Otonomy OTO-313 — Treatment of Tinnitus

M

Michael Larsen

Member
Author
Aug 1, 2016
92
Tinnitus Since
2000
Cause of Tinnitus
Noice
#1
http://investors.otonomy.com/phoenix.zhtml?c=234082&p=irol-newsArticle_Print&ID=2325672

Developing OTO-313, an improved formulation of gacyclidine for the treatment of tinnitus.

Gacyclidine is a potent and selective N-Methyl-D-Aspartate (NMDA) receptor antagonist, a molecular class with potential for treating tinnitus based on both nonclinical and clinical studies.

A Phase 1 clinical safety trial has been successfully completed using OTO-311, a poloxamer-based formulation of gacyclidine, with no safety concerns observed.

Otonomy has shifted development to OTO-313, an alternative formulation of gacyclidine that has improved properties compared to OTO-311.

The company expects to initiate a Phase 1/2 clinical trial for OTO-313 in tinnitus patients in the first half of 2019.
 
#3
If you have been reading much about the theories mechanisms of tinnitus and the alleged mechanisms of NMDA, you'll assume that this new drug is to treat tinnitus before it's 'established' in the brain (acute tinnitus).

In my own view, a drug to treat long term chronic tinnitus, and drug in the ear is highly unlikely to do anything (unless its regeneration drugs perhaps).

The whole purpose of this drug is to stop tinnitus becoming permanent, I just wish Otonomy would confirm that, perhaps it's a sale pitch to investors, a step in the right direction for future generations but I'm more excited about XEN-1101 that gives me more hope for chronic tinnitus.
 
#7
OTO-313: Phase 1/2 trial in tinnitus patients expected to start in the second quarter of 2019 with results in the first half of 2020. OTO-313 is an improved sustained-exposure formulation of the NMDA receptor antagonist gacyclidine. A Phase 1 study of the initial formulation, OTO-311, indicated no safety concerns. The Phase 1/2 clinical trial includes an initial safety cohort followed by an exploratory efficacy study that will enroll approximately 50 patients with unilateral tinnitus. A number of exploratory efficacy endpoints will be assessed following a single intratympanic injection of OTO-313 or placebo including the Tinnitus Functional Index (TFI), a clinically validated tinnitus measure.

http://investors.otonomy.com/news-r...vides-corporate-and-product-pipeline-update-2

http://www.otonomy.com/pipeline/product-candidates/
 
#8
It's been a while since I've brushed up on these drugs, but from what I remember, this drug is similar to AM-101, except that it is supposed to be much more potent. Back in 2013, I was discouraged that AM-101 was for acute patients and emailed Auris asking if the drug would be of any benefit to chronic patients. To my delight, Thomas Meyer responded with this message:
The 3 month cut-off point for acute vs. chronic tinnitus is somewhat arbitrary – but a line somewhere has to be drawn, and this one is based on treatment guidelines. The whole point is about testing AM-101 under conditions where we can be sure that they correspond with the conditions under which we initially tested it in animal studies, i.e. a tinnitus that is still peripheral, and where the target is well inside the cochlea. As we all know, there are cases of centralized chronic tinnitus, where the target most likely shifted to the brain – we want to avoid that patients get treated who could actually not benefit from the treatment. However, since we did not see any reduction in efficacy towards the end of the 3 month window so far, we are planning to test AM-101 in a forthcoming study in a window extending to 12 months. Once the treatment gets approved (hopefully!), it will most likely be labeled / licensed for use during the acute stage.
Click to expand...

As we all know, AM-101 failed it's drug trial. However, whatever effects they initially saw didn't seem to diminish within the 3-month window, and it could be that these types of drugs work for chronic suffers too (if they're potent enough).
 
#9
patorjk said:
It's been a while since I've brushed up on these drugs, but from what I remember, this drug is similar to AM-101, except that it is supposed to be much more potent. Back in 2013, I was discouraged that AM-101 was for acute patients and emailed Auris asking if the drug would be of any benefit to chronic patients. To my delight, Thomas Meyer responded with this message:


As we all know, AM-101 failed it's drug trial. However, whatever effects they initially saw didn't seem to diminish within the 3-month window, and it could be that these types of drugs work for chronic suffers too (if they're potent enough).
Click to expand...
Is it undergoing trials or what's going on??
 
#10
I disagree with this whole model of "acute peripheral tinnitus" and want evidence of it as I subscribe to a model that tinnitus is always central, never peripheral.

The only peripheral sensation is normal hearing just like the only peripheral sensation of having a limb is actually feeling a real limb that exist, amputating a limb or damaging an important nerve in it leading to a phantom sensation the limb is generated in the brain not the lost limb.Losing a limb and losing hearing causes a lot less nerve activity not more. The central gain mechanisms is heightened with peripheral activity is lowered.

People with phantom limb syndrome report feeling a weird small stump not actually the natural feeling of their limb, just like people with tinnitus don't report hearing voices or music just simple basic tonal noises. As far as I am concerned Auris Medical was wrong, OTO-313 is a copy of a mistake and tinnitus is always central and never peripheral.

