Hearing Loss Treatment Report

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NLRP3 inhibitors such as Oridonin may provide new treatment strategy for noise-induced hearing loss

Some research that appeared on our radar recently: “Oridonin ameliorates noise-induced hearing loss by blocking NLRP3 – NEK7 mediated inflammasome activation” (March 23, 2021).

Link to the paper:

https://www.sciencedirect.com/science/article/pii/S1567576921002125

Excerpt:

Here, we further determined that treatment with oridonin could indeed interrupt the interaction between NLRP3 and NEK7 as well as inhibit the downstream inflammasome activation in mouse cochleae after noise exposure. Furthermore, we tested anakinra, another inflammatory inhibitor, and it was shown to partially alleviate the degree of hearing impairment in some frequencies in an NIHL mouse model. These discoveries suggest that inhibiting NLRP3 inflammasomes and the downstream signaling pathway may provide a new strategy for the clinical treatment of NIHL.

see it's simple toy story meme hearing loss oridoninWhat does that mean?

Here is an extremely loose – but simple – explanation of what this means:

  • inflammation is involved in noise-induced hearing loss (NIHL)
  • we aren’t sure how, exactly
  • but it seems that… sometimes… inflammation can go way too far
  • which might actually make things worse, or interfere with healing
  • this could be what happens in the ear after acoustic trauma
  • we aren’t sure about that either
  • but according to this theory…
  • maybe a drug that keeps the inflammation process from going way too far…
  • … might also help with the healing process and prevent further damage
  • (by making sure inflammation does not get carried away)
  • this might apply in the context of noise-induced hearing loss
  • Oridonin, anakinra are two drugs worth studying for this
  • but we aren’t sure… yet

Now, for those of you who prefer the nitty gritty details… diving deep into the science… and the technical side of things…

Here is some further reading about Oridonin – “a covalent NLRP3 inhibitor with strong anti-inflammasome activity” – from Nature:

https://www.nature.com/articles/s41467-018-04947-6

From that paper:

Oridonin (Ori) is the major active ingredient of the traditional Chinese medicinal herb Rabdosia rubescens and has anti-inflammatory activity, but the target of Ori remains unknown. NLRP3 is a central component of NLRP3 inflammasome and has been involved in a wide variety of chronic inflammation-driven human diseases.

Hmmm…

(I wonder if it has anything to do with osteoclasts…)

That’s all for now.

PS: I am finally finishing the setup for email updates. If you have already signed up for the newsletter… in the next few days you will (finally) be getting an email from newsleter@hearinglosstreatmentreport.com asking you to confirm your email address. First issue of the official Hearing Loss Treatment Report Newsletter is going to be a very special one… – Michael (author/admin)

Estimated PIPE-505 Phase 2a Study Completion Date: June 12, 2021

Short but sweet update:

We now have an estimated completion date for the PIPE-505 phase 2a clinical trial: June 12, 2021.

Details below:

  • The PIPE-505 study record was updated on March 29, 2021.
  • The study completion date was changed from March 2021 [Anticipated] to June 2021 [Anticipated].
  • The June 12, 2021 date [Estimated] was calculated using information found within the study record and its history of changes, including: a) the submission date on which the Study Status was changed from “Recruiting” to “Active, not recruiting” and, b) the maximum follow-up Time Frame (“3 months after drug administration”) as detailed in the Outcome Measures section.
  • For a more conservative completion date, replace the last submitted update to Study Status date with the more recent last submitted update date of March 26, 2021. This gives us June 24, 2021.
  • Taken together, we are looking at a range of June 12 – June 24, with June 12th as the one to mark on your calendar.

PIPE-505 phase 2 completion date

Source: History of Changes for Study: NCT04462198 (Phase I/IIa Study Evaluating Safety and Efficacy of an Intratympanic Dose of PIPE-505 in Subjects With Hearing Loss)

That’s all for now.

We will probably have the next PIPE-505 update for you before June 15th (and/or whenever Pipeline Therapeutics makes an announcement).

For ongoing PIPE-505 updates and news of other upcoming hearing loss treatments, sign up for the free once-weekly email newsletter.

Message from the author:

Hey, Michael here. Thanks for visiting and… feel free to email michael@urgentresearch.com and say hello, any time. Let me know what type of hearing restoration treatment updates you want. Or tell me which experimental treatments you’re following closely right now. Feedback is also welcome and reader questions are encouraged.

P.S. Small favor to ask. Do you know someone who might find the information on this website helpful or uplifting? If you do… would you send them a link? Here: https://www.hearinglosstreatmentreport.com/

Sincerely,
Michael

BREAKING: CGF166 Clinical Trial Results Posted Online…

CGF166 update: Results from the phase 1/2 study of the hearing loss drug are now available.

Developing story…

CGF166 has results clinical trial update

Two days ago, on March 30, 2021, the official study record of CGF166 was updated on ClinicalTrials.gov.

This update was not accompanied by a press release from Novartis nor any media coverage.

However, this “surprise” update had two important words: has results.

An unexpected update

These results came out of nowhere…

For anyone learning about CGF166 for the first time, here is some quick background info on the “mysterious” Novartis gene therapy drug candidate for hearing loss:

A Case Study: Using Regenerative Medicine to Treat Hearing Loss

In 1999, scientists singled out a gene called atonal as a “master switch” for turning on the growth of inner ear hair cells, which pick up sound waves and translate them into electrical signals in the brain. Humans are born with hair cells, but the atonal switch flips off at birth. Any subsequent damage to hair cells is permanent.

In collaboration with a biotech company, GenVec Inc, NIBR researchers have developed an experimental gene therapy called CGF166 to restore hearing function by regenerating hair cells. It consists of a viral vector carrying the atonal gene. The vector has been altered with the aim of making it harmless and is injected directly into the inner ear. CGF166 is now being tested in a limited number of patients with severe-to-profound hearing loss.

SOURCE: an old brochure from the Novartis Institute for Biological Research (NIBR), circa 2016.

Sounds promising, right?

Absolutely.

But that material was written 5 years ago and… since then – aside from the early buzz and media coverage on this holy grail treatment – CGF166 updates have been incredibly rare.

In fact, before today… the last credible update we got on CGF166 was from over a year ago when, on February 21, 2020, BioCentury pointed out that Novartis had “yet to publicly report data from its Phase I/II trial of gene therapy CGF166.”

SOURCE: Regenerative medicine for hearing loss makes quiet progress, BioCentury, https://www.biocentury.com/article/304491, dated February 21, 2020.

Well, now it looks like they (quietly) have.

The results were uploaded to the study record of the phase I/II clinical trial. Here is the official description:

The goal of the study was to evaluate the safety, tolerability, and the potential ability of CGF166 delivered through IL-infusion to improve hearing. CGF166 is a recombinant adenovirus 5 (Ad5) vector containing a cDNA encoding the human Atonal transcription factor (Hath1).

This study evaluated the safety, tolerability, and potential efficacy of CGF166 and the associated delivery procedures in patients with severe-to-profound unilateral or bilateral hearing loss. Eligible patients were required to have documented, non-fluctuating hearing loss.

SOURCE: https://clinicaltrials.gov/ct2/show/NCT02132130, last updated March 30, 2021.

CGF166 study results: Part 1

These results do not show all the data and numbers, but we expect to post a follow-up once we have some experts review them.

Here is the direct link to the study results that were uploaded on March 30, 2021: ClinicalTrials.gov Identifier: NCT02132130 – Study Results

It’s important to keep in mind that these results are NOT the same thing as an announcement or press release from the company. For that reason, there is no accompanying commentary or explanation of what these results mean.

CGF166 results sneak preview confusion emojiThis can be frustrating, but here at Hearing Loss Treatment Report we are currently working on a follow-up post that will provide a clear idea of what these numbers mean for people with hearing loss.

This is a developing story…

I wish we had more for you.

This is all we have, for now.

We will continue to monitor what is happening with CGF166 and post an update as soon as we know more. (The best way to get updates is by subscribing to our email newsletter – which we’ll be sending out very soon!)

cgf166 trial results meme

For now, we decided to share the link to these “raw” results because we believe in sharing early and sharing often. Information ASAP. Before the official press releases, before company Twitter announcements, before the media outlets, before before before.

And so, for that reason, we didn’t want to sit and wait on this long-awaited study result update just so we could organize it into a neatly-wrapped package with in-depth commentary.

