MemberHow did they manage to enroll so many participants? This means that all emergency services in these countries have been informed of the existence of this clinical trial in order to refer patients in time to it.
Auris Medical AM-111
- Thread starter erik
- Start date
I agree that it would be very beneficial then, too. I'm wondering if there would always be a timeframe -- like the injection must happen within the first 72 hours to be effective. Obviously, it might be too early to know that. They're currently doing 72 hours but maybe they would extend that with tinnitus spikes since they can decline on their own after that time period.
There would be some other hurdles to getting treatment. Not every ENT does intratympanic steroid injections. The first two that I saw did not, but the third did because he was highly specialized. Each procedure was billed as a surgical procedure, it required some amount of skill and the proper equipment.
But if this truly works, I could definitely see more ENTs wanting to be skilled in its application.
And honestly, diagnosis practices need to improve. TT members often complain that audiograms fail to detect all hearing loss changes. There is poor imaging of the inner ear, too. If testing could better identify damage, then I think it would be easier to assess problems and receive treatment.
I don't think this fact sheet has been published in TT, see the link below or the attached file:
http://www.aurismedical.com/images/auris/Fact_Sheets/AM-111-Fact-Sheet-September-2017.pdf
It is mentioned :
Phase 2 Clinical Trials (...) AM-111 Efficacy: 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 relevant improvement in hearing threshold and speech discrimination and a higher rate of complete tinnitus remission compared with placebo.
This means that tinnitus was measured as a second outcome. It is not the case in Phase 3. Why ?
http://www.aurismedical.com/images/auris/Fact_Sheets/AM-111-Fact-Sheet-September-2017.pdf
It is mentioned :
Phase 2 Clinical Trials (...) AM-111 Efficacy: 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 relevant improvement in hearing threshold and speech discrimination and a higher rate of complete tinnitus remission compared with placebo.
This means that tinnitus was measured as a second outcome. It is not the case in Phase 3. Why ?
Coleoptere
Member
I thought anything with AM was bound to fail, but this seems promising. If they do well next time around I will make a long post apologizing and taking back everything bad I said about them.
The improvement was only shown in patients who had recent hearing loss? So this might not apply to us? Either way, if true - that's pretty amazing.
But maybe it would be helpful in the future if we suffer additional hearing loss. Trying to look for some optimism.
Nice advertising story! It truly is hilarious. Their drugs are terrific and unique (though AM-101 failed to show efficacy several times, but of course it was fault of the design of the trials!!1!), no mention of Frequency and lies about Otonomy and Audion.
cornelius
Member
- Mar 18, 2016
- 72
- Tinnitus Since
- 2002
- Cause of Tinnitus
- several acoustic traumas, always physician denial
Sinking ship full of shit, as I expected.
What a perfect time to share again this fantastic article! https://labiotech.eu/hearing-loss-tinnitus-vertigo-auris-medical/
Funniest thing is "the company is considering to seek approval despite the results". So, AM-111 is a failed bullshit, but they still want to market it! It gets better and better every day.
What a perfect time to share again this fantastic article! https://labiotech.eu/hearing-loss-tinnitus-vertigo-auris-medical/
Funniest thing is "the company is considering to seek approval despite the results". So, AM-111 is a failed bullshit, but they still want to market it! It gets better and better every day.
I'm sorry to hear that. Although AM101 didn't do much for me, Auris treated me well and had hoped they would be successful in the future.
- Apr 15, 2017
- 1,419
- Tinnitus Since
- 2008
- Cause of Tinnitus
- Noise
Auris Have been going for years well before Otonomy - if any company deserves success for their commitment to ear disorders it's them.
AM-101 next set of results expected Feb 2018.
AM-101 next set of results expected Feb 2018.
Yeah, it always puzzles me when some members here are almost gleeful when a pharmaceutical company dedicated to tinnitus and hearing loss research fails to have a successful product. If you look at the AM101 thread, there were a handful of members expressing their hopes that Auris would fail. Seems a little like cutting off their nose to spite their face to me.
