Shanghai Refreshgene Technology Co., Ltd.

Regeneron Pharmaceuticals announced further encouraging early results for its DB-OTO gene therapy for hearing loss, including 24-week data showing that the first treated patient – a 10-month-old infant – went from profound deafness at baseline to being able to detect sounds in the conversational range.The company also unveiled six-week results from a second patient who was treated at 4 years old and appears to be showing signs of a similar trajectory.The results, presented Wednesday at the American Society of Gene and Cell Therapy (ASGCT) meeting, are from Regeneron's ongoing Phase I/II CHORD trial evaluating DB-OTO as a treatment for profound hearing loss caused by mutations in the otoferlin gene.DB-OTO, a dual AAV1 vector designed for intracochlear delivery, aims to provide a full-length copy of the OTOF gene to hair cells in the inner ear. The therapy is surgically delivered using a well-established approach based on cochlear implantation, allowing direct infusion into the perilymph – the fluid-filled space of the inner ear.Preliminary data from the first patient were reported last October. The infant received a single unilateral dose of 7.2 x 1012 vector genomes of DB-OTO administered in the right ear, while a cochlear implant was placed in the left ear during the same surgical procedure.At the 24-week mark, no serious adverse events related to DB-OTO were reported. Researchers were also concerned with not damaging vestibular organs, which help people keep their balance, during surgical delivery of the therapy in the inner ear. Regeneron says vestibular function has remained normal.Unlocking auditory functionResults also showed progress in hearing ability through week 24 in the ear treated with DB-OTO. Auditory brainstem response (ABR) indicated improvement in hearing at different sound levels ranging from 45 to 85 dB, whereas before treatment, there was no response to sound at 100 dB. Additionally, an audiogram demonstrated improvement in hearing levels to within normal hearing thresholds compared to the beginning of the study, while there was no improvement in hearing intensity observed in the untreated ear with cochlear implant turned off.The first patient "entered the study with profound deafness, a sort of a level at which you couldn't even hear [a] chainsaw," explained Johnathon Whitton, who heads the Auditory Global Program at Regeneron, in an interview with FirstWord. But after treatment, "we saw responses that are in the normal sensitivity range, which is just remarkable."Corroborating the tests, parents also reported improved auditory behaviour and voice quality when the cochlear implant in the untreated ear was turned off.In a second patient, a 4-year-old child who received the same unilateral dose of DB-OTO, preliminary data demonstrated ABR and audiogram improvement through week six in the treated ear compared to baseline. No DB-OTO-related adverse events or vestibular abnormalities were observed here either."It looks very similar basically to what we saw on the first patient at that time point, so I think we're seeing something consistent starting to play out," Whitton commented.End-of-2025 filing targetRegeneron is now engaging with regulators to align on the necessary data requirements and expedite patient enrollment in the ongoing trial, targeting a filing for the end of next year. "We believe and it's a moral obligation to push as aggressively as possible now given…that very promising early efficacy data," Christos Kyratsous, co-head of Regeneron Genetic Medicines, told FirstWord.Regeneron acquired DB-OTO through its purchase of Decibel Therapeutics last year for $109 million or up to approximately $213 million if contingent value right (CVR) milestones are achieved. Alongside DB-OTO, Regeneron is also advancing other gene therapy programmes, including AAV.103 for GJB2-related hearing loss and AAV.104 for stereocilin-related hearing loss.Regeneron's efforts are part of a broader push to develop gene therapies for genetic hearing loss. Eli Lilly earlier this year reported that an 11-year-old boy born with hearing loss due to a mutation in the otoferlin gene was able to hear across all tested frequencies after being treated with a single dose of AK-OTOF, while another group involving Refreshgene Therapeutics posted positive data for the gene therapy AAV1-hOTOF.