That’s not our style.

“First”

The reason we believe in this post-first-question-later approach is because an increasingly large number of patients, organizations, and industry professionals use this site as a shortcut to the very latest hearing loss treatment updates.

Think of this site like a secret source of some of the fastest, earliest updates in the world of hearing loss drug development. And it’s meant to help inform people in situations like this: where this CGF166 phase I/II results story was missed, ignored, or simply too early (and thus unknown) to the mainstream media.

Which is also why you might want to subscribe to our email updates list… so you can get as-fast-as-we-can-find-them updates on experimental hearing restoration drugs and milestones… plus, sneak previews of what potential “cures” are really around the corner in 2021, 2022, and beyond…

But it’s not for everyone.

Questions? Comments? Corrections? Feedback:

Send an email to michael@urgentresearch.com and say hello.

HLAA to Hold Patient-Focused Drug Development Webinar for People and Families Living with Sensorineural Hearing Loss (April 8)

HLAA Webinar: Externally-Led Patient-Focused Drug Development Meeting for People and Families Living with Sensorineural Hearing Loss

hlaa-pfdd

This one-hour webinar will provide an overview of the FDA drug development process as well as the value of Patient-Focused Drug Development (PFDD) meetings. We hope this webinar will spike your interest in being part of this important virtual meeting for the hearing loss community taking place on Tuesday, May 25, 2021.

HLAA to Hold Patient-Focused Drug Development Webinar and Meeting

Externally-Led Patient-Focused Drug Development Meeting for People and Families Living with Sensorineural Hearing Loss

Frequency Therapeutics Releases New Data from Two FX-322 Clinical Studies

https://www.businesswire.com/news/home/20210323005208/en/Frequency-Therapeutics-Releases-New-Data-from-Two-FX-322-Clinical-Studies-Plans-to-Advance-Single-Dose-Regimen

Frequency Therapeutics Releases New Data from Two FX-322 Clinical Studies; Plans to Advance Single-Dose Regimen
Interim FX-322 Phase 2a Results Show Four Injection Schedule Had No Discernible Hearing Benefit

Separate FX-322 Phase 1b Study Confirms Hearing Improvement from Single Injection

Conference call at 8:30am ET today

VEGF-A165 restores vascular function to the inner ear and could potentially reverse common forms of hearing loss…

Could improving poor blood supply to the damaged inner ear reverse noise-induced and/or age-related hearing loss?

Yes, according to some fascinating new research from Zhang et al, published yesterday on March 9, 2021, that describes a unique approach to hearing restoration that is backed by “clear-cut evidence”…

VEGF-A165 article screenshot
This VEGF-A165 research paper is hot off the press!!!

Here is a link to a full-text PDF copy of the paper (and all the science-y details):

VEGF-A165 gene therapy ameliorates blood-labyrinth barrier breakdown and hearing loss [PDF]

Sneak preview of the abstract:

When hearing loss is caused by noise or aging, it is often associated with breakdown of the barrier between the cochlea and its blood vessels. Pericytes populate many small vessels in the adult inner ear, however, their role in different forms of hearing loss is largely unknown. Using an inducible and conditional pericyte depletion mouse model, we show that loss of pericytes leads to marked changes in vascular structure, resulting in poor blood circulation and hearing loss. In vitro, using advanced tissue explants from pericyte fluorescence reporter models in combination with exogenous donor pericytes, we show pericytes, signaled by endothelial growth factor isoform A165 (VEGF-A165), vigorously drives new vessel growth in both adult and neonatal mouse inner ear tissue. In vivo, the delivery of an adeno-associated virus serotype 1 (AAV1)-mediated VEGF-A165 viral vector to pericyte depleted animals regenerated lost pericytes, improved blood supply, reduced loss of sensory hair cells, and attenuated hearing loss. These studies provide the first clear-cut evidence that pericytes are critical for adult hearing and can regenerate cochlear vasculature. The restoration of vascular function in the damaged inner ear with AAV1-mediated VEGF-A165 gene therapy is a new strategy for ameliorating vascular associated hearing disorders, including common forms of age-related hearing loss.

SOURCE: Zhang et al. Published March 9, 2021. JCI Insight 2021. https://doi.org/10.1172/jci.insight.143285.

That’s all for now.

The Hearing Loss Treatment Report system will be monitoring the scientific literature and news for any further mentions of VEGF-A165… including any progress it makes toward that first big milestone: human clinical trials.

We don’t have a timeline for you (yet)… but you can expect some follow-up coverage in the coming weeks/months.

Stay tuned.

RE: how to get VEGF-A165 updates

To follow what’s happening with VEGF-A165 (as well as other treatments such as FX-322, OTO-413, PIPE-505), I encourage you to sign up for Hearing Loss Treatment Report email updates. These updates are 100% free… your information is kept private, and… you won’t get any spammy marketing emails or promotional emails. That’s a promise. Instead, you will only receive important (and often exclusive) updates related to up-and-coming hearing loss treatments and scientific breakthroughs.

Questions? Comments? Feedback?

Send an email to michael@urgentresearch.com and speak your mind.

I read every email and try my best to reply (thoughtfully) within 1-2 days.

P.S. Do you like these “exclusive” update posts?
Kindly share them with people you know who might find them interesting.

Research center at Creighton University awarded $10.8 million NIH grant to help researchers discover new drugs for hearing loss

https://www.newswise.com/articles/translational-hearing-center-awarded-largest-nih-grant-in-creighton-university-history

Translational Hearing Center awarded largest NIH grant in Creighton University history
NIH grant to help researchers translate basic hearing loss research into practical therapies

Research center at Creighton University awarded $10.8 million NIH grant to help researchers discover new drugs for hearing loss

Frequency Therapeutics Announces Publication of FX-322 Phase 1/2 Data Showing Hearing Improvements in Sensorineural Hearing Loss Patients

https://www.businesswire.com/news/home/20210222005818/en/Frequency-Therapeutics-Announces-Publication-of-Phase-12-Data-Showing-Hearing-Improvements-in-Acquired-Sensorineural-Hearing-Loss-Patients-Receiving-FX-322

Frequency Therapeutics Announces Publication of Phase 1/2 Data Showing Hearing Improvements in Acquired Sensorineural Hearing Loss Patients Receiving FX-322
Results Published in Leading Peer-Reviewed Otolaryngology Journal, Otology & Neurotology

Statistically Significant Improvements Observed in Word Recognition Tests in Quiet and in Noise; Suggests Potential to Improve Speech Intelligibility, a Major Unmet Need for Individuals with Hearing Loss

Company Expects Interim FX-322 Phase 2a Study Data Later this Quarter

https://journals.lww.com/otology-neurotology/Abstract/9000/Improved_Speech_Intelligibility_in_Subjects_With.95768.aspx

Sensorion Presents New Preclinical Data on SENS-401 at ARO 2021: significant treatment benefits in rats with severe hearing loss when initiated within 7 days of acoustic trauma

https://www.businesswire.com/news/home/20210218006082/en/Sensorion-Presents-New-Preclinical-Data-on-SENS-401-at-ARO-2021

Sensorion Presents New Preclinical Data on SENS-401 at ARO 2021
SENS-401 yields significant treatment benefits in rats with severe hearing loss when initiated with a delay up to 7 days after the initial acoustic trauma
Sensorion presenting three posters at Association for Research in Otolaryngology (ARO) meeting
ARO will be hosted virtually on February 20-24, 2021

OTO-413 Phase 1/2 trial expansion in hearing loss expected to start in Q2 2021 with results anticipated in mid-2022

https://www.globenewswire.com/news-release/2021/02/11/2174562/0/en/Otonomy-Reports-Fourth-Quarter-and-Full-Year-2020-Financial-Results-and-Provides-Corporate-Update.html

Otonomy Reports Fourth Quarter and Full Year 2020 Financial Results and Provides Corporate Update

February 11, 2021 16:17 ET | Source: Otonomy, Inc.
OTIVIDEX® Phase 3 trial results in Ménière’s disease expected by end of February
OTO-313 Phase 2 trial in tinnitus planned to start in first quarter of 2021 with top-line results expected in mid-2022
OTO-413 Phase 1/2 trial expansion in hearing loss expected to start in second quarter of 2021 with results anticipated in mid-2022

New pill [SPI-1005] that may help improve age-related hearing loss by protecting delicate hair cells in the inner ear

https://www.dailymail.co.uk/health/article-9238361/New-pill-help-hear-clearly-protecting-delicate-hair-cells-inner-ear.html

New pill that may help improve age-related hearing loss by protecting delicate hair cells in the inner ear
A new drug, SPI-1005, aids hearing by protecting delicate hair cells in inner ear
It is also being tested in U.S. as a potential treatment for patients with Covid-19
The number of auditory hair cells declines due to age, disease and loud noise

PREVIEW: “Preclinical/Clinical Translational Evidence for a Potential Hearing Restoration Therapeutic, FX-322” [ARO 2021 Podium Presentation]

Here is a sneak preview of an upcoming podium presentation from Will McLean (Frequency Therapeutics) about hearing restoration and FX-322:

FX-322 podium abstract for ARO February 2021

What’s happening:

In less than two weeks from today, the 44th Annual ARO MidWinter Meeting will begin.

