AudioCure AC102 to Treat Hearing loss and Tinnitus

[InNeedOfHelp]

AudioCure Pharma develops novel pharmaceutical therapies for the prevention and treatment of a range of hearing impairments with high, unmet medical need. Our lead candidate is a novel molecule named AC102.​

Phase 2 clinical trial has been ongoing for ~1 year.

A Study to Evaluate the Efficacy, Safety and Tolerability of a Single Injection of AC102 into the Middle Ear Compared to Oral Steroid Treatment in Patients with Sudden Hearing Loss

The drug has EMA orphan drug designation and can move faster through the approval process because of that. The clinical trial pipeline is very much packed at the moment

The primary focus of AudioCure's development program for AC102 is acute hearing loss and acute tinnitus. Currently there are no approved drug treatments available for these disorders. Our front-runner molecule has undergone comprehensive preclinical research which demonstrates that it acts upon the sensory cells and neurons with their connections that are central to the hearing process. As no other drug has shown any such action, AC102 has the potential to become the first breakthrough causative therapy (i.e. treatment aimed at eliminating the cause) for acute hearing loss and acute tinnitus. By treating these conditions as soon as possible after onset, it is our vision to prevent the development of long-term, chronic hearing impairments.

Outer hair cells act as amplifiers in the hearing process. Damage by an acoustic trauma can lead to their programmed cell death, a process known as apoptosis. Once dead, these cells cannot be replaced and their amplification role is lost. Our studies demonstrate that AC102 significantly reduces apoptosis of outer hair cells following acute hearing loss.

AC102 enhances protection and repair processes

Following acute hearing loss, the inner hair cells can also lose their synaptic connection to the auditory nerve. In the presence of AC102 these connections may be restored in an acoustic trauma preclinical model. This suggests that AC102 enhances factors that are central to important protection and repair processes, giving the cells and synaptic connections of the auditory system a greater chance of survival after injury.

In summary, AC102 acts as an antagonist of the multitude of pathological processes leading to hearing loss.​

 

[HopeForSilence]

AudioCure's focus is on "acute hearing loss and acute tinnitus".

 

[Jupiterman]

Would be great if it had potential beyond the acute phase where likely 99.9% of tinnitus sufferers are.

 

[DimLeb]

The fact that they are targetting acute tinnitus and hearing loss is simply stupid---or they want to bring a scam product. As everyone knows, the ear can sometimes repair itself from a recent insult, so how are they supposed to distinguish what the drug really did in the acute period?

I call BS on this one.

 

[NikoD]

Recruitment of Sudden Hearing Loss Patients for Clinical Trial: Novel Compound AC102 Outperforms Corticosteroids Preclinically

While corticosteroids are widely used to treat Sudden Sensorineural Hearing Loss (SSNHL), there is still no therapy with proven efficacy and regulatory approval for this debilitating condition. To address this high unmet medical need, AudioCure Pharma is developing the investigative medicine AC102, which is applied via single intratympanic injection (A) and outperformed corticosteroids in hearing loss models. In these models, AC102 almost completely restored noise-induced hearing loss across all frequencies tested by preventing apoptosis of sensory hair cells (B) and synaptic disconnection of inner hair cells to the auditory nerve (C).

AudioCure Pharma Awarded for Therapeutic Small Molecule for Hearing Loss

AudioCure Pharma GmbH has been awarded for its innovative compound AC102 by the Hearing Technology Innovator Awards, honoring technological innovation and breakthroughs in the hearing industry.

AudioCure is developing the therapeutic small molecule AC102 to treat hearing impairments including Sudden Sensorineural Hearing Loss (SSNHL). While corticosteroids are the standard treatment, health authorities have never approved them as there is no clear evidence of a clinically relevant benefit to the patient. AudioCure is conducting extensive research to develop targeted and effective therapies to address this high unmet medical need.

"The Innovator Awards aim to acknowledge the individuals and organizations that transform groundbreaking hearing care concepts into reality," says Robert Traynor, EdD, MBA, FNAP, member of the 2023 Awards program judge's panel. "Companies like AudioCure are playing a pivotal role in advancing innovation throughout the industry."

In preclinical hearing loss models, a single application of AC102 in the middle ear almost completely restores hearing, strongly outperforming multiple doses of corticosteroid therapy. After AC102 was demonstrated as safe and well-tolerated in healthy volunteers, a Europe-wide Phase 2 clinical trial is currently underway evaluating the efficacy of AC102 compared to corticosteroids. Patients with severe to profound SSNHL can be enrolled within five days of symptom onset at up to 50 study centers, including in Austria, Germany, The Czech Republic, The Netherlands, Poland, and Serbia.