The firm analyzes preliminary results from three investigational clinical trials across the globe NEW HAVEN, Conn., Feb. 21, 2024 /PRNewswire/ -- Auditory Insight, a leading consultancy for the hearing healthcare industry, analyzes preliminary results for gene therapy clinical trials addressing deafness and hearing loss in its Q1 2024 Research Note. Download the Research Note: Gene Therapy for Hearing Loss: Interpreting Preliminary Clinical Trial Results. In three sets of investigational clinical trials around the globe, gene therapy has transformed the hearing of children with a form of deafness from mutations in a gene called otoferlin. The children's hearing improved from profoundly deaf—such that they were unable to hear a shouted voice in their ear—to a moderate hearing loss, requiring only hearing aids as ongoing treatment, according to Auditory Insight's analysis of the preliminary data. "When I first saw these results, I felt more hope than I had in a long time for a pharmacological hearing loss solution," enthused Nancy M. Williams, president of Auditory Insight. "This was both a professional and personal milestone for me." She has advised gene therapy companies on surgeon, audiologist, and patient needs for gene therapy and genetic testing. Williams' work at Auditory Insight has tremendous personal meaning since she has a lifelong genetic, progressive hearing loss. Auditory Insight's latest research note provides an independent, rigorous analysis of published audiograms and other data from investigational clinical trials for gene therapy addressing otoferlin mutations. Three companies lead these trials: Eli Lilly's Akouos unit, Regeneron (who acquired Decibel Therapeutics), and China's Refreshgene Therapeutics. In a surgical procedure, the surgeon injects working copies of the gene into the patient's inner ear, where these transgenes create missing otoferlin proteins, a necessary ingredient in the complicated recipe for hearing. The research note highlights three important conclusions: Target Population. The gene therapy partially restored hearing for children aged less than one year to 11 years. Efficacy. The trials have restored patients' hearing in treated ears from profoundly deaf to moderate hearing loss. Time to Results. Patients' hearing showed improvement at four weeks and continued to notch up gains at the six-month mark. "Clinicians leading the trials have stated that they will continue to follow up with patients to determine the full length of time needed for the gene to express itself in improved hearing," Williams explains. For the estimated 200,000 people worldwide with otoferlin mutations, these clinical trial results offer optimism for those who seek restored hearing. The trials also matter because they advance the learnings of scientists developing gene therapy for other forms of genetic hearing loss. Williams is available to discuss this research and implications for gene therapy companies targeting hearing loss. About Auditory Insight Auditory Insight partners with senior leaders of hearing health pharmaceutical and device companies to create successful market development strategies. The firm also advises growth equity and private equity funds on creating portfolio value in hearing healthcare. SOURCE Auditory Insight LLC

The FDA's planned advisory committee meeting for Carvykti, AstraZeneca's approval in Japan, and Samsung Biologics' business growth made our news this week. The FDA will convene an advisory committee to discuss Johnson & Johnson and Legend's Carvykti filing in earlier multiple myeloma. AstraZeneca has won a world-first approval for its rare blood disorder add-on therapy in Japan. Samsung Biologics tallied an “exceptional” year in 2023. And more. 1. J&J, Legend's Carvykti bid for earlier multiple myeloma use will face FDA adcomm Johnson & Johnson and Legend Biotech’s application for Carvykti for earlier treatment of multiple myeloma will have to endure an FDA advisory committee meeting. Bristol Myers Squibb previously announced that the company’s rival CAR-T therapy, Abecma, will also face such a meeting. The FDA reviews come as the agency pushes for a new boxed warning outlining the risk of patients developing secondary T-cell cancers following the treatment of existing CAR-T therapies. 2. AstraZeneca adds to rare blood disease portfolio with world-first Voydeya approval in Japan AstraZeneca’s oral factor D inhibitor, danicopan, has won its world-first approval in Japan. Now branded as Voydeya, the drug is approved by Japanese authorities for use alongside a C5 inhibitor such as AZ’s Ultomiris to treat paroxysmal nocturnal hemoglobinuria patients who’ve had an inadequate response to a C5 inhibitor. 3. With record year, Samsung Biologics bucks CDMO industry's troublesome 2023 Samsung Biologics touted what it called an “exceptional” performance in 2023 despite an industrywide slowdown. In the fourth quarter, the Korean CDMO grew sales by 11% to 1.07 trillion Korean won ($802 million), pushing the full-year growth rate to 23.1%. Further, the company amassed contracts worth over $12 billion through expanded partnerships with 14 of the top 20 global pharma companies. 4. Samsung allotting ‘significant investment’ to bring noninvasive glucose sensor to wearables: Bloomberg Meanwhile, Samsung Electronics is working on noninvasive blood sugar monitoring for its Galaxy family of consumer devices, Hon Pak, M.D., head of the company’s digital health division, said. Samsung’s rival, Apple, is also trying to achieve a breakthrough in the same field. Pak also talked about the possibility of adding continuous cuffless blood pressure monitoring to Samsung’s wearables.   5. Glenmark bags subcutaneous checkpoint inhibitor, moving to turf targeted by Big Pharma Glenmark has picked up some regional rights to 3D Medicines and Jiangsu Alphamab Biopharmacueticals’ subcutaneous anti-PD-L1 antibody envafolimab. With a Chinese nod in 2021, the drug became the first subcutaneous checkpoint inhibitor approved anywhere. Glenmark is paying “low double-digit millions” for rights to sell the drug in India, Asia Pacific, the Middle East, Latin America, Africa, Russia and other places. 6. Gene therapy with dual viral vector restores hearing in children with hereditary deafness (release) A new study in China showed that a gene therapy restored hearing in five of six children with a form of deafness caused by mutations of the OTOF gene. The children showed a 40 to 57 decibel reduction in the auditory brainstem response testing after 26 weeks, according to results published in The Lancet. The therapy belongs to Refreshgene Therapeutics in Shanghai, and it utilizes a dual-AAV viral vector to deliver a functional OTOF gene. Other News of Note: 7. WuXi XDC, hot off $520M IPO, inks antibody-drug conjugate deal with Celltrion 8. Saudi Arabia launches plan to become biotech hub by 2040 9. Apotex, Heritage and Breckenridge settle with purchasers in generics price-fixing case