Blocking NMDA prevents hair cell and ribbon synapse death and preventing hearing loss can prevent tinnitus, that's why it only works in an acute phase.

OTO-313 is an acute hearing loss agent, OTO-413 is a valid treatment for SNHL and tinnitus in the longterm.
 
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#19
Philip83 said:
Sweet, so a Phase 1/2 trial "in hearing loss patients" in 2019. I thought it was further off. Let's put some fire to Frequency Therapeutic's feet!
Click to expand...
lets hope they all work together to the benefit of all us that are suffering.

oh wait, the god of corporate profits sad "no"

as you were soldier
 
#20
JohnAdams said:
lets hope they all work together to the benefit of all us that are suffering.
Click to expand...
You mean in a reasonable way put their collective resources together and unselfishly work towards a common goal to advance the human race with no profit incentive and without bleeding money into big payouts to a small wealthy group of stakeholders and bloated management bonuses? What are you, some kind of commie?
 
#21
Philip83 said:
You mean in a reasonable way put their collective resources together and unselfishly work towards a common goal to advance the human race with no profit incentive and without bleeding money into big payouts to a small wealthy group of stakeholders and bloated management bonuses? What are you, some kind of commie?
Click to expand...
No, I'm American.
 
#22
Philip83 said:
That's OTO-313, not OTO-413 which is against hearing loss.
Click to expand...
The whole NMDA centric model of tinnitus temporarily being peripheral isn't holding up. I don't believe acute peripheral tinnitus exist.

The Central Gain model is that tinnitus is phantom sensation of lost hearing input, and at least one of the several forms of hyperacusis could be phantom pain for missing auditory nerve fibers.

https://www.tinnitustalk.com/threads/update-on-am-101-aka-keyzilen.15942/page-4#post-350886

https://www.tinnitustalk.com/thread...its-cracked-up-to-be.29400/page-2#post-360783

NMDA floods the cochlea after acoustic trauma, and causes more hearing loss, more hearing loss = worse tinnitus. Blocking NMDA blocks hearing loss and prevents tinnitus.

This drug could work but the science behind it is wrong.

I'd love to be proven wrong.
 
#23
Contrast said:
The whole NMDA centric model of tinnitus temporarily being peripheral isn't holding up. I don't believe acute peripheral tinnitus exist.

The Central Gain model is that tinnitus is phantom sensation of lost hearing input, and at least one of the several forms of hyperacusis could be phantom pain for missing auditory nerve fibers.

https://www.tinnitustalk.com/threads/update-on-am-101-aka-keyzilen.15942/page-4#post-350886

https://www.tinnitustalk.com/thread...its-cracked-up-to-be.29400/page-2#post-360783

NMDA floods the cochlea after acoustic trauma, and causes more hearing loss, more hearing loss = worse tinnitus. Blocking NMDA blocks hearing loss and prevents tinnitus.

This drug could work but the science behind it is wrong.

I'd love to be proven wrong.
Click to expand...
I'm also confused why they are digging themselves further into the rabbit hole of AM-101 when the results have been so poor up until now... I mean, why?
 
#25
Johan_L said:
I had temporary silence with Fentanyl after 3 years of T, i.e. non acute. Are they not going for the same mechanism? (which obviuosly works?)
Click to expand...
What mechanism 0__0 nice btw on the silence!
 
#26
this thread bound to have the same kind of shitposting that am-101 thread did.
but we don't know about "MUH ACUTE WINDOW!"


It should atleast be renamed to Otonomy Oto-313 early stage treatment for Tinnitus.

but not it has to be called "treatment of tinnitus" now normies that lurk the site think this will be the cure for all of us regardless if they had tinnitus for 20 years or 20 minutes.



 
#27
Philip83 said:
I'm also confused why they are digging themselves further into the rabbit hole of AM-101 when the results have been so poor up until now... I mean, why?
Click to expand...

It looks like small scale trials have shown promise:

https://www.researchgate.net/public...perfusion_on_tinnitus_in_humans_A_case_series

It also appears as if their test subjects were not people who have recently developed tinnitus, but people who've had it for a while - but I don't have access to the full paper so I'm not sure. I imagine Otonomy has done some of their own internal trials too, otherwise it wouldn't make much sense to pour money into this.
 
#28
patorjk said:
It looks like small scale trials have shown promise:

https://www.researchgate.net/public...perfusion_on_tinnitus_in_humans_A_case_series

It also appears as if their test subjects were not people who have recently developed tinnitus, but people who've had it for a while - but I don't have access to the full paper so I'm not sure. I imagine Otonomy has done some of their own internal trials too, otherwise it wouldn't make much sense to pour money into this.
Click to expand...

Here is the full paper
 

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#29
Those case studies are really interesting. I can't figure out how to edit my post, but according to the paper the subjects they chose had had tinnitus for less than a year. Now I'm curious if Otonomy has done any testing to see if the drug is effective on people who've had tinnitus more than a year, since their website doesn't list anything about OTO-313 being for acute tinnitus.
 

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