Hearing Healthcare 2020 is a column where we explore the forces behind the changing landscape and disruptions impacting the hearing healthcare industry. While much of the recent discussions surrounding disruption in hearing healthcare and the broader hearing industry have been focused on issues like OTC and self-fitting hearing aids, very little attention has been focused on the potential impact of the biotechnology and pharmaceutical sectors over the coming decade–sectors that have seen a significant surge in hearing related R&D investment over the past few years.
This week, HHTM President and CEO, Kevin Liebe, interviews Dr. Carl LeBel, Chief Development Officer at Frequency Therapeutics, to discuss the company’s novel approach to treating sensorineural hearing loss. The company is currently in a Phase 2a clinical trial with its novel treatment, FX-322, which has shown significant promise in earlier trials, finding improvement in hearing thresholds and even a doubling of word recognition scores in some patients.
KL: Frequency Therapeutics seems to have one of the most promising approaches to treating sensorineural hearing loss. Would you please provide a brief explanation of what FX-322 is and how it could potentially treat hearing loss?
CL: I think in order to understand FX-322, we first need to understand the problem we’re tackling. As you may know, hearing loss frequently occurs when hair cells in the cochlea are damaged or destroyed – and this can happen through exposure to excessive noise, aging, viral or bacterial infection, or exposure to certain medications that are toxic to hair cells. Once these sensory hair cells are damaged in humans, they do not regenerate (as they do in other species). Loss of these cells is linked to permanent hearing loss.
FX-322 is a combination of two proprietary small molecule drugs, locally delivered to the ear, that are designed to work together to activate dormant progenitor cells in the cochlea in the inner ear (a progenitor cell is a stem cell that is pre-programmed for a specific activity – in this case to grow sensory hair cells).
In a Phase 1/2, double blind, placebo-controlled safety study, multiple patients with moderate to moderately-severe hearing loss, showed statistically significant improvements in key measures of clarity – including four patients who showed a doubling in their word recognition scores – establishing a hearing “signal” that may suggest the return of some hearing in these patients. Improvements in pure tones scores were also seen in certain patients at higher frequencies, including 10dB improvements at 8000Hz. This was the first time that data of this type has been shown.
With the increase in environmental noise, we believe these measures of clarity are critical. While hearing devices that help increase volume are the standard of care for hearing loss patients, we believe the clinical need for healthy hearing is around intelligibility – the ability to tune, filter, and clearly understand speech and sounds. Improving word and sound recognition, particularly in a noisy environment, could be incredibly meaningful to patients.
KL: What stage of development is FX-322 in today?
CL: We are currently evaluating FX-322 in a Phase 2a clinical trial. Phase 2a studies are conducted to help understand dose, schedule of dose, patient population and endpoints – the key components to be able to characterize if a drug works, the potential population for the drug and the magnitude of clinical benefit that is demonstrated.
Like the Phase 1/2 study, the Phase 2a is a double-blind, placebo-controlled trial and patients already have been diagnosed with hearing loss that is considered stable. This is key, as it is believed that once hearing loss is stable, it does not recover. For each patient we know exactly how much deficit they have in their hearing function when they come into our study.
Study participants will be treated for one month and monitored for outcomes based on the endpoints for an additional six months after treatment. We carefully selected each of these components in our trial design to help us understand not only how FX-322 works and but also to what extent we observe hearing improvement in patients treated with the drug.
We plan to report top-line data from this Phase 2a study in the second half of 2020. Our hope is that with these data, we will further demonstrate the hearing signal we saw in the Phase 1/2 study, better define the potential of the product and inform next steps. We are also looking at tinnitus and quality of life measures – and because our in our Phase 1/2 study we saw pure tone improvements in higher frequencies, we are measuring patient hearing up to 16 kHz (standard hearing tests are usually up to 8 kHz). This is important because hearing loss typically starts at high frequencies – and a lot of our ability to understand words relies on our ability to hear at those higher frequencies.
KL: How long does it take for a novel treatment, like FX-322, to become approved by the FDA and other regulatory agencies?
CL: Drug development is always a multi-year process. We can’t say exactly how long it will take. We are in our second clinical trial in the U.S. and on the basis of the results of this trial we will better define the path forward. But what I can say is that we are incredibly excited about the potential of FX-322 and we hope to explore that potential as quickly and responsibly as we can.