It is a virtual conference.

On Monday, February 22, 2021, Will McLean (Frequency Therapeutics) will give a podium presentation at this virtual conference.

Topic? FX-322…

Here is a copy of McLean’s podium abstract:

Preclinical/Clinical Translational Evidence for a Potential Hearing Restoration Therapeutic, FX-322

Background: Cochlear hair cell loss in mammals is permanent because progenitor cells fail to divide and differentiate on their own. Previous work has shown that the two compounds in FX-322 enhance the regenerative potential of mouse and human progenitor cells in vitro. This multi-group collaboration assessed the pharmacodynamic (PD) and restorative potential of FX-322 in a mouse noise-induced hearing loss (NIHL) model, cochlear pharmacokinetics (PK) of intratympanically injected FX-322 in guinea pigs, perilymph concentrations in patients undergoing cochlear implantation, and a safety study of FX-322 in patients with permanent sensorineural hearing loss (SNHL).

Methods: PD effects were first assessed in a NIHL mouse model to assess the therapeutic potential of FX-322. PK studies with FX-322 were performed in guinea pigs to calibrate a well-established computer model predicting drug distribution over the length of the cochlea with time. The animal PK model was extended to humans by analysis of perilymph samples collected from subjects undergoing cochlear implant surgery. A double-blinded, placebo-controlled, safety trial in patients with permanent/stable SNHL was conducted to assess the systemic safety, plasma PK, and effects on otoscopy, audiometry, and word testing (WR, WIN). The trial enrolled 23 patients with medical histories consistent with either NIHL or sudden SNHL. Treatment was a single unilateral intratympanic dose and patients were monitored overnight for safety, PK and PD over a 90-day period.

Results: Animal PD – A single intratympanic injection of FX322 was associated with increased hair cell counts and improved auditory function compared to placebo in mice with NIHL within one month after treatment. Guinea Pig PK – FX-322 concentrations in samples taken from the RW niche were found to decrease with time, with elimination half-times under 1 hour. The highest drug concentration was observed in the basal regions. Human PK – Intraoperative middle ear contents and perilymph were analyzed for FX-322 approximately 1 hour into surgery for cochlear implant subjects (n=7). While some subjects had anatomical features that have been speculated to impair drug entry, such as mucosal folds or bony overhangs, FX-322 was quantified in all samples analyzed. Human Safety and PD – FX-322 was associated with a favorable safety profile. In FX-322-treated subject ears WR and WIN improved over the duration of the study while placebo-treated subject ears did not.

Conclusions: Both preclinical and clinical PK analyses suggest that FX-322 was able to achieve therapeutically active levels in the extended high frequency region of the cochlea. Preclinically, this was associated with an increase in hair cell counts and auditory brainstem response thresholds. The present work provides the first evidence that a novel potential therapeutic, FX-322, is associated with clinically meaningful improvements in speech recognition in subjects with permanent and stable SNHL, and larger clinical studies are underway.

The source of this “podium abstract” is the Association for Research in Otolaryngology (ARO)’s 44th Annual Mid-Winter Meeting event website.

Here is a link to the official PDF copy of the February 22, 2021 FX-322 podium presentation [EDIT #1: the link does not work, removed] (uploaded online by ARO’s event organizers… who have once again done a superb job organizing all of the presentations, speakers, podiums, posters, and more, into a friendly and searchable format *even when some links don’t work!).

What’s “new” here?

For readers who have been closely following FX-322 updates… there is nothing truly “new” in this presentation preview. However, we do not know what other data or information or announcements will be shared alongside this presentation. Perhaps we will also get a press release on Monday, February 22 which gives us more substantial “news” *fingers crossed*…

RE: FX-322 updates…

If you’re interested in news updates RE: the very latest hearing loss treatments and recent progress toward potential cures… remember to sign up for the HearingLossTreatmentReport.com email newsletter. It’s 100% free and the goal is to give you an easy (and fast) way to get updates about FX-322 and other promising hearing restoration therapeutics – earlier… often days (and sometimes weeks) ahead of “mainstream” sources.

Questions? Comments? Feedback? Send an email to michael@urgentresearch.com and say hello.

Frequency Therapeutics appoints Chief Manufacturing Officer as it prepares for larger studies in support of lead FX-322 program

https://investors.frequencytx.com/news-releases/news-release-details/frequency-therapeutics-appoints-quentin-mccubbin-phd-chief

Frequency Therapeutics Appoints Quentin McCubbin, Ph.D., as Chief Manufacturing Officer
WOBURN, Mass.–(BUSINESS WIRE)–Jan. 19, 2021– Frequency Therapeutics, Inc. (Nasdaq: FREQ), a clinical-stage biotechnology company focused on harnessing the body’s innate biology to repair or reverse damage caused by a broad range of degenerative diseases, today announced the appointment of Quentin McCubbin, Ph.D., as chief manufacturing officer. Dr. McCubbin will oversee Company technical operations, leading drug product formulation, chemistry manufacturing and controls (CMC) and supply chain, to support the development of Frequency’s pipeline of product candidates.

Dr. McCubbin joins Frequency from Cerevel Therapeutics, a clinical-stage biotechnology company where he served as head of technical operations. Prior to Cerevel, he spent 19 years at Takeda/Millennium Pharmaceuticals in various roles progressing in responsibility, including six years as vice president of pharmaceutical sciences and global head of process chemistry.

“Quentin’s background and leadership in technical operations will be critical as we prepare for larger studies in support of our lead FX-322 program that aims to treat the most common form of hearing loss, and as we look to diversify and expand our clinical pipeline with a program for remyelination in multiple sclerosis,” sa

Sensorion Provides Update on Development of SENS-401 for Sudden Sensorineural Hearing Loss: Phase 2 topline results delayed, now expected in Q4 2021…

https://www.businesswire.com/news/home/20210104005852/en/Sensorion-Provides-an-Update-on-Plans-and-Progress-in-the-Development-of-SENS-401-for-the-Prevention-of-Hearing-Loss

Sensorion Provides an Update on Plans and Progress in the Development of SENS-401 for the Prevention of Hearing Loss
Clinical trial to treat patients suffering from Cisplatin Induced Ototoxicity (CIO) with SENS-401 expected to start in H2 2021
Natural history study in CIO expected to start in H1 2021 to generate data on disease evolution

Phase 2 topline results from SENS-401 study in SSNHL delayed further due to COVID-19 and now expected in Q4 2021

Frequency Therapeutics to Host Investor Event on the Potential for Restorative Treatments for Acquired Sensorineural Hearing Loss

CATEGORY:
News, Companies, Press Releases

TAGS:
Frequency Therapeutics

TITLE:
Frequency Therapeutics to Host Investor Event on the Potential for Restorative Treatments for Acquired Sensorineural Hearing Loss

DESCRIPTION:
Event to be Held   January 19, 2021 at 8:00 am ET ; Will Feature Prominent Otolaryngology and Audiology Key Opinion Leaders Phase 2a Day-90 Readout for FX-322, Frequency’s Lead Product Candidate, for Acquired Sensorineural Hearing Loss Anticipated in Late Q1 2021; End of Study Readout in Late Q2

SOURCE:
Frequency Therapeutics

GUID:
aa0e5cd3eeeda8adba6fabfea4ff535c

ID:
b96d0a0b599e6d4315f064cd6ff0e099aa0e5cd3eeeda8adba6fabfea4ff535c

DATE – PUBLISHED:

DATE – FOUND:
12/18/20 08:22AM

LINK – PUBLISHER:
https://investors.frequencytx.com/news-releases/news-release-details/frequency-therapeutics-host-investor-event-potential-restorative/

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2020-12-18T13:22:17+00:00, https://www.hearinglosstreatmentreport.com.

