New Delhi: In a medical breakthrough, a US-based pharmaceutical company, Regeneron, received regulatory approval on 23 April for Otarmeni, the world’s first gene therapy for genetic hearing loss. The drug, administered as a surgical injection to the ear, was found to restore hearing in 80 per cent of participants suffering from hearing loss caused by mutations in the otoferlin (OTOF) gene.
“The FDA approval of Otarmeni signals a new era in the treatment of genetic forms of hearing loss, where reinstating 24/7 natural hearing is now possible,” said A. Eliot Shearer, otolaryngologist at the Boston Children’s Hospital and one of the investigators of the trial, in a press release by Regeneron. “I’ve witnessed my trial participant responding to their mother’s voice, dancing to music and interacting with the world, and these moments are now possible for more children born with this hearing loss.”
Around 2-8 per cent of all genetic hearing loss cases worldwide, affecting nearly 2,00,000 people, are OTOF-related. This gene makes a protein called otoferlin, which helps the inner ear to transfer sound signals to the hearing nerve. When the protein is mutated or missing, the ear may still be able to detect sound, but the signal isn’t sent to the brain. So, the person is unable to hear clearly.
To restore hearing, Otarmeni delivers the OTOF gene into the inner ear through a surgical injection, using adeno-associated virus (AAV) therapy. First, the otoferlin protein is split into two AAV capsids, which are then spliced together to form the protein. This is also known as the double-AAV process. The non-pathogenic virus then acts as a vector to carry the gene to the necessary place.
“This is the first evidence that gene therapy has restored a sense of hearing to normal levels in previously impaired individuals. That is a huge step for the medical field,” Dr Srujan Kumar, a scientist at the Centre for Stem Cell Research in Christian Medical College (CMC) Vellore, told ThePrint.
This is the world’s first gene therapy drug for hearing loss, and Regeneron plans to make it free of cost in the US. But even as other global companies like Eli Lilly and Sensorion are working on gene therapies for hearing loss, India has a different challenge — it has to first establish infrastructure to test and identify hearing loss patients, and determine those who can benefit from gene therapy.
Hearing loss cases in India
Over 63 million people in India, many of whom are children under 14, suffer from hearing loss. India’s incidence of congenital (from birth) hearing loss is also double the global average — four to six cases per 1,000 live births. According to conservative estimates, nearly 50-60 per cent of all congenital hearing loss cases are related to genetics.
The OTOF gene is one of the causes, said Dr Alok Aggarwal, Chairperson, ENT, Sir Gangaram Hospital.
“Hearing loss is of two types – cochlear and retrocochlear. In cochlear loss, the issue is with the outer hair cells or in the cochlea, for which the only solution is cochlear implants,” he explained. “But for the other type of hearing loss, maybe OTOF-related, the cochlea is preserved, and the issue is in neurotransmitters, so gene therapy can also work.”
Like OTOF, other genes are responsible for hearing loss in patients — for example, a majority of cases in India are due to the GJB2 gene (responsible for hearing and skin maintenance). There have been studies linking the prevalence of genetic hearing loss cases in India to factors like consanguineous marriages—unions between blood relatives—in certain regions.
Such genetic cases are discovered through DNA sequencing and tests that can classify which genetic mutation is responsible for hearing loss.
“It is important to emphasise that genetic testing is not the first step; screening is. A large proportion of children with congenital hearing loss in India are still diagnosed late,” said Shaiket Deb, Director, Rare Disease and Reproductive Health at Strand Life Sciences, Bengaluru. “So universal newborn hearing screening must be the primary focus.”
Both cochlear implants and gene therapy, like Otarmeni, work well when they’re administered at the right time – during infancy and early childhood. Delayed diagnosis and therapies can impact the speech development of children, too.
“When children have hearing loss from birth, they don’t just lose one sense – they also often lose the ability to develop speech. Unlike hearing and seeing, speech is an acquired skill which comes from hearing,” said Dr. Kamran Asif, Associate Professor, Paediatric ENT, CMC Vellore. “If a child can’t hear, they can’t speak. So to avoid this neuroplasticity, we need to ensure hearing loss is detected as early as possible.”
In India, there is no nationwide mandatory screening programme for newborns. While some states like Karnataka, Tamil Nadu, and even Maharashtra have their own programmes, the country still has less than 20 per cent universal newborn hearing screening (UNHS) coverage, compared to 85-97 per cent in the US, UK, and Europe.
Also read: Tango partners’ brains sync up, new study finds. What it could mean for human communication
Genetic testing in India
Before India can focus on developing targeted gene therapies for hearing loss, it first needs to identify the genetic burden of the impairment in its population. As ENT specialists and genetic scientists explain, India is still expanding primary screening for hearing impairment in babies.
