Sound Pharmaceuticals (SPI-5557 & SPI-1005)

I haven’t found the mechanism of action on their drugs but within their tech page they are talking about p27Kip1 that apparently does signal cochlear hear cells and supporting cells to regenerate. They also claim that p27Kip1 is responsible of regeneration of some other tissues as well.

With Meniere’s there is sometimes some sort of fluid buildup in the inner ear and it may rupture one of the membranes. I guess that is what causes vertigo and hearing suppression. Now, for some the rupture does not happen and that is why not all Meniere’s sufferers have permanent side effects, just when the attacks happen.

 

Just an interesting find. One of Sound Pharmaceuticals’ advisors is a former Nobel Prize winner for Physiology and Medicine.

Wikipedia: Bruce Beutler

In fact. Their entire team is quite impressive.

Sound Pharmaceuticals' Team

This one has ‘fast track’ so 60% chance of getting to market.

I can’t find anything that suggests that the tinnitus experienced by Meniere’s patients is a low tone that corresponds to low frequency hearing loss.

The symptom is generally described as being like every other type of tinnitus.

30% reduction in loudness sounds good vs 10% placebo.

Put this treatment together with Dr. Shore’s device and we might have a significant loudness reduction.

 

Was it 30% response rate or 30% reduction in symptoms?

I thought the former was indicated.

 

If it helps by regeneration then it should treat hyperacusis and noxacusis too. It's gonna be so amazing when one of these drugs finally hits the market.

 

What do you think might be a reasonable time to estimate this to come to market (presuming the Phase 3 is successful)?

Even though this trial is for Meniere's, hearing loss sufferers may still be able to acquire this drug if it hits the market?

 

Googling makes it seem like it could take one to four years.

 

30% reduction in tinnitus loudness vs 10% of that in placebo.

 

The clinical trial is 1 year. Fast track NDA 6 months. Guess is 20-24 months.

 

Question is if the mechanism of tinnitus generation is the same in Meniere's as with the other types. I think in Meniere's there is fluid retention in the inner ear, which may suggest mechanical origin of tinnitus. In this case it may not work for other subtypes of tinnitus.

 

The compound is a potent anti-inflammatory so it treats inflammation, hence the hope it might help general tinnitus.

 

Hard to say because it’s not like Ménière’s patients don’t also have SSNHL, and tinnitus from that. I’m endlessly unclear if those with Ménière’s experience tinnitus in isolation of other symptom onset (such as SSNHL). If that’s the case, then yes, maybe fluid build-up alone would cause (temporary?) tinnitus due to pressure put on the nerves.

 

Look, if you go to their website, you will find they are targeting NIHL and associated tinnitus with SP-1005. This is in addition to Meniere's Disease.

Their drug does not working on reducing fluid in the ear.

It is a potent anti-inflammatory, not a diuretic.

 

@Padraigh Griffin, you are a breath of fresh air. Someone who knows what they are talking about!

 

Not to get too off topic but wouldn't an anti-inflammatory also work to reduce excess fluid? If not, why does Prednisone work so well with Meniere's patients?

 

Taking a break from this thread now too until there is new information to post.

Why negativity?

SPI-1005 is targeting both Meniere's and NIHL.

It has reduced tinnitus loudness 30% (treatment group) vs 10% (placebo) in Meniere's trials. This is one of the few trials that has reduced tinnitus volume and is placebo controlled.

It is an extremely potent anti-inflammatory.

There is good evidence that it may help tinnitus.

Let us hope.

 

From what I understand, SPI-1005 will most likely not be able to help us with our current tinnitus by the time it is out but only with future worsenings. It is to be used in the acute phase similarly to steroids. Did I get this right?

 

Just a quick google and click makes it seem like it can at least reduce the loudness and perception. Which is good, seeing as it's a very powerful anti-inflammatory and inflammation is part of what causes problems for hearing loss and tinnitus. It's not a silver bullet but it's promising. It should help a lot of people if it doesn't help everyone.

 

It has shown to do that for Meniere's disease, where both tinnitus and hearing loss can fluctuate over time due to fluid buildup. It doesn't seem clear to me how it could permanently improve tinnitus caused by other factors.

In regards to NIHL for example, the Ebselen trial specifically mentions treatment of "acute" hearing loss, which seems to indicate that it would mostly be useful in the prevention / early treatment of NIHL by reducing inflammation. As @Padraigh Griffin rightfully notes, it's a powerful anti-inflammatory. I don't see anything about it being a regenerative medication.

As you say however, hopefully it can at least reduce loudness and perception. Even if it does manage that, the question also remains as to whether long-term use of SPI-1005 is possible/advisable.