Otonomy Reports Positive Top-Line Results from Phase 1/2 Clinical Trial of OTO-413 in Patients with Hearing Loss

https://investors.otonomy.com/news-releases/news-release-details/otonomy-reports-positive-top-line-results-phase-12-clinical-0

Otonomy Reports Positive Top-Line Results from Phase 1/2 Clinical Trial of OTO-413 in Patients with Hearing Loss
December 17, 2020 at 7:00 AM EST
OTO-413 demonstrated a higher proportion of responders than placebo based on multiple speech-in-noise hearing tests

Clinical Trial of FX-322 for Age-Related Hearing Loss Is Now ACTIVE

Study is no longer recruiting participants. 30 patients enrolled. Half will get a single dose of FX-322, other half will get a placebo. Estimated primary completion date: March 2021. Estimated study completion date: June 2021. Stay tuned…

Link to official study record (last update posted on December 16, 2020):

https://clinicaltrials.gov/ct2/show/NCT04601909

The other recently-added FX-322 study (for severe sensorineural hearing loss) is expected to start before the end of the year, according to a November 16 press release from Frequency Therapeutics.

More updates to follow. Remember to subscribe to the email newsletter, which will begin sending soon. Email michael@urgentresearch.com if you have any comments or feedback.

Sonova Invests €5 Million in Sensorion [SENS-401] as the Companies Plan a Collaboration in Hearing Loss

https://www.businesswire.com/news/home/20201214005892/en/Sonova-Invests-%E2%82%AC5-Million-in-Sensorion-as-the-Companies-Plan-a-Collaboration-in-Hearing-Loss

Sonova Invests €5 Million in Sensorion as the Companies Plan a Collaboration in Hearing Loss
Sonova invests at €1.70 per share, to hold circa 3.7% stake in Sensorion
Companies signed a letter of intent relating to a collaboration to develop new solutions for hearing loss

Upcoming Webinar from the Hearing Medicines Discovery Syndicate: “How and Why” to Commercialise your Hearing Research (Nov 26)

https://go.md.catapult.org.uk/how-why-commercialise-hearing-research/

The Emerging Hearing Medicines Landscape

A monthly webinar series developed by the Hearing Medicines Discovery Syndicate, exploring hearing drug discovery in the context of an emerging area for medicines development and a growing market.

Through this series of webinars, we will explore the emerging hearing medicines landscape by inviting leading clinicians, academics and industry representatives along with people with lived experience of hearing loss, to share their expertise and insight.

Over 4 webinars we will provide a 360-view of the field covering the patient need, the key challenges faced by innovators, how to commercialise your hearing research and why regenerative approaches could be a game-changer for hearing medicines discovery.

Frequency Therapeutics adds YET ANOTHER new FX-322 clinical trial… for SEVERE sensorineural hearing loss

Added today: A Phase 1b, Prospective, Randomized, Double-Blind, Placebo- Controlled, Single-Dose, Multicenter, Safety Study of FX-322 Administered by Intratympanic Injection in Adults With Severe Sensorineural Hearing Loss.

This is a Phase 1b placebo-controlled, double-blind, single-dose safety study of intratympanic FX-322 dosed in subjects with severe sensorineural hearing loss.

Approximately 30 subjects are planned to be enrolled in this study. The subjects will be randomized to receive one dose FX-322 (24) or placebo (6) and will return for safety, otologic, and audiologic assessments at Days 30 and 90 after the study injection.

What makes this new FX-322 trial different (compared to the trial that was added last month)?

This new study is for severe sensorineural hearing loss (previously added study is for age-related hearing loss). The inclusion criteria requires a “pure tone average of “26-70 dB at 500Hz, 1000Hz, 2000Hz, and 4000Hz at screening in the ear to be injected.”

Does it include a Tinnitus Assessment as a secondary outcome measure?

Yes.

Measured by the Tinnitus Functional Index (TFI), with a scale ranging from 0 to 100 that defines severity categories based on 25 self-reported answers.

What else? More fun facts:

Study is Recruiting and will enroll 30 participants. It does involve a placebo group however the ratio is 4:1 which means most (24) of the participants will get FX-322.

If you like those odds, here are the states where clinical trial sites are located:

  • Florida
  • Nebraska
  • New York
  • Texas
  • Virginia

Could more locations be added?

Very possible. We will post an update if/when more sites are added.

Here is the official link to the study:

https://clinicaltrials.gov/ct2/show/NCT04629664

More FX-322 updates:

If you want ALL of the FX-322 updates and exclusive hearing loss treatment-updates sign up for the free email newsletter.

Frequency Therapeutics Announces Expanded FX-322 Clinical Development Program and Upcoming Day-90 Phase 2a Analysis

https://investors.frequencytx.com/news-releases/news-release-details/frequency-therapeutics-announces-expanded-fx-322-clinical

Frequency Therapeutics Announces Expanded FX-322 Clinical Development Program and Upcoming Day-90 Phase 2a Analysis
Company Will Report Data from Phase 2a Sensorineural Hearing Loss (SNHL) Study in Late Q1 2021

First Patient Dosed in Phase 1b Study of Age-Related Hearing Loss; Additional Phase 1b Study for Severe SNHL Patients to Start This Quarter

SENS-401 Phase 2 trial results expected in mid-2021, prelinical data expected by end of 2020

https://www.businesswire.com/news/home/20201020006234/en/Sensorion-reports-2020-first-half-results

Preclinical data from these studies are expected by the end of 2020.

Sensorion reports 2020 first half results
Financial position strengthened with €31m (US$36.5m) capital raise in September 2020

Gene therapy agreement expands pipeline and preclinical data
SENS-401 Phase II trial progressing with results expected in mid-2021
Cash position of €30.7m as of June 30, 2020, further reinforced by September capital raise
Cash runway now extended to H2 2022

Estimated FX-322 Phase 2a Study Completion Date: May 21, 2021

Very quick update:

The FX-322 Phase 2a clinical trial is now *officially* active and we now have an updated estimated completion date for the study: May 21, 2021.

Details below:

  • The FX-322 study record was updated on October 8, 2020
  • The study status was changed from “Recruiting” to “Active, not recruiting”
  • The study completion date was changed from September 30, 2020 [Anticipated] to May 21, 2021 [Anticipated].

FX-322 trial update October 8, 2020 now active

Source: History of Changes for Study: NCT04120116 (FX-322 in Adults With Stable Sensorineural Hearing Loss)

That’s all for now.

For the latest FX-322 updates and news of other hearing loss treatments, sign up for the free once-weekly email newsletter.

Email michael@urgentresearch.com and say hello. Let me know what type of hearing loss treatment updates you like best. Feedback encouraged.

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How much will FX-322 cost? David Lucchino, Frequency Therapeutics CEO, talks pricing and value…

How much will FX-322 cost?

David Lucchino, CEO of Frequency Therapeutics, was recently asked for some “rough ideas around [the] pricing and reimbursement” of FX-322.

Here is a lightly edited* almost-word-for-word transcript of David’s response**:

*EDITED HOW? Disconnected parts of speech and filler words such as umm, well, you know, etc., have been removed for sake of clarity.

**SPOILER ALERT: David, understandably, does NOT give us a specific number. He gives us the answer we all expected, that of a responsible CEO. As he says, “specifics around pricing and regulatory ‘really need to be managed and played out appropriately'” (in other words, NOT eagerly telling us “FX-322 WILL COST EXACTLY THESE MANY DOLLARS” while the drug is still in phase 2a clinical trials).

Alas.

Specifics? Best I can do is this:

HOST: […] walk us through your thinking around the target patient population and maybe some kind of rough ideas around pricing and reimbursement […]

DAVID LUCCHINO: I’m still evolving our understanding of this as we really work in partner with the FDA to understand exactly the true, we think, impact of our therapy. So it’s hard for me to speak in any absolutes. We know that the market is absolutely substantial and the unmet clinical need is very, very high. We think that hearing aids will continue to have a real role and be a good option for patients, though we think having a therapy that can truly start to heal someone’s hearing and create a healthy cochlea, if you will, is going to be a very strong value proposition both with or without hearing aids. I think that specifics around pricing and regulatory, those really need to be managed and played out appropriately. I think that we’re aware of what hearing aids are priced at, and we’re aware of what cochlear implants are priced at, and how hearing aids are handled from a regulatory standpoint and our goal is to deliver a highly effective therapy and do it in a way where we can continue to build out a very successful company that investors will recognize for years and years to come.

