Taking on the Challenge of Untreatable Conditions: Toward a “Future of Hearing” Through Drug Discovery

As the world ages, over 1.5 billion people are estimated to be affected by hearing loss. Often overlooked because it is hard to recognize, hearing loss has been increasingly acknowledged as a serious social issue linked to risks such as dementia and social isolation. However, there remain no effective drug treatments. Shionogi has launched a joint research program with Cilcare (France) to address this challenge through drug discovery.

This article introduces Shionogi’s first steps into the new frontier of hearing loss and the strong determination of researchers who want to develop a treatment.

Q: Mr. Kato, could you explain what hearing loss is?

Kato: Today, approximately 1.5 billion people worldwide are said to have some form of hearing impairment (2019). With aging populations and changes in lifestyle, it is projected that one in four people globally will experience hearing impairment by 2050. Because hearing ability declines gradually, it can be difficult to notice, leading to delayed detection. Unlike eyeglasses, hearing aids require months of careful adjustment to suit each individual, and owing to the inconvenience and stigma, many people choose not to use them.

Q: Is the problem of hearing loss limited to difficulty hearing?

Kato: Hearing loss is not just about difficulty hearing. It carries many risks for physical and mental health. Communication with others becomes difficult, which can lead to social isolation and, on a broader scale, significant losses for society as a whole. Reports estimate the global economic cost at approximately 1 trillion dollars annually.

For older adults, hearing loss is considered as a risk factors for dementia. Growing evidence suggest that improving hearing could help reduce dementia risk, making future research in this area highly anticipated.

Q: What causes age-related hearing difficulties, and what treatment options exist?

Kato: Hearing ability begins to decline gradually from our 30s and 40s. For example, the very high-frequency “mosquito sound” is only audible to young people. After the age of 65 years, the number of people experiencing hearing difficulties increases greatly, making it a pressing social issue.

At present, there are no effective drugs. The main options are symptomatic treatments such as hearing aids. This makes hearing loss one of the conditions with the highest “unmet medical needs.” Recognizing hearing loss as a “QOL disease with high social impact,” Shionogi decided to pursue drug discovery in this area.

Q: Shionogi is often recognized for its strengths in infectious diseases. Was venturing into hearing a major challenge?

Kato: Yes, this is Shionogi’s first foray into drug discovery in hearing loss; thus, we had to start from scratch in figuring out how to evaluate hearing. Consequently, we partnered with Cilcare, a biotechnology company specializing in auditory science. Cilcare is one of the world’s leading biotechnology company, with strong expertise in preclinical research and clinical development for hearing loss.

Q: What kind of drug are you aiming to develop in collaboration with Cilcare?

Kato: In some types of hearing loss, people can hear sound volume but still struggle to understand speech, making conversation difficult. Cilcare hypothesized that this may be due to damage in neural pathways that transmit sound to the brain. Based on this, they developed “CIL001,” a novel drug candidate designed to protect auditory nerves.

CIL001, now in development, protects auditory nerves and promotes the reconnection of synapses. By directly injecting the drug into the middle ear, it can precisely target the inner ear and minimize systemic side effects. In preclinical trials, results have shown improvements in auditory brainstem response (ABR) and increases in synapse counts.

Q: This is a very different approach from oral medicine. What challenges have you faced in drug discovery for hearing loss?

Kato: The ear itself is a complex sensory organ. The inner ear is a small, intricate structure encased in bone, and simply understanding its structure took considerable time. Additionally, hearing loss is difficult to measure because its symptoms are invisible and evaluation metrics are extremely delicate. We recognized that building a foundation entirely in-house would be difficult; thus, we began adopting external expertise, incorporating technologies like ABR measurement and inner ear tissue analysis. By visiting Cilcare’s labs and learning directly from their researchers, we are steadily building the capabilities needed for drug discovery.

Q: Is “CIL001” the only compound under development?

Kato: Actually, Shionogi is also pursuing its own original drug discovery. Our strength lies in manufacturing excellence, and we are aiming for “better compounds.” Combining Cilcare’s deep expertise in hearing loss with Shionogi’s drug discovery capabilities, teams across both companies are working together with a shared vision.

Q: How did Shionogi’s work in hearing loss drug discovery begin?

Kato: Drug discovery always begins with identifying patient needs. Beyond infectious diseases, we looked for areas where Shionogi’s strengths could be applied to unmet social needs; thus, hearing loss was selected. A major factor in this choice was the launch of the Communication Barrier-Free Project within our company. At this point, I’ll hand you over to Ms. Noguchi, one of the founding members.

Q: Ms. Noguchi, what is the Communication Barrier-Free Project?

Noguchi: The project was created to raise awareness of communication barriers caused by hearing difficulties and to help remove them. Hearing impairment symptoms vary widely. Some people cannot hear high-pitched sounds; others only perceive sounds vaguely. Despite this, the realities of hearing impairment are not well known, so people often shout at us in “loud voices.” As someone with congenital hearing impairment, I have been startled by people suddenly shouting into my ear.

Q: So not all people with hearing impairment need louder voices. Could you tell us more about the challenges you have encountered?

Noguchi: I often rely on lip-reading and sometimes use real-time transcription apps at work. However, there are difficulties, for example, during PC training sessions. Instructors look only at the screen and say things like, “Click here,” while quickly moving through steps. I couldn’t follow, and colleagues assumed I was slow to understand.

The problem is not ability, but communication. “Hearing difficulties” are often invisible, so necessary accommodations are overlooked. This is especially critical in healthcare settings, where many providers wear masks, making communication even harder. There have been cases where patients did not fully understand medication instructions, leading to reduced treatment effectiveness.

There are about 20 million people in Japan with hearing difficulties, yet communication barriers in healthcare are still poorly recognized. I strongly felt this had to change.

Q: Even good medicines will not work if patients do not use them properly. What actions have you taken?

Noguchi: We created a comic book explaining the challenges of hearing loss and crowdfunded its distribution to medical universities. The comic was so well received that it has even been introduced as teaching material at all medical schools in the UK.

Q: Through this project, did awareness of hearing difficulties also inspire drug discovery?

Kato: Currently, there are no drug treatment options for hearing loss, and even diagnostic approaches are limited. If we can create a medicine that alleviates hearing difficulties, we can work with physicians to establish new diagnostic and treatment guidelines, giving patients new options.

Q: Finally, could you share your vision for the future?

Kato: Hearing loss progresses gradually, making it difficult to notice. If treatment begins early, before the condition worsens, outcomes can improve. Therefore, we believe it is our mission to continue raising awareness about the importance of early detection and early treatment of hearing impairment.

If realized, this medicine could bring hope to patients suffering from hearing loss, at a global level, and greatly improve their quality of life. However, drug development is not the ultimate goal. What we truly aim for is a society where everyone can live authentically and vibrantly. By developing new medicines and creating a “future of hearing” for patients and their families, we want to contribute to healthier, richer lives. Through drug discovery and barrier-free communication activities, Shionogi will continue to meet society’s medical needs.

Shionogi is proud to sponsor the 25th Summer Deaflympics, Tokyo 2025.