The Hearing System And Its Disorders 

Conductive hearing loss involves the mechanic portion

When the sound reaches the ear canal, it strikes the eardrum, causing its vibration. Behind the eardrum, a chain of 3 tiny bones, the ossicles, transmit the movement to the fluid that fills the cochlea. Problems to this portion of the hearing system prevent sound from flowing correctly. Today, medical devices provide a logical solution to treat the condition.

• Hearing aids, middle ear implants (MEI), and Bone-anchored hearing aids (BAHA) are the existing alternatives.

Sensorineural hearing loss involves the hair cells

The ossicles cause the fluid into the cochlea to move. The movement of the fluid is captured by tiny structures, called hair cells, which in turn activate the auditory nerve. Missing or damaged hair cells are the cause of sensorineural hearing loss (SNHL). As of today, medical devices are the best therapy.

• Cochlear implants and hearing aids are the most common solutions.
• 90% of hearing loss cases are classified as sensorineural.

Neural hearing loss involves the auditory nerve

The auditory nerve is responsible for sending the electrical signal to the brain. The brain interprets the message as sound. The absence or damage of the auditory nerve causes neural hearing loss. Currently, only one medical device has been developed to target the condition.

• The problem is usually treated with an Auditory Brainsteam Implant (ABI).

Medical Devices Give Way To Medicines

Hearing aids

Hearing aids improve the ability to hear by amplifying the volume of the sound. The devices are usually expensive, and most insurance providers don't cover the cost. Starting this year, lower-cost over-the-counter hearing aids are available for people with mild to moderate hearing loss.

• The global market is expected to grow by 4% CAGR over the next five years.
• Sonova has a 31% market share, Demant 30%, Sivantos 19%, GN ReSound 15%.

Cochlear implants

Cochlear implants are surgically implanted devices that partially restore the sense of hearing of people with moderate to severe sensorineural hearing loss. Implants bypass the damaged hair cells to deliver electrical signals directly to the nerve. Given the invasiveness and the poor quality of sound, their adoption has never taken off.

• The global market is expected to grow by ~1% CAGR over the next five years.
• Australian’s Cochlear dominates the industry with more than 60% of the global market, followed by Demant and Med-El.

A cure for sensorineural hearing loss

A less intrusive solution would make the two above devices obsolete and revolutionize the market. Regenerative medicine, designed for sensorineural hearing loss, has the potential to replace damaged or missing hearing cells.

• When hearing cells are damaged, they cannot grow back. With regenerative medicine, hearing cells regrow, and hearing loss reversed.

Disruptive Treatments On The Horizon

Congenital hearing loss

Gene therapy is under investigation to treat congenital hearing loss, caused by DNA changes that result in the production of atypical proteins. The treatment works by delivering a healthy piece of DNA into the hearing cells, enabling them to produce the functional protein and restore hearing.

• 32mn children have hearing loss; 50-60% of cases have genetic roots.
• Decibel Therapeutics and Akouos’ programs (respectively DB-OTO and AK-OTOF) are in the preclinical stage of development.

Deafness due to chemotherapy

Toxicity of chemo and radiation therapies can cause damage in the inner ear, leading to hearing loss. Researchers are developing treatments to protect hearing cells from the toxic effects of cancer drugs.

• After treatment with cisplatin, a widely used chemotherapeutic drug, 80% of adults and 50% of children have permanent hearing loss.
• Decibel Therapeutics’ candidate, DB-20, is in phase 1b trial to prevent hearing damage in people receiving cisplatin chemotherapy.

Degenerative hearing loss

Scientists are conducting clinical trials to evaluate whether regenerative approaches, which include the use of gene therapy or the activation of progenitor cells, are a viable solution to stimulate the regrowth of damaged hair cells, and thus cure sensorineural hearing loss (SNHL).

• SNHL accounts for 90% of all hearing loss.
• Frequency Therapeutics’ leading candidate, FX-322, and Audion Therapeutics’ compound LY3056480, are in phase 2.

Frequency Therapeutics Leads The Race

Unlocking the regenerative power of the ear

Progenitor cells are human cells found in vivo that hold the potential to regenerate tissues. In the hearing system, these cells are dormant. Frequency Therapeutics is developing a small molecule, FX-322, that hopes to wake them up.

• The compound is injected in the form of gel into the middle ear, overcoming the critical challenges of stem cell transplantation, i.e., delivery and integration.
• FX-322 enables regeneration without the development and manufacturing complexity of gene therapy.

Frequency therapeutics is playing it loud

FX-322 is rapidly advancing through a phase1/phase2 study. Results already showed encouraging signs of efficacy. In October 2019, the company started a phase 2a clinical trial, with top-line data expected in 2H20.

• Patients experienced a meaningful improvement in word recognition, sound clarity, and no serious adverse effects.
• The company has a partnership (for non-U.S. markets) with Astellas Pharma.

The next-generation regenerative company

As progenitor cells can be found all over the body, the approach has broader applicability. The company continues to target severe unmet conditions, which usually lead to faster pathways to market

• The next most advanced program is evaluating the progenitor cell approach for multiple sclerosis, which has an Investigational New Drug (IND) expected to be filed in 2H21, that would grant permission to start human clinical trials.
• In 2019, the FDA granted a Fast Track designation for FX-322.

Catalysts

• Positive results. This year, the results of some promising clinical trials (e.g., Frequency Therapeutics’ leading compound FX-322) have the potential to validate innovative approaches for hearing loss.
• M&A and collaborations. Companies target different types of hearing loss through different approaches. M&A and partnerships could expand the market reach and strengthen expertise.
• New fast track designations. Companies in this field are likely to be eligible for a fast track designation. The pathway, granted by the FDA, demonstrates the urgent need to find a cure for hearing loss.

Risks

• Trials failure. Any failure in ongoing clinical and preclinical trials could instill a sense of distrust in innovative approaches or could lead to mistrust in innovation approaches.
• Hearing Devices Advancements. If cochlear implants and hearing devices manage to reduce their prices, shrink in size, and overcome technical limitations, they may place themselves as valid competitors to novel treatments.
• Pricing. Innovative treatments are usually costly, and without reimbursement, patients may not be able to afford them.