HOST: Excellent, super helpful.

SOURCE: Where is this from? These comments were made during a live Q&A at the Oppenheimer Virtual Fall Healthcare Life Sciences & MedTech Summit, which took place on Tuesday, September 22, 2020 at 10:00 am Eastern Time.

As David’s comments suggest, a lot of work goes into determining the price of a treatment such as FX-322. Meanwhile, the drug only recently completed enrollment for its Phase 2a study.

So don’t expect any “Hey it will cost THIS many dollars” answers yet…

For now, this recent commentary is the most recent and up-to-date information regarding FX-322’s price tag. Straight from the CEO’s mouth.

And let’s be honest, it is the reply we all expected… But with some interesting “price anchoring” thrown in with the mention of hearing aid costs (average price: $2372) and cochlear implant costs (average price: between $30,000-$100,000).***

Why would David mention those price points? How do drug companies calculate price? How do comparisons and price anchoring factor into that calculation?

Hmmmm…

Let the speculation begin!

Excellent Super Helpful vague troll face meme

LINK TO VIDEO: If you want to watch the interview, here is a link to the video recording of the Frequency Therapeutics virtual event webcast (the FX-322 pricing-related comments begin at around 39:00):

https://wsw.com/webcast/oppenheimer5/freq/2713518

And…

If you want an easy way to follow FX-322 including any future updates RE: cost of FX-322, join the weekly email update list. It’s a free, once-weekly email [starting soon] that lists all the new links that were added to this site’s front page during the previous 7 days. No spam, no nonsense.

***Reference: https://www.hearingtracker.com/how-much-do-hearing-aids-cost, https://www.hearingtracker.com/cochlear-implants#a-how-much-do-cochlear-implants-cost.

Frequency Therapeutics Presents Results Demonstrating Sustained Improvement in Hearing Loss Patients Treated with FX-322

https://investors.frequencytx.com/news-releases/news-release-details/frequency-therapeutics-presents-results-demonstrating-sustained

Frequency Therapeutics Presents Results Demonstrating Sustained Improvement in Hearing Loss Patients Treated with FX-322

Evidence of Durable Hearing Improvements in Follow-Up with Patients from Phase 1/2 Study; Speech Intelligibility and Audibility Sustained for Up to 21 Months After Initial Dosing

Data Highlighted at the 2020 American Academy of Otolaryngology – Head and Neck Surgery (AAO-HNS) Annual Meeting

Role of protein in development of new hearing hair cells: Finding could lead to future treatments for hearing loss

https://www.sciencedaily.com/releases/2020/09/200911200012.htm

Role of protein in development of new hearing hair cells
Finding could lead to future treatments for hearing loss

Date:
September 11, 2020

Source:
University of Maryland School of Medicine

Summary:
Researchers have conducted a study that has determined the role that a critical protein plays in the development of hair cells. These hair cells are vital for hearing. Some of these cells amplify sounds that come into the ear, and others transform sound waves into electrical signals that travel to the brain.

Frequency Therapeutics Expects to Share FX-322 Phase 2a Study Results in Q2 2021

https://www.businesswire.com/news/home/20200812005136/en/

expects to achieve target enrollment by early in the fourth quarter of 2020. Based on this timeline, the Company expects to report study data in the second quarter of 2021.

Frequency Therapeutics Provides Business Updates and Reports Second Quarter 2020 Financial Results
Expects to Complete Enrollment of FX-322 Phase 2a Study for Sensorineural Hearing Loss by Early Q4 2020; Study Readout Anticipated in Q2 2021

Recently Announced Clinical Data Show FX-322 Delivery to the Cochlea and Preliminary Evidence of a Durable Clinical Benefit; Plans New Studies in Additional Patient Populations

Raised $42.3 Million Private Placement, Providing Company Runway into 2023

August 12, 2020 07:30 AM Eastern Daylight Time
WOBURN, Mass.–(BUSINESS WIRE)–Frequency Therapeutics, Inc. (Nasdaq: FREQ), a clinical-stage biotechnology company focused on harnessing the body’s innate biology to repair or reverse damage caused by a broad range of degenerative diseases, today announced business updates and financial results for the second quarter ended June 30, 2020.

“We are pleased with the steady progress in our Phase 2a study, despite the challenges of the pandemic, and we anticipate completing enrollment early in the fourth quarter of 2020 and sharing data from the study in the second quarter of 2021,” said Frequency Therapeutics Chief Executive Officer David L. Lucchino. “In the last quarter, we generated compelling cochlear drug delivery data for FX-322, as well as important durability data suggesting that some patients who were given a single injection of FX-322 in our original Phase 1/2 study maintained statistically significant improvements in word recognition between 12 and 21 months following administration. We believe that these clinical advances are important building blocks as we work to further our understanding of FX-322 drug activity and the patient populations we hope to treat.

PIPE-505 Clinical Trial Update: Pipeline adds 4 new study locations across the United States…

As anticipated, Pipeline Therapeutics has added additional clinical trial sites to its phase 1/2a study of PIPE-505 for hearing loss.

The official study record (NCT04462198), updated on August 6, 2020, now includes five study locations across the U.S., four of which are now recruiting participants:

  • Boca Raton, Florida, United States, 33487 – added July 17 – Recruiting
  • Winston-Salem, North Carolina, United States, 27103 – added July 27 – Recruiting
  • New Albany, Indiana, United States, 47150 – added August 1 – Recruiting
  • Louisville, Kentucky, United States, 40220 – added August 1 – Recruiting
  • Kansas City, Kansas, United States, 66160 – added August 4 – Not yet recruiting

This post will be updated to include any further changes to the study record. For email updates (which will be starting soon), join the announcement list while it is still open.

Pipeline Therapeutics Initiates Phase 1/2a Clinical Trial of PIPE-505 in Sensorineural Hearing Loss – Topline results expected in early 2021…

https://www.pipelinetherapeutics.com/news/pr_07-23-2020.php

Pipeline Therapeutics Initiates Phase 1/2a Clinical Trial of PIPE-505 in Sensorineural Hearing Loss
PIPE-505 is the first small molecule developed specifically for the treatment of sensorineural hearing loss (SNHL) associated with speech-in-noise impairment
Topline results expected in early 2021
SAN DIEGO, July 23, 2020 – Pipeline Therapeutics, a biopharmaceutical company focused on the development and commercialization of first-in-class small molecules for neuroregeneration, today announced the initiation of a Phase 1/2a trial of the company’s lead product candidate, PIPE-505, a small molecule gamma secretase inhibitor (GSI), in sensorineural hearing loss (SNHL) associated with hearing speech in noisy environments.

UPDATE: Pipeline Therapeutics Begins Recruiting Patients for Phase 1/2a Study of PIPE-505 for SNHL

This is a follow-up post to the previous PIPE-505 clinical trial update from July 8 where we explained how “patient recruitment could begin any day now.”

Today, less than two weeks later, that forecast proved accurate: the PIPE-505 trial is now RECRUITING, according to the official study record (NCT04462198), which had its Recruitment Status updated yesterday.

Here is an excerpt from that ClinicalTrials.gov record:

STUDY TITLE: A Phase I/IIa, Randomized, Double-Blind, Placebo-Controlled, Safety, Pharmacokinetic, and Preliminary Efficacy Study of Unilateral Intratympanic PIPE-505 in Subjects With Sensorineural Hearing Loss Associated With Speech-in-Noise Impairment

Recruitment Status: Recruiting
First Posted: July 8, 2020
Last Update Posted: July 20, 2020

DESCRIPTION: This is a randomized-controlled, double-blind study of PIPE-505 or placebo given as an injection one time in subjects with sensorineural hearing loss associated with speech-in-noise difficulty. Visits to the clinic will occur at baseline, dosing, and days 1, 7, 14, 30, 60 and 90 after treatment. Safety will be assessed by periodic measurement of vital signs, ear examination, electrocardiogram (ECG), blood laboratory analyses and occurrence of adverse events (AE). Efficacy will be assessed by periodic audiometry and other audiological tests.