For people with SSNHL who went to "profound" (>90db) AM-111 showed significant better improvement than placebo - 42.7db improvement VS 26.8db. This is so much better than having no medication at all.
https://globenewswire.com/news-rele...ase-3-Trial-of-AM-111-in-Sudden-Deafness.html
I hope they will sustain and have some great contracts with AM-111. Maybe they can find a better formula in the future.
https://globenewswire.com/news-rele...ase-3-Trial-of-AM-111-in-Sudden-Deafness.html
I hope they will sustain and have some great contracts with AM-111. Maybe they can find a better formula in the future.
One must never forget that for each failed research, a potential dead end is sealed making it easier to narrow down a cure in future research. Not to mention all the valuable information they have found during this specific research that will benefit future researches. I hope they have motivation and dedication to stick to the cause in finding a cure.
Zug, Switzerland, November 28, 2017 - Auris Medical Holding AG (NASDAQ: EARS), a clinical-stage company dedicated to developing therapeutics that address important unmet medical needs in otolaryngology, today announced top-line results from the HEALOS Phase 3 clinical trial of AM-111 in severe to profound sudden deafness. Overall, the HEALOS trial did not meet the primary efficacy endpoint of a statistically significant improvement in hearing from baseline to Day 28 compared to placebo for either active treatment groups. However, a post-hoc analysis of the subpopulation with profound acute hearing loss revealed a clinically and statistically significant improvement in the AM-111 0.4 mg/mL treatment group.
"For many patients, sudden deafness is a very frightening experience and may result in chronic hearing loss as well as a significantly reduced quality of life," commented Hinrich Staecker, MD, PhD, Professor, Department of Otolaryngology Head and Neck Surgery, University of Kansas Medical Center, Kansas City. "This is a challenging condition especially in case of profound hearing loss, where the ear is almost or completely deaf and the prognosis for recovery tends to be poor. I am pleased to see that in the HEALOS trial AM-111 showed promising therapeutic benefits in this group of patients who are most in need of them."
" The read-out from the HEALOS Phase 3 trial with AM-111 in acute inner ear hearing loss is a major milestone for Auris," added Thomas Meyer, Auris Medical's founder, Chairman and Chief Executive Officer. "Although the trial did not meet our expectations for the primary efficacy endpoint in the overall study population, we are very pleased to see the clinically and statistically significant treatment effect in the profound hearing loss subpopulation. Considering the high unmet medical need, we look forward to discussing with regulatory agencies the next steps on our path to bringing AM-111 to patients. On behalf of our team at Auris Medical, I would like to extend my sincere appreciation to the patients and investigators involved in this trial."
The HEALOS trial is a randomized, double-blind, placebo-controlled study evaluating the efficacy, safety and tolerability of AM-111. The trial was conducted in several European and Asian countries and enrolled 256 patients suffering from severe to profound sudden deafness within 72 hours from onset. Patients were randomized in a 1:1:1 ratio to receive a single dose of either AM-111 0.4 mg/mL, AM-111 0.8 mg/mL or placebo, administered into the middle ear.
The hearing improvement at the three worst affected contiguous test frequencies at Day 28 was 38.4 dB for patients in the AM-111 0.4 mg/mL group compared to 33.4 dB for the placebo group (p=0.226). For patients in the AM-111 0.8 mg/mL group the improvement was 36.6 dB (p=0.448). Post-hoc analysis in the subpopulation of patients with profound hearing loss[1] (n=98) showed an improvement at Day 28 of 42.7 dB in the AM-111 0.4 mg/mL group vs. 26.8 dB in the placebo group, which was statistically significant (p=0.0176). The improvement was 37.3 dB in the AM-111 0.8 mg/mL group (p=0.126). In addition, AM-111 was well tolerated and the primary safety endpoint was met. There was no significant difference in the occurrence of clinically relevant hearing deterioration between either of the active treated groups and the placebo group at Day 28.
