Otonomy OTO-313 — Treatment of Tinnitus

[Philip83]

Following the positive Phase 1/2 trial, Otonomyconducted additional nonclinical testing and successfully completed a Type C meeting with the U.S. Food and Drug Administration (FDA) in December supporting initiation of a 1-month safety study for bilateral and higher (0.64 mg) dosing of OTO-313. Additional efficacy results from the Phase 2 extended observation period and safety data from the bilateral and higher unilateral dose study are anticipated in the second half of 2022. Altogether, these multiple clinical data readouts for OTO-313 are expected to support an End-of-Phase 2 meeting with the FDA and inform the design of the Phase 3 clinical program planned to start in the first half of 2023.

They're sounding confident indeed! Great to hear that they're closely working with the FDA too while moving things along.

 

[ThomasRobert]

Can someone refresh my memory? OTO-313's (for tinnitus) compound is Gacyclidine. What is the mechanism of action for this drug? If this doesn't restore hair cells or synapses, how is this intended to quite tinnitus? Or to rephrase the question, this compound will do what to the damaged cochlea? The brain receives input from the cochlea, but once this input gets interrupted, tinnitus occurs (e.g., the brain trying to increase its volume trying to recover or cover up for the missing input).

1) What is Gacyclidine's job inside the cochlea? What is it going to do to these receptors?

2) How much Gacyclidine is able to pass through the Round Window?

3) Is there any evidence of Gacyclidine being able to reach the entire cochlea (regardless of their slow fusion gel)?

We are expecting Phase 2 results by June 2022.

 

[star-affinity]

@ThomasRobert, good questions that you can direct directly to Otonomy here:

https://investors.otonomy.com/investor-resources/contact-us

 

[Exit]

Can someone refresh my memory? OTO-313's (for tinnitus) compound is Gacyclidine. What is the mechanism of action for this drug? If this doesn't restore hair cells or synapses, how is this intended to quite tinnitus? Or to rephrase the question, this compound will do what to the damaged cochlea? The brain receives input from the cochlea, but once this input gets interrupted, tinnitus occurs (e.g., the brain trying to increase its volume trying to recover or cover up for the missing input).

1) What is Gacyclidine's job inside the cochlea? What is it going to do to these receptors?

2) How much Gacyclidine is able to pass through the Round Window?

3) Is there any evidence of Gacyclidine being able to reach the entire cochlea (regardless of their slow fusion gel)?

We are expecting Phase 2 results by June 2022.

I don't really know but I think it's a little like Trobalt. And that it's supposed to calm down the nerves firing...? Kind of like anti-seizure drugs?

Perhaps someone can confirm some of what I said...

 

[ThomasRobert]

I don't really know but I think it's a little like Trobalt. And that it's supposed to calm down the nerves firing...? Kind of like anti-seizure drugs?

Perhaps someone can confirm some of what I said...

Yes, and I wonder why tinnitus would be reduced by calming down the nerves if the input from the cochlea to the brain is still missing...

 

[xyz]

Yes, and I wonder why tinnitus would be reduced by calming down the nerves if the input from the cochlea to the brain is still missing...

I don't know how this Gacyclidine will work, but it's not a new compound. In this study 4 out of 6 experienced a temporary relief from tinnitus. Maybe Otonomy has created something that the temporary lasts a little longer.

 

[DimLeb]

@ThomasRobert, I might be all wrong, but probably the nerves and hair cells are still connected by some surviving synapses. The drug might be using some other pathway though, so maybe as long as the cochlea has the auditory nerve to the brain, it somehow works.

 

[Diesel]

Yes, and I wonder why tinnitus would be reduced by calming down the nerves if the input from the cochlea to the brain is still missing...

In one of their more recent webinars, Otonomy described that in the acute phase following a noise-induced trauma that resulted in tinnitus, the synapses/nerves in the cochlea are in a hyper-excited state. Over that acute period of time, this hyper-excitement results in the decay of the synaptic connection to the hair cell and/or death of the hair cell. Although, they seemed to think the decay of synaptic connection was more likely the case. What OTO-313 should be doing is dampening that hyper-excited state so that the synapses can recover and return to a 'normal' state, thereby reducing any chronic damage.