ClinicalTrials.gov Identifier: NCT04462198

Where is the PIPE-505 study located?

As of July 21, 2020, there is only one recruitment location (Florida) for the trial. But it is common for studies like this one to expand and add more locations across the country and sometimes internationally, too. We expect more recruitment sites to be added in the next 4-6 weeks, although we do not have an exact list of those locations… yet…

UPDATE: August 29, 2020 – A second recruitment location (North Carolina) has been added to the list. (More to come?)

More updates to follow for PIPE-505 and other up-and-coming hearing loss treatments. Keep an eye on the front page of this website for updates, or get email updates (it’s an upcoming once-weekly email newsletter – no spam, no third parties, privacy respected).

People on the email list will get first access to new versions of this website that track more research from more sources…

Questions? Comments? Corrections? Collaborations? Send an email to michael@urgentresearch.com and say hello.

Pipeline Therapeutics Initiates Phase 1/2 Clinical Trial of PIPE-505 for Sensorineural Hearing Loss

The study titled, Phase I/IIa Study Evaluating Safety and Efficacy of an Intratympanic Dose of PIPE-505 in Subjects With Hearing Loss, was added to the official ClinicalTrials.gov databased on July 8, 2020.

The recruitment status of the clinical trial is currently set to “Not yet recruiting.” However, that could change very soon, considering a) the follow-up period for trial participants after the initial drug administration lasts 3 months, and b) the anticipated primary completion date of the study is four months away, in November 2020.

These details suggest that patient recruitment could begin any day now and – assuming there are no changes to the study’s current schedule – probably no later than 4-6 weeks from now.

UPDATE (current as of July 21, 2020): the PIPE-505 study is now recruiting patients… see this follow-up post for details or visit the official study page using the link below:

https://clinicaltrials.gov/ct2/show/NCT04462198

Here is further reading about PIPE-505, a small molecule gamma secretase inhibitor (GSI) that will be delivered to select trial participants as a one-time intratympanic injection:

PIPE-505 is the first small molecule developed specifically for the treatment of sensorineural hearing loss (SNHL) associated with cochlear synaptopathy. The therapeutic focus, regeneration of the cochlear synapse, should augment signal-to-noise processing and manifest as improved speech-in-noise comprehension, a chief auditory complaint and unmet need of patients with SNHL.

Source: https://www.pipelinetherapeutics.com/science/synaptogenesis.html

A simpler way to make sensory hearing cells

https://www.sciencedaily.com/releases/2020/07/200701134242.htm

A simpler way to make sensory hearing cells
Date:
July 1, 2020
Source:
Keck School of Medicine of USC
Summary:
Scientists are whispering the secrets of a simpler way to generate the sensory cells of the inner ear. Their approach uses direct reprogramming to produce sensory cells known as ‘hair cells,’ due to their hair-like protrusions that sense sound waves.

Otonomy Provides Update on OTO-413 Clinical Trial: Results from Phase 1/2 study of OTO-413 for hearing loss expected in fourth quarter of 2020

https://www.globenewswire.com/news-release/2020/06/15/2048357/0/en/Otonomy-Provides-Update-on-Clinical-Trials-and-Development-Programs.html

Otonomy Provides Update on Clinical Trials and Development Programs

June 15, 2020 16:05 ET | Source: Otonomy, Inc.

  • Results from Phase 3 trial of OTIVIDEX® in Ménière’s disease expected in first quarter of 2021
  • Results from Phase 1/2 trial of OTO-313 in tinnitus expected in July 2020
  • Results from Phase 1/2 trial of OTO-413 in hearing loss expected in fourth quarter of 2020

SAN DIEGO, June 15, 2020 (GLOBE NEWSWIRE) — Otonomy, Inc. (Nasdaq: OTIC), a biopharmaceutical company dedicated to the development of innovative therapeutics for neurotology, today provided an update on its product pipeline and the timeline to results for the company’s three ongoing clinical trials, including the Phase 3 trial of OTIVIDEX in Ménière’s disease. The company will host a conference call and webcast today at 4:30 p.m. ET to review these updates.

NO COVID-19 SLOWDOWN: Frequency Therapeutics Adds Another Recruitment Site for FX-322 Phase 2a Study

Frequency Therapeutics has once again updated the official Study Record of its Phase 2a clinical trial of FX-322 in Adults With Stable Sensorineural Hearing Loss.

The update – which includes a new clinical trial site in Austin, Texas – was posted to ClinicalTrials.gov on April 10, 2020.

No Slowdown Due to COVID-19?

It looks like the FX-322 trial is still moving forward as expected, running on schedule.

Usually, a small change to a study record would not seem like such big news.

However, in the context of COVID-19, it is noteworthy. And uplifting! Why?

Consider this: while many clinical trials across the world are experiencing massive slowdowns and stoppages due to COVID-19, the FX-322 Phase 2a trial is expanding its presence to yet another location in the United States. Expanding!

That is not to say the trial has not been affected by COVID-19. For example, patient recruitment efforts and other logistics have probably become more challenging.

However, despite all that is happening, what we see with this update is more activity and signs of life. Things are happening. Plus, we have proof that the study is not paused or stopped. In fact, there is no sign of any delay at all…

FULL SPEED AHEAD!

The estimated study completion date (September 30, 2020) remains unchanged. Repeat: the estimated completion date of the FX-322 trial has NOT been pushed back despite the impact of COVID-19, according to the latest study record.

Small update, big news.

Link to official study page:

https://clinicaltrials.gov/ct2/show/NCT04120116

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Strekin AG Completes Phase 3 Clinical Study of STR001 to Restore Hearing in Patients with SSNHL

Strekin AG, a Swiss-based biopharmaceutical company focused on developing new treatments to reverse hearing loss, has completed its Phase 3 clinical trial of the investigational drug STR001 in patients with Sudden Sensorineural Hearing Loss (SSNHL).

According to the official study record (Source: ClinicalTrials.gov), the Status of Study NCT03331627, Safety and Efficacy of STR001-IT and STR001-ER in Patients With SSHL, was changed from “Recruiting” to “Completed” on March 25, 2020. The actual completion date of the study was updated to February 6, 2020.

The purpose of this international, randomized, placebo-controlled, Phase 3 study, officially titled Phase III Multicenter, Double-blind, Placebo-controlled, Study Evaluating the Safety, and Efficacy of STR001 Treatment in Adults With Sudden Sensorineural Hearing Loss, was to evaluate the ability of STR001 to restore hearing in patients following a SSNHL event.

If the results are promising, STR001 could become the first approved treatment for SSNHL patients.

The previous update related to this clinical trial of STR001 was from over six months ago, on September 12, 2019. That is when Strekin AG announced in a press release the completion of patient recruitment for the study (which involved 165 patients).

Prior to that, the last change to the study record was almost a year ago, on April 10, 2019. That is when the study began recruiting patients, according to the official study page.

Source:

https://clinicaltrials.gov/ct2/show/NCT03331627?type=Intr

To get more exclusive (and early, early, early) hearing loss treatment-related news and updates, remember to join the mailing list for HearingLossTreatmentReport.com Email Updates. It’s free and you can unsubscribe at any time. One email per week – a simple list of links that were posted on the site during the previous 7 days. No spam or nonsense, completely private.

INVITATION TO RESEARCHERS, INDUSTRY PROFESSIONALS, and RESEARCH-SEEKING PATIENTS: For more information about how this site works, and how it automatically gathers all the latest and most relevant hearing loss treatment-related updates non-stop, 24/7… send an email to michael@urgentresearch.com and say hello.
– Michael S.

P.S. Here are three other hearing-related “treatment report” sites that might interest you:

COMPLETED: Novartis Phase 1/2 Trial of CGF166, an Inner Ear Gene Therapy for Hearing Loss

The status of study NCT02132130 (Safety, Tolerability and Efficacy for CGF166 in Patients With Unilateral or Bilateral Severe-to-profound Hearing Loss), was changed from “Active, not recruiting” to “Completed” on March 19, 2020.

According to the official study record, the actual completion date of the trial was December 9, 2019.

The previous update to this clinical trial of CGF166 was posted just over four months ago, on November 15, 2019. That is when the study status was changed from “Recruiting” to “Active, not recruiting.”