"Receiving the Hearing Technology Innovator Award underscores the urgent need for advanced solutions in treating conditions like SSNHL," says Reimar Schlingensiepen, CEO of AudioCure. "It also honors the groundbreaking innovation by our founder, Prof. Hans Rommelspacher. Our ongoing Phase 2 clinical trial represents a significant step towards a transformative solution. This recognition fuels our commitment to redefine the standards-of-care in hearing therapeutics."

Personally for me it has to be this part:

While corticosteroids are widely used to treat Sudden Sensorineural Hearing Loss (SSNHL), there is still no therapy with proven efficacy and regulatory approval for this debilitating condition. To address this high unmet medical need, AudioCure Pharma is developing the investigative medicine AC102, which is applied via single intratympanic injection (A) and outperformed corticosteroids in hearing loss models. In these models, AC102 almost completely restored noise-induced hearing loss across all frequencies tested by preventing apoptosis of sensory hair cells (B) and synaptic disconnection of inner hair cells to the auditory nerve (C)

More and more research suggests hair cells aren't the first thing to go when the cochlea experiences trauma but synapse loss between hair cells and spiral ganglion neurons.

Good luck with the trials, it seems they are recruiting in Europe! Excellent news to start off 2024.

 

[Nick47]

More and more research suggests hair cells aren't the first thing to go when the cochlea experiences trauma but synapse loss between hair cells and spiral ganglion neurons.

I agree. Rinri Therapeutics are taking the auditory nerve approach as are Hough Ear Institute. There are recent findings on auditory nerve damage leading to tinnitus.

 

[Note]

Would AC102 also be helpful for acute acoustic trauma?

 

[NikoD]

Would AC102 also be helpful for acute acoustic trauma?

The trials are limited to those with SSNHL that occurred less than 120 hours ago. I still don't know how this compound works. Phase 2 is trying to determine if it works better than corticosteroids in humans. We do see more evidence that those with tinnitus may have had some type of dysfunction / trauma to the cochlea even without known acoustic events, any drugs that are shown to be protective of the cochlea might be of benefit to our community.

Their models suggest it has outperformed corticosteroids but let's wait to see what the trials say. Corticosteroids' action in the cochlea is complex and I'd suggest reading papers on theories why we use them in the first place. One theory (as literature suggests) is Dexamethasone reduces macrophage polarization from M1 and is a potent M2 polarizer. This means less inflammation (immune system destroying cells) and more macrophages that try to heal (m2). This field is really complicated as it's not as simple as what I paraphrased.

This evening I will try and see if there's any more literature on the compound AC102 being trialed as I'd like to know more.

 

[Street Novelist]

I so badly want to believe in this, but every time I get my hopes up, it always fails.

What they say in the press release sure does sound promising.

Here's to hoping this one works!

 

[NikoD]

I so badly want to believe in this, but every time I get my hopes up, it always fails.

Me too. Phase 2 will prove if their models translate to humans. However, after reading some the literature I'm skeptical as AC102 seems to just be Prednisolone delivered through intratympanic injection (source).

And other clinical trials using Dexamethasone (a stronger drug) such as NCT00097448 or NCT00335920 showed only some improvement in hearing thresholds.

So this becomes a matter of delivery and perhaps the gel formation they've got is longer lasting than in the previous clinical trials which we know is a big problem with intratympanic injections where the drug just drains away (in some studies it's gone in less than 25 minutes.)

Interestingly SPT-2101, Spiral Therapeutics' drug, which contains Dexamethasone, uses a longer lasting gel and both this and SPT-2101 are in clinical trials at the moment.

 

[StoneInFocus]

Me too. Phase 2 will prove if their models translate to humans. However, after reading some the literature I'm skeptical as AC102 seems to just be Prednisolone delivered through intratympanic injection (source).

No, I think you are reading it wrong.

In that study the efficacy of AC102 gel is compared to that of Prednisolone.

According to this paper, "whilst the composition of AC102 and its precise mechanism of action has not been disclosed, patents filed by the company indicate that it is likely to be a 9-methyl-ß-carboline which has been found to have stimulative, protective, regenerative and anti-inflammatory effects on dopaminergic neurons."

According to one of the ARO 2024 abstracts, AC102 is a pyridoindole.

 

[NikoD]

No, I think you are reading it wrong.

In that study the efficacy of AC102 gel is compared to that of Prednisolone.

According to this paper, "whilst the composition of AC102 and its precise mechanism of action has not been disclosed, patents filed by the company indicate that it is likely to be a 9-methyl-ß-carboline which has been found to have stimulative, protective, regenerative and anti-inflammatory effects on dopaminergic neurons."

According to one of the ARO 2024 abstracts, AC102 is a pyridoindole.

Cheers. Looks like I completely misread the ClinicalTrials page. I will do better next time.