“Sometimes even parents don’t realise their child could have hearing impairment – in the early years, it is difficult to tell. So they wait too long to bring them to be screened,” said Dr Thomas V Paul, CMC, Vellore. “This means even if there’s a solution like cochlear implants, it is often administered late in some children.”
This is why doctors are still uncertain about the exact percentage of the population suffering from genetically induced hearing impairment.
How the screening works
Neonatal screening for hearing is usually done using an OAE (otoacoustic emissions) test, which sends small sound waves into the ear canal to record how the cochlea responds to them. Another, more comprehensive test is the Brainstem Evoked Response Audiometry (BERA) test, which verifies hearing loss through brainwaves.
But to determine whether the hearing loss is genetic or not, and identify which gene is causing it, patients need to undergo specific genetic tests. These can cost between Rs 8,000 and Rs 13,000, and an exome sequencing test for identifying the exact gene can cost up to Rs 40,000.
Deb points out that while India’s medical infrastructure is growing, genetic testing is still in its early stages and mainly concentrated in tier-1 cities. “So access is a major bottleneck,” said Deb.
Dr Thomas and Dr Asif added that even if the hearing-loss-causing genes were accurately identified, there needs to be proper research to see if they are even viable for gene therapy.
“Otoferlin is a single gene causing hearing loss, and the therapy is quite clean and smooth, too. That’s not always the case with other genes,” explained Thomas. “India’s gene therapy landscape needs to study other mutations more closely to develop other therapies.”
Also read: Genome India project reveals global databases are missing key Indian genetic variations
India’s gene therapy journey
Gene therapy is a targeted molecular technique that gained prominence in 1990, after a young girl in the US was treated for an immune disorder and became the world’s first gene therapy patient. Over the last few decades, the field has gone through its share of ups and downs, but recent developments have shown successful gene therapies for genetic disorders like blindness, muscular dystrophy, and sickle cell disease, and now even hearing loss.
India’s gene therapy journey, however, is a little different—still in early clinical stages. It is focused largely on blood disorders like haemophilia and thalassemia, and sickle cell disease.
“Gene therapy is a vast subject, and India is just getting started with its research. Before focusing on any area, we need to ask questions—how severe is the disease? How prevalent is it in the population? Is it amenable to respond to gene therapy?” said Thomas.
India has the second-largest global burden of sickle cell anemia, and over 4 per cent of India’s population is a carrier of β-thalassemia, which is an inherited blood disorder. Therefore, Indian researchers are largely focusing on these diseases for gene therapy.
So far, no indigenous gene therapy developed in India has received regulatory approval, but many institutions, led by CMC Vellore, are on the verge of it.
Other institutes like CSIR Institute of Genomics and Integrative Biology, Indian Institute of Technology Bombay and Biotechnology Research and Innovation Council – Institute for Stem Cell Science and Regenerative Medicine in Bengaluru are also conducting dedicated research in gene therapy. The Union government too launched the BioE3 Policy in 2024, which focuses on biotech research, including gene therapy.
In 2024, CMC Vellore—supported by the Department of Biotechnology of India—conducted India’s first successful human clinical trials for gene therapy for haemophilia A, which is a bleeding disorder connected to a deficiency in the factor VIII, which is a blood-clotting protein. A paper in the New England Journal of Medicine described how the trial, administered on five subjects, led to a zero annualised bleeding rate even six months after the therapy.
“CMC Vellore was the first institute to successfully conduct gene therapy for haemophilia not just in India, but in all of South Asia,” said Dr Thomas. “Our centre has been running for over 20 years, and we’ve achieved some big breakthroughs.”
In a similar vein, in 2025, Union Minister Jitendra Singh launched India’s first CRISPR-based gene therapy for sickle cell disease, developed at CSIR–Institute of Genomics and Integrative Biology (IGIB) in New Delhi, in partnership with The Serum Institute of India. Named BIRSA-101, this therapy is yet to begin clinical trials.
Neither the haemophilia therapy nor BIRSA-101 has received regulatory approval from the Central Drugs Standard Control Organisation (CDSCO), and it will be at least two to three years before either of these reaches the market. However, Dr Thomas and Dr Kumar of CMC Vellore, the bastion of India’s gene therapy journey, are confident that the country is moving on the right path.
“Given sufficient time, and with the existing scientific expertise, India is more than capable of developing cutting-edge gene therapies in the future,” said Dr Thomas.
(Edited by Janaki Pande)