Source:
https://clinicaltrials.gov/ct2/show/NCT02132130

Discovery of a pharmacological treatment that could “wake up” the human body’s ability to naturally regenerate lost hair cells and reverse hearing loss

Many fish, frogs, and birds possess special regeneration capacities that allow them to fully recover from hearing impairments and balance dysfunctions caused by lost hair cells.

Humans and other mammals, however, do NOT have this ability.

Sadly, our mammalian ears are vulnerable to permanent hearing loss and balance deficits.

But that could soon change…

Because new research from Jeff T. Corwin at the University of Virginia appears to have uncovered the reason for the permanent nature of hair cell loss in humans. The findings identify why certain creatures can recover from hearing damage and why humans cannot.

The most exciting part?

The team behind the research, part of Corwin’s Laboratory of Inner Ear Sensory Hair Cell Regeneration, has discovered a pharmacological treatment that could “wake up” the special supporting cells that can allow lost hair cells to regenerate in humans.

To learn more about how it works, here is a link to the study itself — which was published on February 20, 2020 in the Journal of Neuroscience.

EGF and a GSK3 Inhibitor Deplete Junctional E-cadherin and Stimulate Proliferation in the Mature Mammalian Ear.

Here is the abstract:

J Neurosci. 2020 Feb 19;:
Authors: Kozlowski MM, Rudolf MA, Corwin JT

Sensory hair cell losses underlie the vast majority of permanent hearing and balance deficits in humans, but many non-mammalian vertebrates can fully recover from hearing impairments and balance dysfunctions, because supporting cells (SCs) in their ears retain lifelong regenerative capacities that depend on proliferation and differentiation as replacement hair cells. Most SCs in vertebrate ears stop dividing during embryogenesis, and soon after birth vestibular SCs in mammals transition to lasting quiescence as they develop massively thickened circumferential F-actin bands at their E-cadherin-rich adherens junctions.

Here, we report that treatment with EGF and a GSK3 inhibitor thinned the circumferential F-actin bands throughout the sensory epithelium of cultured utricles that were isolated from adult mice of either sex. That treatment also caused decreases in E-cadherin, β-catenin, and YAP in the striola, and stimulated robust proliferation of mature, normally quiescent striolar SCs. The findings suggest that E-cadherin-rich junctions, which are not present in the SCs of the fish, amphibians, and birds which readily regenerate hair cells, are responsible in part for the mammalian ear’s vulnerability to permanent balance and hearing deficits.

SIGNIFICANCE STATEMENT

Millions of people are affected by hearing and balance deficits that arise when loud sounds, ototoxic drugs, infections, and aging cause hair cell losses. Such deficits are permanent for humans and other mammals, but non-mammals can recover hearing and balance after supporting cells regenerate replacement hair cells. Mammalian supporting cells lose the capacity to proliferate around the time they develop unique, exceptionally reinforced, E-cadherin-rich intercellular junctions. Here, we report the discovery of a pharmacological treatment that thins F-actin bands, depletes E-cadherin, and stimulates proliferation in long-quiescent supporting cells within a balance epithelium from adult mice. The findings suggest that high E-cadherin in those supporting cell junctions may be responsible, in part, for the permanence of hair cell loss in mammals.

PMID: 32079647 [PubMed – as supplied by publisher]

Additional research shows that there is a U.S. Provisional Patent Application related to the research posted here is currently pending. The application number is 62/951,996 and it was filed on December 20, 2019. The patent applicant is Jeffrey T. Corwin, and the other inventors listed include Mark Rudolf and Mikolaj Kozlowski.

Hearing Loss Treatment Report will continue to keep an eye on this promising new (potential) hearing loss treatment, which involves treatment with an EGF and a GSK3 inhibitor, and is currently being tested in mice. But considering the patent filing and strong evidence, human trials will surely follow.

Want updates? Remember to sign up for free weekly email updates, here. Especially if you want to know about new hearing loss drugs and experimental treatments as soon as possible.

Questions? Comments? Corrections? Feedback?

Send an email to michael@urgentresearch.com and say hello. This site is almost completely automated (except for occasional “exclusive” articles like this one), but there is a human behind the scenes.

FX-322 Phase 2a Clinical Trial Update: 4 new recruitment sites… plus, changes to eligibility criteria…

Frequency Therapeutics updates official Study Record of Phase 2a clinical trial, FX-322 in Adults With Stable Sensorineural Hearing Loss.

The changes were posted to ClinicalTrials.gov on January 29, 2020 and involve: a) four new study locations, and b) adjustments to the eligibility criteria.

Interestingly, the opening of any additional U.S. sites could add new information to a past statement made by Frequency Therapeutics Chief Executive Officer, David Lucchino, who said, “We have opened all U.S. sites for our Phase 2a study of FX-322,” according to a November 18, 2019 press release.

More importantly, however, is the great opportunity these new locations could provide to any interested (and eligible) patients living in New York, Texas, Utah, or Virginia.

Clinical Trial Recruitment Locations: EXTENDED EDITION

The following four locations were added to the list of clinical trial sites:

United States, New York
Amherst, New York, United States, 14226

United States, Texas
San Antonio, Texas, United States, 78258

United States, Utah
Salt Lake City, Utah, United States, 84102

United States, Virginia
Richmond, Virginia, United States, 23235

As of February 4, 2020, these four new locations are not yet recruiting patients. However, that could change at any moment. Meanwhile, the other recruitment sites — which were posted back in October — are still actively recruiting.

The other recent changes to the FX-322 clinical trial record involve the study’s Eligibility Criteria. Changes were made to both the Inclusion and Exclusion criteria.

FX-322 Trial Eligibility: REMASTERED

Inclusion Criteria (Nov 2019 vs. Feb 2020)

BEFORE:
Established diagnosis of sensorineural hearing loss by standard audiometric measures that is stable for ≥ 6 months prior to the Screening Visit [no changes greater than 5 decibels (dB) in anyfrequency].

AFTER:
Established diagnosis of stable sensorineural hearing loss by standard audiometric measures for ≥ 6 months prior to the Screening visit (no changes in air conduction greater than 10 dB at a singlefrequency or greater than 5 dB at two contiguous frequencies from the prior audiogram to the Screening audiogram in the study ear).

Exclusion Criteria (Nov 2019 vs. Feb 2020)

BEFORE:
Any conductive hearing loss of 10 dB or more at two or more frequencies in either ear.

AFTER:
Any conductive hearing loss of greater than 15 dB at a single frequency or greater than 10 dB at two or more contiguous octave frequencies in the study ear at the Screening visit or on the prior audiogram (if the Investigator feels there is not a true conductive hearing loss, the Medical Monitor should be consulted).

That’s all for now.

Note: The next actually interesting FX-322 progress update should be arriving in June, which is when Frequency Therapeutics could be ready to report top-line data from the trial.

Want more exclusive hearing loss treatment-related updates? Then you should subscribe to the free email newsletter.

Looking for updates for other related conditions? Check out these other “Treatment Report” pages: Tinnitus, Meniere’s Disease, and Hyperacusis.

Questions, comments, concerns, feedback? Email michael@urgentresearch.com and say hello.

Action on Hearing Loss and Medicines Discovery Catapult team up to launch new “Hearing Medicines Discovery Syndicate”, a collaboration designed to accelerate the “much-needed development” of treatments for hearing loss and tinnitus

http://www.pharmatimes.com/news/new_fast-track_system_for_tinnitus_and_hearing_loss_1321998

New ‘fast-track’ system for tinnitus and hearing loss

Action on Hearing Loss and the Medicines Discovery Catapult have teamed up to launch a new “Hearing Medicines Discovery Syndicate”, a collaboration designed to accelerate the “much-needed development” of treatments for hearing loss and tinnitus.

The collaboration will be partnering with the National Institute for Health Research (NIHR), with academic expertise in hearing research provided University College London Hospitals BRC, Nottingham BRC and Manchester BRC, and the Cell and Gene Therapy Catapult.