Based on the findings from the HEALOS trial, Auris Medical has concluded that the very similar design of the currently ongoing ASSENT trial is no longer adequate for testing AM-111. Therefore the ASSENT trial will be terminated early.
"For many patients, sudden deafness is a very frightening experience and may result in chronic hearing loss as well as a significantly reduced quality of life," commented Hinrich Staecker, MD, PhD, Professor, Department of Otolaryngology Head and Neck Surgery, University of Kansas Medical Center, Kansas City. "This is a challenging condition especially in case of profound hearing loss, where the ear is almost or completely deaf and the prognosis for recovery tends to be poor. I am pleased to see that in the HEALOS trial AM-111 showed promising therapeutic benefits in this group of patients who are most in need of them."
" The read-out from the HEALOS Phase 3 trial with AM-111 in acute inner ear hearing loss is a major milestone for Auris," added Thomas Meyer, Auris Medical's founder, Chairman and Chief Executive Officer. "Although the trial did not meet our expectations for the primary efficacy endpoint in the overall study population, we are very pleased to see the clinically and statistically significant treatment effect in the profound hearing loss subpopulation. Considering the high unmet medical need, we look forward to discussing with regulatory agencies the next steps on our path to bringing AM-111 to patients. On behalf of our team at Auris Medical, I would like to extend my sincere appreciation to the patients and investigators involved in this trial."
The HEALOS trial is a randomized, double-blind, placebo-controlled study evaluating the efficacy, safety and tolerability of AM-111. The trial was conducted in several European and Asian countries and enrolled 256 patients suffering from severe to profound sudden deafness within 72 hours from onset. Patients were randomized in a 1:1:1 ratio to receive a single dose of either AM-111 0.4 mg/mL, AM-111 0.8 mg/mL or placebo, administered into the middle ear.
The hearing improvement at the three worst affected contiguous test frequencies at Day 28 was 38.4 dB for patients in the AM-111 0.4 mg/mL group compared to 33.4 dB for the placebo group (p=0.226). For patients in the AM-111 0.8 mg/mL group the improvement was 36.6 dB (p=0.448). Post-hoc analysis in the subpopulation of patients with profound hearing loss[1] (n=98) showed an improvement at Day 28 of 42.7 dB in the AM-111 0.4 mg/mL group vs. 26.8 dB in the placebo group, which was statistically significant (p=0.0176). The improvement was 37.3 dB in the AM-111 0.8 mg/mL group (p=0.126). In addition, AM-111 was well tolerated and the primary safety endpoint was met. There was no significant difference in the occurrence of clinically relevant hearing deterioration between either of the active treated groups and the placebo group at Day 28.
Based on the findings from the HEALOS trial, Auris Medical has concluded that the very similar design of the currently ongoing ASSENT trial is no longer adequate for testing AM-111. Therefore the ASSENT trial will be terminated early.
Update on AM-111: http://phx.corporate-ir.net/Externa...9Njg2MTg4fENoaWxkSUQ9Mzk2NDMzfFR5cGU9MQ==&t=1
They are now focused on profound SSHL.
They are now focused on profound SSHL.
- Aug 14, 2013
- 2,455
- Tinnitus Since
- Resolved since 2016
- Cause of Tinnitus
- Unknown (medication, head injury)
So, as mentioned above, there has been an update on AM-111 today. I would characterize the update as unexpected but included both a press release and a conference call. The conference call was unusually long as it included an update from Dr. Hinrich Staecker also. Strictly speaking, there wasn't much new detail versus the update in November (where it was announced that the phase-III trial failed to meet its primary endpoint). And yet the following points were made:
Lastly, there is no point in saying the drug doesn't work: unless, the auditory insult is sufficiently great, the drug has no chance of working due to lack of JNK activation (this was the main news from the event, I would say).
