Auris Medical AM-111

Auris Medical Reporting Positive Results from Phase IIb Trial with AM-111

14 Nov 2012

BASEL, Switzerland I November 13, 2012

Auris Medical announced today positive results from a phase IIb clinical trial with AM-111, its investigational drug for the intratympanic (i.t.) treatment of acute sensorineural hearing loss (ASNHL). The study demonstrated that the treatment was well tolerated and showed a statistically significant and clinically relevant treatment effect.

The double-blind, randomized, placebo-controlled phase IIb study with AM-111 was conducted in Germany, Poland and the Czech Republic, involving more than 30 sites. A total of 210 patients suffering from acute acoustic trauma or sudden deafness were enrolled within the first 48 hours following the incident. Their hearing loss, measured against a reference value, had to be at least 30 dB at the average of 3 contiguous audiometric test frequencies. Study participants received one single dose of either AM-111 at 0.4 or 2 mg/ml or placebo by way of i.t. injection and were followed for 90 days. In case of insufficient hearing re- covery by Day 7, they were given the option of receiving oral prednisolone as a reserve therapy. Preliminary results from the phase IIb study show that the local treatment with AM-111 was well tolerated. In addition, the study demonstrated a substantial improvement in hearing threshold and speech discrimina- tion score. In subjects with severe to profound hearing loss who were treated with AM-111 0.4 mg/mL, the primary study endpoint, absolute hearing improvement in the 3 most affected contiguous test frequencies from baseline to Day 7, was met (p < 0.02, compared with placebo). The outcome was confirmed by the co- primary endpoint “% of hearing loss recovered at Day 7” (p < 0.03); the odds ratio for complete hearing recovery was > 2.2. Importantly, the improvement in the speech discrimination score from baseline to Day 7 showed also a statistically significant difference between AM-111 and placebo treated study subjects (p < 0.02). The differences in hearing and speech discrimination recovery between treatment groups appeared as early as on Day 3 and were clinically relevant. Further information on the clinical trial and detailed out- comes shall be presented in a scientific journal.

“The cell penetrating peptide AM-111 represents a novel approach to treating ASNHL“, stated Professor Markus Suckfüll, Munich (Germany), coordinating investigator of the study. “The clear and clinically mean- ingful improvements observed with AM-111 in the treatment of severe to profound hearing loss demon- strate that effective otoprotection is feasible, and they appear very promising. The inclusion of a placebo arm to control for the effects of spontaneous recovery lends particular credibility to the results and will provide also a wealth of important new information for future hearing research.” Thomas Meyer, Auris Medical’s founder and Managing Director, commented: “We are very pleased with the positive results from the phase IIb trial with AM-111, which were achieved under challenging clinical conditions. The outcomes are in line with the positive results from preclinical studies conducted in various ASHNL conditions, which had demonstrated the strong otoprotective effects of the peptide.” In a next step, Auris Medical is planning to discuss the phase IIb results and further clinical development with AM-111 with regulatory agencies.

About acute sensorineural hearing loss
Acute sensorineural hearing loss may be the consequence of various insults to the cochlea. It may result e.g. from overexposure to noise, bacterial or viral infections, inflammation, vascular compromise, or a variety of other factors. In ASNHL, sensorineural structures of the inner ear – inner and outer hair cells, neurons – are damaged, as well as other structures such as supporting cells or vascular tissues. The common observation is a temporary increase in hearing thresholds, i.e. hearing loss. Thanks to cellular defences and intrinsic re- pair mechanisms, a certain amount of such hearing loss is frequently recovered in the subsequent days and weeks. The remaining hearing loss however is irreversible. ASNHL may be accompanied by other disorders of the inner ear such as dizziness or tinnitus.

When ASNHL develops into permanent hearing loss, it may have chronically debilitating consequences. Hearing loss may have serious impacts on professional and personal lives, e.g. through avoidance or with- drawal from social situations, reduced alertness and increased risk to personal safety, impaired memory and ability to learn new tasks, or reduced job performance and earning power. To date, there exists no treatment for ASNHL with proven efficacy.

About AM-111
AM-111 is a cell-permeable peptide that selectively blocks JNK MAPK mediated apoptosis of stress injured hair cells and neurons in the cochlea. Major cochlear stress incidents that may result in irreversible hearing loss include exposure to excessive noise, disturbances of the blood supply, viral or bacterial infections, and exposure to certain ototoxic substances. When administered within a therapeutic time window after the incident, AM-111 can effectively protect cochlear hair cells and neurons that would otherwise undergo apoptosis and be lost forever. AM-111’s otoprotective properties have been extensively tested and con- firmed in various animal models so far, including acute acoustic trauma, acute labyrinthitis, surgery trauma, aminoglycoside ototoxicity, semicircular canal injury in otitis media and cochlear ischemia. AM-111 has been granted orphan drug status in both the European Union and the USA for the treatment of acute sen- sorineural hearing loss. The active substance of AM-111 has been in-licensed by Auris Medical from Swiss biotechnology company Xigen S.A.