KL: Let’s say in the future that FX-322 receives all the necessary regulatory approvals to treat hearing loss, how do you envision the patient journey from diagnosis to treatment?
CL: This is an important question and an area where we are spending a lot of time working to understand. We certainly believe that both ENTs and audiologists will play an ongoing and critical role throughout the journey, but there is a lot we will need to learn about the profile of FX-322 before we can answer this with certainty.
KL: Five or ten years ago, it seemed there were not many companies or researchers invested heavily in this area. Why are we seeing so many startups and pharmaceutical companies becoming involved in treating hearing loss?
CL: This is an incredibly exciting time in the hearing space with substantial progress in the understanding of the underlying biology – and now the science to address that underlying biology is catching up.
At the same time, as we have this growing body of research around hearing loss, hearing loss has become an epidemic. There is now an increased awareness of the magnitude of hearing loss and the potential impact not only on quality of life but also on society. Hearing loss has been shown to have significant comorbidities such as depression, dementia and cognitive decline. With increased exposure to environmental factors, hearing loss is no longer a condition that primarily impacts aging populations and has increasingly become a condition impacting younger people. It’s truly a global phenomenon and unfortunately growing – and there are currently no approved therapies to restore hearing function.
Today, after decades of research, we have a better understanding of the relationship between the pathology of hearing and the resulting hearing loss. For example, in sensorineural hearing loss (SNHL), we know subjects with SNHL have lost a significant amount of their sensory hair cells. With that in mind, we made the connection between what we believe FX-322 does – activating progenitors, and cell division leading to the formation of new sensory hair cells– to that underlying biology resulting in patient hearing loss.
This is a unique approach in the field. Some organizations have been attempting to use gene therapy approaches, while others are using single molecules; those programs use an approach called trans-differentiation: essentially making a progenitor cell turn into a hair cell. That’s not the way nature intended for it occur.
KL: Whether it’s a pharmaceutical, gene therapy based, or some other approach, do you believe we will have an FDA approved therapeutic treatment option for sensorineural hearing loss in the next 5 years? Why or why not?
CL: It’s my belief that within this decade you will be looking for the first therapeutic for hearing loss to be approved. Who it works for, how it works, and the magnitude of improvement remains to be seen – but that is what we are working toward.
KL: Frequency recently had a successful IPO and raised over $80M. How will this additional funding help accelerate development of FX-322 and does it give your team a competitive advantage over other startups in this space?
The IPO gave us additional resources to help advance our hearing program and was also validation that others think we have a promising technology and approach. In addition, we were able to form an important partnership with Astellas Pharma that provided additional resources, and deep, global clinical development and commercial expertise with a shared focus in pursuing novel regenerative medicines in the ENT space.
SNHL impacts 90 percent of all people with hearing loss and this funding helps us laser focus on trying to bring to market the first therapeutic for SNHL as quickly as possible.
KL: Dr. LeBel, thanks for sharing your views with us today and providing us with an update on the progress Frequency is making towards developing a treatment for sensorineural hearing loss.
CL: Thank you for the opportunity to discuss FX-322 and our approach to developing a therapy for the treatment SNHL. We are excited about the year ahead and the potential to help the millions of people suffering from hearing loss
Carl LeBel, PhD, is the Chief Development Officer at Frequency Therapeutics, where he is leading clinical development of FX-322, Frequency’s potential product candidate for the treatment of sensorineural hearing loss. Before joining Frequency, Dr. LeBel served as Chief Scientific Officer at Otonomy Inc., and prior to that spent 14 years working in senior R&D leadership positions at Amgen. He is a scientific fellow of the American Academy of Otolaryngology, and a full member of both the American Association for the Advancement of Science and the Society of Toxicology. Dr. LeBel received his B.S. in Chemistry from the University of Detroit and his Ph.D. in Biomedical Sciences/Toxicology from Northeastern University. Dr. LeBel is also a co-inventor on numerous patents in the field of drug delivery for otology-related disorders.
Kevin Liebe, AuD, is President and CEO of the HHTM Group, which publishes Hearing Health & Technology Matters and FindHearing.com. He is also the co-founder of Audiology Exclusive, which helps audiology, ENT and hearing aid practices remain competitive through special savings on clinical products and services. As an audiologist, Kevin has experience in variety of settings, including private practice, ENT, and industry. He is a past president and board member of the Washington State Academy of Audiology.