitton.Dubbed DB-OTO, Regenerons therapy consists of benign viruses engineered to carry a functional copy of the OTOF gene. The therapy is injected directly into the cochlea via a procedure thats similar to cochlear implantation.Researchers primarily measured the effect of DB-OTO using two tests. In the first, researchers played tones of different frequencies and intensities, recording behavioral responses like participants turning their head toward sound. The second test helps to corroborate those data by measuring brain activity via electrodes placed on the head.At the start of the study, participants didnt even respond to loud sounds of 100 or 120 decibels. In the weeks after treatment, all but one of the children experienced some hearing improvement. Three of the five who reached their six-month assessment could hear sounds in the nearly normal or normal ranges, akin to regular conversation and whispers.So far, no adverse events were specifically related to DB-OTO, although five of 12 participants had transient side effects after surgery that affected their vestibular system, which controls eye movements and the bodys sense of equilibrium in space.The first trial participant developed an ear infection unrelated to gene therapy that coincided with a change in hearing on the auditory tone test around six months after treatment. Whitton noted Regeneron continues to track that participants hearing, but doesnt have concerns about the durability of benefits reported so far.For Regeneron, the results are a scientific and clinical success. Known for its protein drugs, the company has staked a substantial investment to exploring gene therapy. DB-OTO came to it via a $109 million buyout of longtime partner Decibel Therapeutics, only Regenerons second acquisition in its 37-year history.Its at the beginning of everything we're doing in genetic medicine more broadly, even outside of hearing, said Whitton.But Regenerons achievement comes at a time when gene therapy, as a field, is struggling. While more and more therapies have won U.S. approval, those milestones havent brought the sales investors originally envisioned. Funding has dried up for many developers still in the clinic as a result, while other companies have shut down. Bluebird bio, a pioneer that sells three gene therapies, recently agreed to a take-private deal worth less than $30 million upfront. Pfizer, which once had a large research presence, has essentially left the sector.This is not the best time for gene therapy, said Christos Kyratsous, co-head of Regeneron Genetic Medicines. I think it is our obligation Regenerons, the industrys and societys in general to figure out how to best develop these therapies. Were taking a long-term view.According to a spokesperson, Regeneron plans to continue enrolling patients in the trial testing DB-OTO. The company is in discussions with regulators on the therapys path forward, but thinks the current trial could potentially serve as a pivotal study that supports an approval application.If Regeneron does reach market in the years ahead, it will face some of the same challenges other gene therapy developers have wrestled with, most notably how to price and sell a complex therapy in a tiny market. According to estimates from the company, there are only 20 to 45 new patients with otoferlin-related hearing loss in the U.S. each year. '

MONDAY, Feb. 10, 2025 -- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with more rapid progression of coronary artery lesion-based plaque volume, according to a study published online Feb. 4 in Radiology . Neng Dai, M.D., from Fudan University in Shanghai, and colleagues examined the impact of SARS-CoV-2 infection on coronary inflammation and plaques using coronary computed tomography angiography. Lesions of patients with and without SARS-CoV-2 infection were compared in terms of the quantitative total and compositional percent atheroma volume (PAV) and annualized PAV change, presence of high-risk plaque, and attenuation of lesion-specific pericoronary adipose tissue (PCAT) at baseline and follow-up. Data were included for 2,108 coronary artery lesions in 690 patients with SARS-CoV-2 infection and 480 lesions in 113 patients without SARS-CoV-2 infection. The researchers found that lesions in patients with SARS-CoV-2 infection demonstrated more rapid progression of overall PAV (0.90 versus 0.62 percent per year) and noncalcified PAV (0.78 versus 0.42 percent per year) compared with lesions in patients without SARS-CoV-2 infection. Despite similar prevalence at baseline, lesions in patients with SARS-CoV-2 infection had a higher incidence of becoming high-risk plaque (21.0 versus 15.8 percent) and higher incidence of PCAT attenuation of –70.1 Hounsfield units or higher (27.1 versus 19.8 percent). A higher risk for target lesion failure was seen in lesions in patients with COVID-19 (10.4 versus 3.1 percent; adjusted hazard ratio, 2.90). "Our findings suggest that SARS-CoV-2 infection may exacerbate cardiovascular risk by accelerating the advancement of susceptible plaque types and coronary inflammation, thus offering a potential mechanistic rationale for the link between prior SARS-CoV-2 infection and adverse clinical events," the authors write. Abstract/Full Text Editorial Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.