About Auris Medical
Auris Medical is a Swiss biotechnology company developing specific pharmaceutical compounds for the prevention or treatment of inner ear disorders, an area of great unmet medical need. Around the world, many million people are permanently suffering from severe hearing loss and tinnitus. Truly effective and safe treatments for these disorders are still lacking. Auris Medical is currently focusing on the development of treatments for acute inner ear tinnitus (AM-101) and for acute sensorineural hearing loss (AM-111).

 

Its good news Erik. Too late for us though

I emailed Auris some time ago. They will be planning their Phase III trials next year.

 

I really have hopes in this company. They know what they are doing. I joined their AM-101 study and it seems to have helped me.

Do not worry too much about this time frame. I was told it is only a theory and 3 months limit is arbitrary. Who knows, maybe those investigated drugs will help other sufferers too when they finally hit the market?

 

That's good to know Fish. Lets cross our fingers.

 

I apologize if this is old news and has been posted already. I've searched for it and didn't find it. Hope this isn't the same thing as AM-101.

Taken from: http://www.healthyhearing.com/report/52552-New-medicine-shows-promise-in-hearing-loss-treatment

New medicine shows promise in hearing loss treatment

Contributed by Lisa Packer, staff writer, Healthy Hearing | Thursday, October 15th, 2015

If you are one of the 22 million people in the U.S. at risk of noise-induced hearing loss, what if we told you that in the not too distant future it might be possible to cure or prevent certain types of hearing loss with a pill?

That isn’t as far-fetched as it sounds. Drug trials are underway that might make it possible to prevent or even cure some forms of hearing loss with medication by the year 2020. Currently, five drugs to treat or prevent hearing loss are in the final stages of clinical testing, with another 13 drugs in the early stages of development.

Preventing hearing loss

New research into medications shows promising results in search for hearing loss treatment and prevention.

Rather than focusing on the difficult task of regenerating structures within the ear that would restore lost hearing, many of the new drugs being tested are geared toward preventing hearing loss in the first place. That being said, there are a variety of drugs in development to cure a multitude of hearing related issues, from tinnitus to noise-induced hearing loss to damage from ototoxic medications.

One study that has shown tremendous promise is a collaboration between the Southern Illinois School of Medicine and the Department of Defense to research an amino acid called D-methionine. Testing is currently underway to determine whether the common micronutrient could help preserve hearing for those in noisy occupations, such as the military. Using soldiers at the firing range at the Army’s Drill Sergeant Instructor Course at Fort Jackson, South Carolina as subjects, Dr. Kathleen Campbell and her research partners are hoping to develop a drug that could prevent or reduce both noise-induced hearing loss and tinnitus.

The soldiers were chosen for the study due to the fact that, for them, hearing loss and tinnitus are ever present realities due to artillery and gunfire. More than 800,000 veterans are currently receiving compensation due to hearing related issues.

D-methionine is an antioxidant found in certain fermented dairy foods such as yogurt and cheese, so researchers already know it is safe for human consumption. The pre-clinical studies show that D-methionine has the potential to reverse noise-induced hearing loss if started within seven hours after the damage occurs.

Treating noise-induced hearing loss
Sound Pharmaceuticals is also looking into a drug that could help reduce oxidative damage to the ear and prevent noise-induced hearing loss. The scientists at Sound are testing a man-made compound called ebselen. So how does it work? Ebselen acts exactly like another enzyme in the body responsible for recharging a cellular antioxidant called glutathione. When glutathione is charged, it blocks the generation of reactive oxygen species, also known as ROS. Since ROS is suspected to be the oxidation process that destroys the delicate hair cells in the inner ear, blocking it would be a major victory against noise induced hearing loss.

The results, thus far, are promising. In one trial, ebselen was shown to reduce temporary hearing loss in 60 percent of those who took the drug, as opposed to only 20 percent of those who took a placebo. And ebselen works quickly; on average, those for whom hearing was restored had full hearing in just 1.3 hours. On the other hand, the wait for hearing to return was 24 hours for those given a placebo.

Possible applications for ebselen not only include reducing the risk of noise-induced hearing loss, but also for preventing hearing loss in patients exposed to certain chemotherapy drugs or the class of antibiotics known as aminoglycosides.

