Otonomy OTO-313 — Treatment of Tinnitus

[Exit]

The extended study will test a group of patients with tinnitus from 6-12 months. That will answer our questions a little bit...

The results will be out in about a year...

 

[tommyd87]

Is 43% considered a good result?

Not that I'm pessimistic or anything

But if only 43% got an improvement and this is their ideal patient in the acute phase, does it really offer much hope to any long term sufferer which we all will be by the time this is released which they are less hopeful about it working for anyway?

I mean if Dr. Shore's trial reports back only 40% saw improvement, I would consider that pretty poor or is it different for drugs?

I think that there are three things you need to consider with the outcomes of this OTO-313 trial.

1. 43% gained benefit, which is positive. The trial did not consider any factors which might have influenced this result though such as their type of hearing loss or its level.

2. The acute phase is not considered to be Otonomy's ideal patient overall. It is simply the subset that they feel will be more able to get the medicine past through the clinical trial phases.

3. No determination can be made regarding long term sufferers because no trials have been conducted on this subset.

 

[AfroSnowman]

Is 43% considered a good result?

Not that I'm pessimistic or anything

But if only 43% got an improvement and this is their ideal patient in the acute phase, does it really offer much hope to any long term sufferer which we all will be by the time this is released which they are less hopeful about it working for anyway?

I mean if Dr. Shore's trial reports back only 40% saw improvement, I would consider that pretty poor or is it different for drugs?

I have often read experts talking about "cures" for tinnitus rather than a single silver bullet. If they can subtype who gets helped by this type of treatment then maybe this will be a meaningful treatment for some, but not all or even most of us.

 

[Wrfortiscue]

I have often read experts talking about "cures" for tinnitus rather than a single silver bullet. If they can subtype who gets helped by this type of treatment then maybe this will be a meaningful treatment for some, but not all or even most of us.

Better than nothing for now.

 

[lymebite]

Is 43% considered a good result?

While I do not know the answer to this, it brings to mind something a medical doctor said to me, regarding medications:

"a general rule of thumb is that a given medication will help about 30 percent of patients, and for those 30 percent that are helped, it will help their symptoms about 30 percent."

When I consider patient comments on various discussion sites about classes of meds such as benzodiazepines, anticonvulsants, antidepressants, etc. that 30 percent / 30 percent rule of thumb feels somewhere in the ballpark to me. Patients try meds, some say they are poison, some say they do nothing, and others say they help.

 

[tommyd87]

While I do not know the answer to this, it brings to mind something a medical doctor said to me, regarding medications:

"a general rule of thumb is that a given medication will help about 30 percent of patients, and for those 30 percent that are helped, it will help their symptoms about 30 percent."

When I consider patient comments on various discussion sites about classes of meds such as benzodiazepines, anticonvulsants, antidepressants, etc. that 30 percent / 30 percent rule of thumb feels somewhere in the ballpark to me. Patients try meds, some say they are poison, some say they do nothing, and others say they help.

This is quite questionable though as a lot of people are helped by medications like penicillin etc and the success rate would be also significantly greater than 30% as well.

 

[ColinUK]

It is always strange with these trial designs, I mean why not start with shotgun approach and start to see different groups to get an idea of who it's helping and then narrow it down. Surely that would save a lot of time. Could be that it works not quite as expected but with such narrow starting point we may never find out.

 

[tommyd87]

It is always strange with these trial designs, I mean why not start with shotgun approach and start to see different groups to get an idea of who it's helping and then narrow it down. Surely that would save a lot of time. Could be that it works not quite as expected but with such narrow starting point we may never find out.

Taking that type of approach leads to problems getting things passed/approved by the FDA. From what we have seen thus far, the FDA requires very specific and very narrow criteria to be met in order for a medicine to go through a clinical trial. This includes trialling a set dose size on a specific category of people.

Thus the best way for a firm like Hough Ear Institute or Otonomy to deal with this is to put it through by testing the subset that is likely to have the best results from it in the trial process and then test it off label once the medicine has been passed, as there are no restrictions on who can take it.