What I am speculating based on their description is that often we see new members with recent tinnitus as a result of a noise-induced insult to the cochlea describe their tinnitus as a loud "dentist drill" sound, or similar, which eventually calms down into something more static. My guess is that they experiencing this "acute period of hyperexcitability" until the synapses decay or cells die, and the brain is left with "chronic phantom-limb cochlea syndrome" when the tinnitus becomes permanent.

What Otonomy has claimed that remains open as undetermined is:

Are there cases of chronic hyperexcitability in tinnitus sufferers that OTO-313 might address?

They have said multiple times that they do not know if there is a therapeutic window for OTO-313, and the speciic scope of the patient population.

This would mean that there may be a spectrum of tinnitus from Acquired SNHL, where part of all of the tinnitus experienced by hyperexcitability that this drug may be able to normalize.

 

[InNeedOfHelp]

It would make sense that even though the drug targets the 'acute' phase, I can imagine it might still be able to deal with for example reactivity of tinnitus as well as spiking/worsening due to sound exposure? I don't think spikes are ever researched properly but if caused by sound it would make sense to be cochlear based... and the same for reactivity?

 

[GoatSheep]

They prefer acoustic traumas. Somatic just means you can modulate the tinnitus with head, neck, or other body movements.

I don't recommend OTO-313 at all, but especially if you are getting better naturally. I felt I was before too before I got it. In my desperation I made a stupid move, as I was already suffering at a level that couldn't afford to go much higher. Don't overestimate your ability to cope with worse tinnitus.

@ChrisBoyMonkey, how are you doing now?

 

[David S]

@ThomasRobert, I might be all wrong, but probably the nerves and hair cells are still connected by some surviving synapses. The drug might be using some other pathway though, so maybe as long as the cochlea has the auditory nerve to the brain, it somehow works.

Thomas, it is my belief that cochlea based tinnitus could be caused by mainly 2 tings.

Damaged inner hair cells (IHC) which leads to lost signal to the brain and brain based tinnitus as a result. More tonal tinnitus.

Or

Malfunction of the spontaneous synapses of the inner ear and the amplifying mechanism. Mainly related to damaged outer hair cells OTC. This type of tinnitus can stay cochlea based for a very long time. This is not a lost signal but a misfiring from the inner ear. This can also lead to reactive tinnitus and distortions.

I think I suffer from the latter. Quite troublesome unfortunately.

 

[kingsfan]

Is this drug going to even be useful to any of us in here? Are our labels already past the "sell by" date?

 

[GoatSheep]

Is this drug going to even be useful to any of us in here? Are our labels already past the "sell by" date?

@Diesel just addressed this a couple posts up:

What Otonomy has claimed that remains open as undetermined is:

Are there cases of chronic hyperexcitability in tinnitus sufferers that OTO-313 might address?

They have said multiple times that they do not know if there is a therapeutic window for OTO-313, and the speciic scope of the patient population.

This would mean that there may be a spectrum of tinnitus from Acquired SNHL, where part of all of the tinnitus experienced by hyperexcitability that this drug may be able to normalize.

 

[Gb3]

Otonomy Completes Enrollment in Phase 2 Clinical Trial of OTO-313 in Tinnitus

 

[Bambam0]

Otonomy Completes Enrollment in Phase 2 Clinical Trial of OTO-313 in Tinnitus

Juicy. Can't believe this thing is still at a $100m market cap. If the results are positive this is an easy 10 bagger.

 

[DimLeb]

Sorry if I didn't understand correctly. This means that they have just completed injecting patients, so now they have to wait for the 4 month follow-up of the last patient plus some time to collect/analyse the information? And then post the results?

 

[Toby1972]

Juicy. Can't believe this thing is still at a $100m market cap. If the results are positive this is an easy 10 bagger.

So here comes the stock market guru Bob again.

So if Otonomy succeeds, the stock could potentially triple at most.

The risk of everything going wrong is immensely higher.

As an example, let me mention the BioNTech share. When no one suspected that they were dealing with a pandemic and making the world's #1 vaccine, it multiplied tenfold. But now they are a cash cow and the price has been going downhill for months.

Your cancer medication isn't helping you. That would bring in only a fraction of the current profits.