Repairing the damage
When it comes to repairing damage after the fact, Auris Medical might have a solution in the not too distant future. Though not currently a pill, their experimental drug AM-111 has had positive results in treating hearing loss when injected into the middle ear in gel form. The key to successful treatment with AM-111 appears to be application within 48 hours after damage occurs. AM-111 has two parts: a synthetic peptide which piggybacks onto a cross membrane transporter. When hair cells and neurons in the inner ear become stressed, whether due to loud noise, ototoxic medication or infection, they can become inflamed or die. The synthetic peptide portion of AM-111 is actually able to inhibit the enzyme that causes all of that stress (and thus damage).

“We are not targeting chronic hearing loss, but we are coming in here with the potentially first-in-class treatment for acute hearing loss,” Thomas Meyer, CEO of Auris says. “If left untreated, that acute hearing loss will become chronic.”

The drugs have potential occupational uses, such as for military personnel or firefighters, for example, as well as possible recreational uses. Perhaps in the future those attending a sporting event or concert will be able to take preventative medication ahead of time.

It is important to note that when it comes to prevention of noise induced hearing loss, researchers stress that these drugs are meant to be used as a supplement to hearing protection, not a substitute.Dr. Kathleen Campbell of SIU agrees. "This is an adjunct. This is not in place of wearing physical hearing protection. Now, one of the big advantages of pharmaceutical hearing protection is it does not cut down on situational awareness. It gives you another level of protection without sacrificing your ability to hear your surroundings."

 

This is amazing! 4 years from today is not so much

 

I have read some articles in a web site and it said the drugs for both hearing loss and tinnitus will be out in the market by 2020. I think they are serious guys

 

AM-111 is great, but it's not a cure for chronic hearing loss, it's something you take right after a noise trauma.

 

so nothing for chronic people?

I think so too. they might find a cure or curelike treatment, but only for acute people. by 2020 our T will be chronic.

 

Yeah, that means they are working for the people who have not T yet. It is not fair.

 

My T has been chronic since 2004

There are projects which target chronic hearing loss, but it won't be available in 2020.

 

Which projects are they? Stem cell therapy? I have read an article they said 5 different drugs for hearing loss and tinnitus will be out by 2020. But I do not know which studies they meant.

 

You'll find a lot of news in the "inner ear regeneration" topic.

 

Yes! hahaa but at least its something! D:

 

So we have
AM-101
AM-102
AM-111
and none is for chronic tinnitus? Or am I making it up now?

 

Just Wondering if this will also help in chronic cases, just like am-101 works on SOME chronic tinnitus?

 

Efficacy
In a Phase 2 trial, patients with ASNHL following acute acoustic trauma or sudden deafness were enrolled within 48 hours from onset. Patients with severe to profound hearing loss (i.e. hearing thresholds ≥ 60 dB at the three worst affected test frequencies) who were treated with AM-111 0.4 mg/mL showed a clinically revelant improvement in hearing threshold, speech discrimination and a higher rate of complete tinnitus remission compared with placebo.

Just wow!

 

AM-102 might be, we don't know that yet.

 

I wonder why they are still keeping it as a secret. Hmm. Something is going on behind the doors. And I hope it will turn out good for our wills. One can only hope

 

BUMP

 

They haven't started the large scale human tests yet - no secret just time and money required

 

if this had such a success rate back in 2012, why isn't it available for the new cases of tinnitus?
i don't get it, this was 4 years ago.

 

http://hearinghealthmatters.org/hea...treat-sudden-sensorineural-hearing-loss-0705/

 

Why does it not mention Tinnitus?

 

It's not the target of the drug. If it works, AM-111 will treat sudden sensorineural hearing loss, and could potentially prevent the onset of T immediately following noise exposure.

 

You guys have to understand that this might also be useful for people who are chronic. Because we are often dealing with spikes coming from new acoustic trauma after the fact, and new damage from ototoxic medicines. I believe that this will allow us to mitigate any new damage that occurs. So you can also see it as a sort of medicine that could help our tinnitus from getting any worse. That is my theory anyway. What do ya'all think?

 

Not quite practical to go through intratympanic injection whenever you feel like you have a major spike

 

There would probably need to be a measurable audiogram change in order for insurance coverage.

I did intratympanic steroid injections and they really weren't a big deal, very easy and I didn't really have pain. But they were expensive so I was thankful for insurance.

Of course, I'm not sure if this injection process would be different.

 

You are probably right, but if someone has so severe damage after attending a concert that their tinnitus went from a 2 to a 9, I am sure that is something that some people would like to have as an option. Even though it is a million miles from ideal, but nothing about this is ideal. So don't knock this option for some people.

 

I personally would have considered it, after I got my major spike where the tinnitus went from very mild to worse.