But given the above legal hurdles of bringing the drug to market, it could still be a while before AM-111 enters circulation...
- The future focus for AM-111 in a market situation is for the treatment of profound sudden hearing loss.
- The phase-III trial failed because it included the overall patient population (i.e. those with both severe and profound hearing loss) and because of an unexpected superior recovery for the placebo group (vs. phase-II).
- IMPORTANT: Main news is that the target for which AM-111 works is not triggered in the patients who "only" suffered severe hearing loss. In order to benefit from the single intratympanic injection with AM-111, JNK activation is necessary (and this is only seen in patients with profound hearing loss). JNK activation is what leads to cell apoptosis (cell-programmed death).
- NOT IN THE PRESS RELEASE: Bringing AM-111 to market was alluded to possibly requiring additional enrollment of participants. The focus of such a future trial would likely include just patients with profound hearing loss (not the full study population). In Europe, there is also the possibility of getting a conditional approval from the EMA whereafter full approval can be sought by meeting certain data milestones down-the-road. The market potential for the reduced label indication of profound hearing loss would be about 25-30% of the original market.
Lastly, there is no point in saying the drug doesn't work: unless, the auditory insult is sufficiently great, the drug has no chance of working due to lack of JNK activation (this was the main news from the event, I would say).
But given the above legal hurdles of bringing the drug to market, it could still be a while before AM-111 enters circulation...
- Feb 5, 2017
- 787
- Tinnitus Since
- 2016
- Cause of Tinnitus
- Fluconazole
Could somebody put in a nutshell what's the difference between "sudden hearing loss" and "profound sudden hearing loss", while also the terms "profound" vs "severe". I am not familiar also with the term JNK. Sorry to ask, but i am interested to understand the subject of this thread.
Thank you in advance.
Thank you in advance.
Last edited:
- Aug 14, 2013
- 2,455
- Tinnitus Since
- Resolved since 2016
- Cause of Tinnitus
- Unknown (medication, head injury)
See the following slide from the presentation (differentiation between severe and profound is at 90 dB thresholds):
In both cases, sudden hearing loss is sudden, but in one case the loss of hearing is severe; in the other, profound.
I don't think many people are (myself included). AM-101 works by inhibiting the effects of glutamate, AM-111 works by inhibiting the effects of JNK (an enzyme that is involved in triggering cell death on purpose (when a cell gets too damaged to be of further use)).
AM-101 works at the receptor level (NMDA receptors); AM-111 works at the intra-cellular level.
Last edited:
- Feb 5, 2017
- 787
- Tinnitus Since
- 2016
- Cause of Tinnitus
- Fluconazole
Thank you ATEOS for your time. I always enjoy your informative posts. Take care.
I found this article today:
Efficacy and Safety of AM-111 in the Treatment of Acute Unilateral Sudden Deafness—A Double-blind, Randomized, Placebo-controlled Phase 3 Study
Objective: To confirm the efficacy and safety of AM-111 (brimapitide), a cell-penetrating c-Jun N-terminal Kinase (JNK) inhibitor, in patients suffering from severe to profound acute unilateral idiopathic sudden sensorineural hearing loss (ISSNHL).
Study design: Prospective, double-blind, randomized, placebo-controlled phase 3 study with follow-up visits on Days 3, 7, 28, and 91.
Setting: Fifty-one European and Asian sites (tertiary referral centers, private ENT practices).
Patients: Two hundred fifty-six patients aged 18 to 65 years presenting within 72 hours following ISSNHL onset with mean hearing loss ≥ 40 dB and mean threshold ≥ 60 dB at the 3 worst affected contiguous test frequencies.
Interventions: Single-dose intratympanic injection of AM-111 (0.4 or 0.8 mg/ml) or placebo; oral prednisolone as reserve therapy if hearing improvement < 10 dB at Day 7.