Well, with Otonomy, if they bring OTO-313 onto the market, only the very, very badly affected, like us here, would want to take it.

With my 4/10 tinnitus until 2020, I would never have wasted a thought about having something injected through my eardrum. Never.

Therefore, commercialization will be very limited.

Unfortunately.

 

[NYCGuy]

Sorry if I didn't understand correctly. This means that they have just completed injecting patients, so now they have to wait for the 4 month follow-up of the last patient plus some time to collect/analyse the information? And then post the results?

I know people who started the trial several months ago, but I also have a friend who was one of the last ones to receive the injection and that was 1 month ago.

My friend mentioned that the doctor said he had high hopes and was seeing good results so far.

 

[Gb3]

@Toby1972, the injection into the ear is really no more painful than getting the vaccines.

 

[Sentinel]

Yeah, I've mentioned this but with the numbing cream, I literally couldn't feel it when I got the OTO-313 shot. He told me he was done and then we were done.

 

[AfroSnowman]

Yeah, I've mentioned this but with the numbing cream, I literally couldn't feel it when I got the OTO-313 shot. He told me he was done and then we were done.

Has your improvement continued or did you revert to baseline?

 

[Brian Newman]

Yeah I had an IT injection (not OTO-313), it's not bad. I still have a little pain in my eardrum. Worst was the numbing cream that stung a bit, when the needle went through, the room was spinning for a few seconds then that's it. Tinnitus was not really affected, it did get worse but I think it was from the 2 hour car ride back cause of my hyperacusis.

 

[Brian Newman]

So here comes the stock market guru Bob again.

So if Otonomy succeeds, the stock could potentially triple at most.

The risk of everything going wrong is immensely higher.

As an example, let me mention the BioNTech share. When no one suspected that they were dealing with a pandemic and making the world's #1 vaccine, it multiplied tenfold. But now they are a cash cow and the price has been going downhill for months.

Your cancer medication isn't helping you. That would bring in only a fraction of the current profits.

Well, with Otonomy, if they bring OTO-313 onto the market, only the very, very badly affected, like us here, would want to take it.

With my 4/10 tinnitus until 2020, I would never have wasted a thought about having something injected through my eardrum. Never.

Therefore, commercialization will be very limited.

Unfortunately.

I don't think this is the case, more than 2 million have severe tinnitus apparently in the US unless Google is lying.

Before all this crap happened to me, I would have gotten an IT shot when my tinnitus was like a 3 to be done with it forever.

And don't forget OTO-413 for hearing loss is an even bigger market.

Definitely no guarantee because if these drugs fail, the company is going under.

 

[Bambam0]

So if Otonomy succeeds, the stock could potentially triple at most.

WUT. This stock was worth triple 1 year ago.

 

[Eliot Martin]

FX-322 + FX-345 + OTO-313 + OTO-413 + NHPN-1010 = Tinnitus diminished + Hearing gain.

 

[Exit]

FX-322 + FX-345 + OTO-313 + OTO-413 + NHPN-1010 = Tinnitus diminished + Hearing gain.

Take them all and see what happens

 

[Nobody19]

WUT. This stock was worth triple 1 year ago.

Their Phase 3 trial for a Meniere drug failed.

About commercialization, I think quite some people who just have tinnitus might get this shot. It takes a while before habituation kicks in.

 

[Brian Newman]

FX-322 + FX-345 + OTO-313 + OTO-413 + NHPN-1010 = Tinnitus diminished + Hearing gain.

Hahah if only. Imagine.

 

[Toby1972]

@Toby1972, the injection into the ear is really no more painful than getting the vaccines.

I don't mean the process itself of piercing the eardrum, but having an injection that you don't know exactly, a process that would have to hit exactly the right area in the ear, something that we don't know the long-term effects of. I think only grade 3 and 4 (out of 4) patients would dare to do that.

 

[Exit]

I don't mean the process itself of piercing the eardrum, but having an injection that you don't know exactly, a process that would have to hit exactly the right area in the ear, something that we don't know the long-term effects of. I think only grade 3 and 4 (out of 4) patients would dare to do that.

If the ENTs got an incentive to push it to newcomers, I'm sure most will try after a month or two with no improvements on their own.