Sensorion Announces €5.6m Non-Dilutive Funding to Support SENS-401 Phase 2 Study in Sudden Sensorineural Hearing Loss; French Ministry of Armed Forces to Participate in the Study

https://www.businesswire.com/news/home/20191222005022/en/

https://www.biospace.com/article/releases/sensorion-announces-5-6m-non-dilutive-funding-to-support-sens-401-phase-2-study-in-sudden-sensorineural-hearing-loss-french-ministry-of-armed-forces-to-participate-in-the-study/

Sensorion Announces €5.6m Non-Dilutive Funding to Support SENS-401 Phase 2 Study in Sudden Sensorineural Hearing Loss; French Ministry of Armed Forces to Participate in the Study

Pipeline Therapeutics Completes $30 Million Series B Financing – Proceeds to advance PIPE-505 in hearing loss

https://www.businesswire.com/news/home/20191218005137/en/Pipeline-Therapeutics-Completes-30-Million-Series-Financing

Pipeline Therapeutics’ lead candidate, PIPE-505, is entering Phase 1b/2a testing to treat mild-to-moderate sensorineural hearing loss (SNHL) associated with cochlear synaptopathy. PIPE-505 is uniquely positioned to treat this patient population as it can have an impact on both audibility and speech intelligibility, addressing two separate pathologies associated with hearing loss.

Pipeline Therapeutics Completes $30 Million Series B Financing – Proceeds to advance PIPE-505 in hearing loss

SENS-401 shows capacity to reduce central auditory neuron loss after acoustic trauma in preclinical studies

https://www.businesswire.com/news/home/20191106005839/en/Sensorion-Announces-Oral-Presentation-New-SENS-401-Preclinical/

Sensorion Announces an Oral Presentation of New SENS-401 Preclinical Data at ISIET 2019 in Hannover: An oral presentation on the capacity of SENS-401 to reduce central auditory neuron loss after acoustic trauma in preclinical studies

SENS-401 shows capacity to reduce central auditory neuron loss after acoustic trauma in preclinical studies

Sensorion Announces a Poster Presentation of New SENS-401 Preclinical Data at SFN 2019 in Chicago

https://www.businesswire.com/news/home/20191022006061/en/Sensorion-Announces-Poster-Presentation-New-SENS-401-Preclinical

Sensorion Announces a Poster Presentation of New SENS-401 Preclinical Data at SFN 2019 in Chicago

A poster presentation on the absence of impact due to acoustic trauma on the SENS-401 inner ear exposure in preclinical studies

Sensorion Announces a Poster Presentation of New SENS-401 Preclinical Data at SFN 2019 in Chicago
A poster presentation on the absence of impact due to acoustic trauma on the SENS-401 inner ear exposure in preclinical studies

UPDATE: Frequency Therapeutics Expands List of FX-322 Clinical Trial Locations…

The phase 2a study of FX-322 in Adults With Stable Sensorineural Hearing Loss is now recruiting at 12 locations in 8 different states.

Previously, the only clinical trial location listed on the study page was in North Carolina. Not anymore…

Here is the expanded list featuring 11 new locations in 7 other states:

List of FX-322 Phase 2a Clinical Trial Locations

  1. Fresno, California, United States, 93720
  2. Torrance, California, United States, 90503
  3. Colorado Springs, Colorado, United States, 80909
  4. Boca Raton, Florida, United States, 33487
  5. Sarasota, Florida, United States, 34239
  6. Tampa, Florida, United States, 33612
  7. Louisville, Kentucky, United States, 40207
  8. Omaha, Nebraska, United States, 68118
  9. Durham, North Carolina, United States, 27713
  10. Winston-Salem, North Carolina, United States, 27103
  11. Orangeburg, South Carolina, United States, 29118
  12. San Antonio, Texas, United States, 78240

This information was found on the official FX-322 phase 2a study record page, which was recently updated to include these new study locations on Thursday, October 17, 2019.

MORE locations expected?

Could even more locations be added to this phase 2a study?

It’s possible.

However, based on the study’s estimated enrollment — limited to 96 participants — it seems unnecessary.

And what about FX-322 trials outside of the United States? Nothing to report yet. (That will be the topic of a separate post.)

Recruitment Status: Recruiting

As of Saturday, October 19, 2019, all 12 of the study locations listed above are now recruiting participants.

Frequency Therapeutics Begins Recruiting for Phase 2 Study of FX-322 in Patients with Sensorineural Hearing Loss

Frequency Therapeutics is now recruiting patients for phase 2 of its clinical trial of FX-322 in patients with sensorineural hearing loss.

This phase 2a study will assess the exploratory efficacy, as well as the local and systemic safety of single and repeat intratympanic doses of FX-322 compared to placebo in approximately 96 subjects with stable mild to moderately severe sensorineural hearing loss, with a medical history consistent with either excessive noise exposure or idiopathic sudden sensorineural hearing loss.

The study was added and updated to ClinicalTrials.gov on October 9, 2019.

There IS a placebo group… and…

Estimated enrollment is 96 participants and the first recruiting location is North Carolina.

The study is titled FX-322 in Adults With Stable Sensorineural Hearing Loss and can be found on ClinicalTrials.gov at this link: https://clinicaltrials.gov/ct2/show/NCT04120116?type=Intr&cond=Hearing+Loss&lupd_s=09%2F25%2F2019&lupd_d=14&sort=nwst

Signs of Improved Hearing With Progenitor Cell Activator (FX-322)

https://www.medpagetoday.com/meetingcoverage/aaohnsf/82242

Signs of Improved Hearing With Progenitor Cell Activator
Some pure tone improvement, significant increases in word recognition

https://journals.sagepub.com/doi/full/10.1177/0194599819858141f

WSJ: Cures for Hearing Loss May Be Found in New Drugs

https://www.wsj.com/articles/cures-for-hearing-loss-may-be-found-in-new-drugs-11568599440

Cures for Hearing Loss May Be Found in New Drugs

Researchers are trying to counter the biological causes of hearing loss—rather than just treating the effects

Researchers find proteins that might restore damaged sound-detecting cells in the ear

https://www.sciencedaily.com/releases/2019/08/190805101127.htm

Researchers find proteins that might restore damaged sound-detecting cells in the ear
Date:
August 5, 2019
Source:
Johns Hopkins Medicine
Summary:
Using genetic tools in mice, researchers say they have identified a pair of proteins that precisely control when sound-detecting cells, known as hair cells, are born in the mammalian inner ear. The proteins may hold a key to future therapies to restore hearing in people with irreversible deafness.

Research Spotlight: Avenanthramide-C (AVN-C) prevents noise- and drug-induced hearing loss while protecting auditory hair cells from oxidative stress

https://www.nature.com/articles/s41420-019-0195-1

https://www.ncbi.nlm.nih.gov/pubmed/31312524?dopt=Abstract

Avenanthramide-C prevents noise- and drug-induced hearing loss while protecting auditory hair cells from oxidative stress.

Cell Death Discov. 2019;5:115

Authors: Umugire A, Lee S, Kim D, Choi M, Kim HS, Cho HH

Abstract

Noise exposure or ototoxic drugs instigate various types of damage to the cochlea, resulting in hearing loss (HL). While the incidence of HL is growing continuously, there are, so far, no adequate drugs to prevent or treat HL. Avenanthramide (AVN), a natural product extracted from oats, has been reported to possess anti-oxidant/inflammatory properties, and protect several types of cells. In this study, we investigated whether AVN-C can protect auditory hair cells, and preserve hearing from noise trauma and ototoxic drugs. Wild-type C57BL/6 mice were used to generate several HL models. Serum and perilymphatic fluid samples were analyzed using mass spectrophotometry to detect AVN-C. AVN-C crossed the blood-labyrinth barrier, and was detected in the perilymph after systemic injection. Pretreatment by AVN-C 24โ€‰h before exposure to temporary threshold shift noise contributed to the preserving hearing. Moreover, in the case of permanent threshold shift, AVN-C provided significant protection from noise. AVN-C also strongly protected against deterioration in hearing due to kanamycin and furosemide (Kโ€‰+โ€‰F). According to the results of our scanning electron microscopy analysis, many outer hair cells (OHCs) were destroyed by noise trauma, while AVN-C prevented these losses. OHC loss due to Kโ€‰+โ€‰F was even more severe, even affecting the apex. Strikingly, AVN-C treatment maintained OHCs at a level comparable to normal cochlea. AVN-C reduced the dichlorofluorescin (DCF)-positive population in gentamicin-treated HEI-OC1 in vitro. The expressions of TNF-a, BAK, IL-1b, and Bcl-2 were attenuated by AVN-C, revealing its antioxidant effects. The results of this study show that AVN-C crosses the blood-labyrinth barrier and provide a significant protection against noise- and drug-induced ototoxicity. Hence, AVN-C is a good candidate for future therapy aimed at protecting against sensorineural HL.

PMID: 31312524 [PubMed]

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