Main outcome measures: Hearing improvement to Day 28 was the primary efficacy endpoint; complete hearing recovery, frequency of reserve therapy used, complete tinnitus remission, improvement in word recognition were secondary endpoints. Safety was evaluated by the frequency of clinically relevant hearing deterioration and adverse events.
Results: While the primary efficacy endpoint was not met in the overall study population, post-hoc analysis showed a clinically relevant and nominally significant treatment effect for AM-111 0.4 mg/ml in patients with profound ISSNHL. The study drug and the administration procedure were well tolerated.
Conclusions: AM-111 provides effective otoprotection in case of profound ISSNHL. Activation of the JNK stress kinase, AM-111's pharmacologic target, seems to set in only following pronounced acute cochlear injury associated with large hearing threshold shifts.
This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
Source: https://journals.lww.com/otology-ne...fety_of_AM_111_in_the_Treatment_of.96524.aspx
Efficacy and Safety of AM-111 in the Treatment of Acute Unilateral Sudden Deafness—A Double-blind, Randomized, Placebo-controlled Phase 3 Study
Objective: To confirm the efficacy and safety of AM-111 (brimapitide), a cell-penetrating c-Jun N-terminal Kinase (JNK) inhibitor, in patients suffering from severe to profound acute unilateral idiopathic sudden sensorineural hearing loss (ISSNHL).
Study design: Prospective, double-blind, randomized, placebo-controlled phase 3 study with follow-up visits on Days 3, 7, 28, and 91.
Setting: Fifty-one European and Asian sites (tertiary referral centers, private ENT practices).
Patients: Two hundred fifty-six patients aged 18 to 65 years presenting within 72 hours following ISSNHL onset with mean hearing loss ≥ 40 dB and mean threshold ≥ 60 dB at the 3 worst affected contiguous test frequencies.
Interventions: Single-dose intratympanic injection of AM-111 (0.4 or 0.8 mg/ml) or placebo; oral prednisolone as reserve therapy if hearing improvement < 10 dB at Day 7.
Main outcome measures: Hearing improvement to Day 28 was the primary efficacy endpoint; complete hearing recovery, frequency of reserve therapy used, complete tinnitus remission, improvement in word recognition were secondary endpoints. Safety was evaluated by the frequency of clinically relevant hearing deterioration and adverse events.
Results: While the primary efficacy endpoint was not met in the overall study population, post-hoc analysis showed a clinically relevant and nominally significant treatment effect for AM-111 0.4 mg/ml in patients with profound ISSNHL. The study drug and the administration procedure were well tolerated.
Conclusions: AM-111 provides effective otoprotection in case of profound ISSNHL. Activation of the JNK stress kinase, AM-111's pharmacologic target, seems to set in only following pronounced acute cochlear injury associated with large hearing threshold shifts.
This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
Source: https://journals.lww.com/otology-ne...fety_of_AM_111_in_the_Treatment_of.96524.aspx
Among the main outcome measure: tinnitus remission.
Sadly, no result information about "tinnitus remission".
Maybe it will be released in a further article...
Sadly, no result information about "tinnitus remission".
Maybe it will be released in a further article...
You have to click on the "Article as PDF" on the right to see the full study. Doesn't appear to be any more effective than placebo. You can see the rest of the results in the "efficacy outcomes" section. Looks like there were some improvements over placebo in other measures related to hearing recovery.
"Complete remission of tinnitus at Day 91 was observed in 17.2%, 25.0%, and 19.2% of patients in the AM-111 0.4 mg/ml, 0.8 mg/ml, and placebo groups, respectively; the differences between groups were not significant. The improvement in WRS (word recognition score) reached 38.4, 31.0, and 29.2 percentage points at Day 28 and by Day 91 increased further to 49.2, 39.7, and 30.4 percentage points, respectively. The treatment effect for the AM-111 0.4 mg/ml group reached 18.8 percentage points ( p ¼ 0.062), and for the AM-111 0.8 mg/ml it was 9.4 percentage points ( p ¼ 0.362)."
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