 

[Toby1972]

2025...?

OTIC is up from $1.1 to $2 without any news

You mean $1.1 to $1.2? Maybe because the German stock market guru Bobb has made an investment?

 

[Exit]

You mean $1.1 to $1.2? Maybe because the German stock market guru Bobb has made an investment?

I think that Bobb guru needs to invest in new glasses

 

[Bob1234]

1. 43% gained benefit, which is positive. The trial did not consider any factors which might have influenced this result though such as their type of hearing loss or its level.

13% of the placebo group gained a benefit by healing naturally. Definitely showing some promise.

Only 31 patients though, so it's really hard to draw any definitive conclusions...

 

[Nobody19]

Is 43% considered a good result?

Not that I'm pessimistic or anything

But if only 43% got an improvement and this is their ideal patient in the acute phase, does it really offer much hope to any long term sufferer which we all will be by the time this is released which they are less hopeful about it working for anyway?

I mean if Dr. Shore's trial reports back only 40% saw improvement, I would consider that pretty poor or is it different for drugs?

I've just read the paper. 43% showed an improvement of at least 13 points on TFI. 21% even had an improvement of 30 points, but that data isn't statistically strong enough.

If I understand the paper correctly, 1/3 of treated patients showed no improvement in symptoms compared to 62;5% of those treated with placebo.

 

[Paulmanlike]

These results look like very familiar with the TinniTool I bought years ago for £300. It had a little leaflet with it off this small Italian study showing the efficacy of it. Just like Lenire. Just like ACRN.

Not impressed by the slightest. Neither is the stock market.

I've followed research for years.

Sorry for sounding pessimistic but I really can't get an erection over this.

 

[Wrfortiscue]

These results look like very familiar with the TinniTool I bought years ago for £300. It had a little leaflet with it off this small Italian study showing the efficacy of it. Just like Lenire. Just like ACRN.

Not impressed by the slightest. Neither is the stock market.

I've followed research for years.

Sorry for sounding pessimistic but I really can't get an erection over this.

So what you're saying is... we are still screwed.

 

[patorjk]

I've just read the paper. 43% showed an improvement of at least 13 points on TFI. 21% even had an improvement of 30 points, but that data isn't statistically strong enough.

View attachment 47212

If I understand the paper correctly, 1/3 of treated patients showed no improvement in symptoms compared to 62;5% of those treated with placebo.

I believe those graphs show data for patients that had a particular point improvement at both weeks 4 and 8. However, it looks like many patients continued improving. If you look at the 4 case studies Otonomy talks about in their corporate presentation, at least 4 responders had improvements greater than 35 points at week 8:

In most cases it looks like patients are continuing to improve, and worst case it doesn't look like the improvement is fading any. In Phase 2 they're measuring out until week 16, so it'll be interesting to see what kind of data they get from the longer time frame.

As an aside, they wanted to up the dose of the drug for the Phase 2 study, but the FDA wouldn't let them without re-doing Phase 1. I imagine if they make it to market they'll do a quick Phase 1 for a stronger version of the drug. So I suspect if this is successful there will be an "extra strength" version not too long after the initial version.

Not impressed by the slightest. Neither is the stock market.

The stock has bounced up ~60% in the last 2 months and there won't be any big news until next summer. Dr. Weber addressed the drop that happened mid-summer in one of the recent investor conferences, stating that he believed it was because there wasn't any news due for a year or so. I tend to agree with this. I think we'll get a clearer picture of what people think next Spring, though things will be muddled a bit because they have 2 trials ending, and OTO-413 is arguably more impactful.

 

[Nobody19]

I believe those graphs show data for patients that had a particular point improvement at both weeks 4 and 8. However, it looks like many patients continued improving. If you look at the 4 case studies Otonomy talks about in their corporate presentation, at least 4 responders had improvements greater than 35 points at week 8:

View attachment 47213

In most cases it looks like patients are continuing to improve, and worst case it doesn't look like the improvement is fading any. In Phase 2 they're measuring out until week 16, so it'll be interesting to see what kind of data they get from the longer time frame.

That's great to hear! Do we know if those improvements are statistically significant?

 

[UHPTS]

I believe those graphs show data for patients that had a particular point improvement at both weeks 4 and 8. However, it looks like many patients continued improving. If you look at the 4 case studies Otonomy talks about in their corporate presentation, at least 4 responders had improvements greater than 35 points at week 8:

View attachment 47213

In most cases it looks like patients are continuing to improve, and worst case it doesn't look like the improvement is fading any. In Phase 2 they're measuring out until week 16, so it'll be interesting to see what kind of data they get from the longer time frame.

As an aside, they wanted to up the dose of the drug for the Phase 2 study, but the FDA wouldn't let them without re-doing Phase 1. I imagine if they make it to market they'll do a quick Phase 1 for a stronger version of the drug. So I suspect if this is successful there will be an "extra strength" version not too long after the initial version.

The stock has bounced up ~60% in the last 2 months and there won't be any big news until next summer. Dr. Weber addressed the drop that happened mid-summer in one of the recent investor conferences, stating that he believed it was because there wasn't any news due for a year or so. I tend to agree with this. I think we'll get a clearer picture of what people think next Spring, though things will be muddled a bit because they have 2 trials ending, and OTO-413 is arguably more impactful.

Thanks for your summary. From how it was presented before I had a feeling that the improvements of the drug were marginal. Those graphs show that the drug has its super responders. Even though if it was just let's say 10% of all patients that respond so well, it would still mean that the drug works. I don't recall of any other drug or treatment to have this effect and be able to keep it permanently.

 

[patorjk]

That's great to hear! Do we know if those improvements are statistically significant?

Unless there was a bunch of placebo patients who suddenly had a big jump up at week 8, I would assume so. However, they didn't specifically report on this stat nor is the study goal based around just the week 8 measure (though looking at the graphs I do think it's compelling).

I think the reason they made the primary outcome measure for this study and their new Phase 2 study a sustained improvement at weeks 4 and 8 is to dampen any impact seen by the placebo effect. It's more unlikely that the placebo effect will sustain itself across 2 measurement points - at least in a significant way. They're doing the same thing for their OTO-413 study.

Another important point - if you look at the other charts in their corporate presentation, specifically slides 8 and 11, you'll see TFI improvement was significantly better for patients with a higher baseline and for patients who had had tinnitus for at least 3-6 months (in Phase 1, they only looked at patients who'd had tinnitus for less than 6 months). They've used this data to refine the entry requirements. In one of the investor conferences I listened to they said that for Phase 2 patients now have to have had tinnitus for at least 2 months to qualify (they've also barred severe hearing loss patients - who apparently didn't see much benefit). With these changes, we may see data that looks more compelling, though time will tell.

 

[Joeseph Stope]

Intratympanic treatment for tinnitus: A review

The above link is to give everyone some perspective on the background history in the present thrust of research. The compiler of the research tells us that the intratympanic approach to tinnitus goes right back to the 1940s in Kansas.

It makes good reading especially for the un-initiated such as yours truly.

I had assumed that the trailblazers of intratympanic injections were outfits such as Otonomy, Frequency Therapeutics, Hough Ear Institute or Pipeline Therapeutics. Well I'm sure they are or hope that they are in their own way.

It's sobering to think that the first attempt was way back during the Second World War. Your grand-dad's time so-to- speak.

So the "value-added" of the present wave is the tinkering with the "small molecules" -- the bio-pharmaceutical agent, and the delivery agent -- gel or whatever.

Things move slowly in the Otology/Audiology world

 

[Kenilworth]

I wonder how OTO-313 and RL-81 combined would work for tinnitus? Maybe the combination may completely cure tinnitus?

I'm just glad something is happening within this decade. Research is very slow and some of us are having it bad, but there's something to be optimistic about and hold on to, at least. I believe Phase 2 results for OTO-313 may be more compelling or interesting in such a way that we will know who exactly the drug works for. It may work for anyone (acute or chronic). But it may not, however, work for everyone.

 

[tommyd87]

Intratympanic treatment for tinnitus: A review

The above link is to give everyone some perspective on the background history in the present thrust of research. The compiler of the research tells us that the intratympanic approach to tinnitus goes right back to the 1940s in Kansas.

It makes good reading especially for the un-initiated such as yours truly.

I had assumed that the trailblazers of intratympanic injections were outfits such as Otonomy, Frequency Therapeutics, Hough Ear Institute or Pipeline Therapeutics. Well I'm sure they are or hope that they are in their own way.

It's sobering to think that the first attempt was way back during the Second World War. Your grand-dad's time so-to- speak.

So the "value-added" of the present wave is the tinkering with the "small molecules" -- the bio-pharmaceutical agent, and the delivery agent -- gel or whatever.

Things move slowly in the Otology/Audiology world

This is not the first time that there has been a treatment trialled a significantly long time ago which has not progressed further for a number of years too. The difference is that there's tonnes of progression in terms of medicine development and research techniques since then.

I wonder how OTO-313 and RL-81 combined would work for tinnitus? Maybe the combination may completely cure tinnitus?

I'm just glad something is happening within this decade. Research is very slow and some of us are having it bad, but there's something to be optimistic about and hold on to, at least. I believe Phase 2 results for OTO-313 may be more compelling or interesting in such a way that we will know who exactly the drug works for. It may work for anyone (acute or chronic). But it may not, however, work for everyone.

RL-81 is a suppressor from what I believe. It doesn't actually eliminate it in the same manner as some researchers have hypothesised would happen with treatment types like hearing regeneration.

Therefore you will need to take the RL-81 medicine regularly in the same manner as people take tablets for their heart conditions or cholesterol.

 

[Wrfortiscue]

Does the intratympanic injection hurt?

 

[Aleksandar]

Does the intratympanic injection hurt?

Not too much...

 

[PortugalTheMan]

Let's not fire rockets ahead of time

But if tinnitus originates in the cochlea, OTO-313 can be the solution and our relief.

If tinnitus originates in the brain, it won't help.

Let's endure this suffering another 5 years, so we can have some relief.

 

[Exit]

Does the intratympanic injection hurt?

About the same as a needle in the balls

 

[Nobody19]

Maybe the combination may completely cure tinnitus?

Don't hope for a cure too fast. Medicine is bad at curing things.

It would be great if we actually had something that improved our symptoms.

 

[tommyd87]

Let's not fire rockets ahead of time

But if tinnitus originates in the cochlea, OTO-313 can be the solution and our relief.

If tinnitus originates in the brain, it won't help.

Let's endure this suffering another 5 years, so we can have some relief.

This debate has been had before but basically there is not much debate as to where it comes from (brain) but the debate is around whether it is initiated by a brain issue or an ear issue.

It is the thought from many that ear issues are what causes tinnitus.

 

[Lucifer]

Don't hope for a cure too fast. Medicine is bad at curing things.

It would be great if we actually had something that improved our symptoms.

Even though OTO-313 doesn't regrow hair cells or synapses we may need it combined with FX-322 to get rid of tinnitus permanently.

 

[Kenilworth]

Even though OTO-313 doesn't regrow hair cells or synapses we may need it combined with FX-322 to get rid of tinnitus permanently.

It may be the case. But does curing tinnitus mean complete silence? Assuming there will be a cure.

I was once told by my doctor that we all have tinnitus in some form and some have to be in a really really quiet space or Orfield Labs to hear it. So I reckon even if scientists do make a breakthrough in hearing regenerating or develop a cure, the tinnitus may still be around but we may not hear it even if we wanted to.

Just a thought.

 

[tommyd87]

Don't hope for a cure too fast. Medicine is bad at curing things.

It would be great if we actually had something that improved our symptoms.

If something worked only to suppress the symptoms then I think that this would be a real win and most people would be satisfied with that irrespective of whether or not other treatments come about.