On another note, I was looking at Sound Pharmaceuticals' current trials and found out they're running one on Ebselen as an add-on treatment to antidepressants. The study's happening in the UK. Maybe some depressed british TTers could try to apply and score some advance Ebselen!

IMPase in Treatment-resistant Depression (OxIMP)

 

Even if it only helps a certain amount, which seems to be the case most of the time, it would be a great help for a lot of people.

Does anyone have a copy of the full text of the last study? I can't access it online.

 

Nice find!

I sent them a mail. I'm in Ireland but would be ok travelling if they let me. I did stop my antidepressants recently though so I probably wouldn't be eligible. Even though I started a week back on them again. Would be great to get on that trial. I think it would be really helpful for hyperacusis since that seems to be more inflammation than even tinnitus.

 

I recall reading that part of hearing loss is understood to be caused by poor blood flow to the inner ear. If Ebselen can aid blood flow into the ears, perhaps a follow up intravenous treatment of BDNF could aid in the repair of damaged tissue in the inner ear. The body is able to produce its own BDNF so it could do that on its own.

 

It may be useful looking at what it's been tested on to do:

1) Reduce tinnitus in Meniere's patients
2) Reduce NIHL and thereby associated tinnitus in ACUTE settings.

Due to its anti-inflammatory properties SPI-1005 would be similar to steroids.

I have not seen any evidence that it is useful for chronic hearing loss or tinnitus at all...

Of course I would like to be wrong, however I cannot find any evidence at all.

 

Otonomy already tried a steroidal treatment for Meniere's and it failed miserably.

 

I think what @Nick47 meant is that SPI-1005 would be used in a similar timeframe to how steroids are used right now. So shortly after NIHL trauma. I don't think SPI-1005 has the same method of action as steroids.

 

I agree, I don't think this is a steroid.

 

Looking at applying for this study, however, the MRI worries me. Is it the noisy inner ear one?

 

Really can’t be bothered, but if finding ‘evidence’ to satisfy yourself that it won’t help tinnitus floats your both then fair enough.

For me the fact it has reduced ‘tinnitus’ at all, irrespective of the test cohort being Meniere’s patients, is the best evidence of any drug reducing ‘tinnitus’ ever in a placebo controlled clinical trial.

It is not a steroid so stop comparing it to steroids. It is a compound administered for at least 28 days that is focused on reducing neuroinflammation.

There are lots of people who feel tinnitus is produced by inflammation.

Also, just to point out that there are a lot of ‘hummers’ on this forum, including myself. Low frequency tinnitus. I also don’t have Meniere’s but am down more than 30 dB in the low frequencies.

However, I really think reducing inflammation will help lots of tinnitus sufferers.

Honestly, I really don’t want to engage with you anymore due to your negativity. Good luck with your tinnitus journey. Take that in a friendly way.

I’m in such a delicate state I’d prefer optimistic (yet rationally so) posts.

 

@Padraigh Griffin, this was not directed at you. It was a point made on the study design and outcomes. It was not negative or positive but factual. I looked at the studies, what they measured ,and the outcomes of the study. This led to the conclusions. That is science.

Of course I hope it benefits many chronic tinnitus patients, that would be fantastic.

My comparison with steroids was not in similar mechanism of action, but instead outcome, due to its anti-inflammatory action.

@CRGC, thank you for the link to the study on depression. All I can say is yesterday I emailed the researchers and expressed an interest.

The MRI worries me, as it does many, because my tinnitus has been very reactive since February. I think it's the brain MRI which is 'less' noisey. If accepted, I would be looking at suitable protection. It is a 250 mile round trip too.

 

From the 46th Annual MidWinter Meeting of Association for Research in Otolaryngology (ARO):

Ebselen Attenuates Noise-Induced Tinnitus in Mice

Results: Three months after noise-exposure, permanent threshold shifts were observed in the open ear of all noise-exposed mice across the three tested frequencies (8-20 KHz). Cochlear histology revealed extensive IHCs and OHCs damage and loss in the open ear vs the closed ear. GPIAS showed behavioral evidence of NIT in 6 out of 27 noise-exposed mice. After 4 days of ebselen treatment in these six NIT mice, gap detection deficits were significantly reduced to pre-exposure levels. This reduction reversed over time, and the gap detection deficits returned to pre-treatment levels one week after treatment.

Conclusions: A 4-day course of ebselen treatment can temporarily reverse gap detection deficits to baseline, pre-noise levels in mice that developed NIT. This work is the first demonstration of an anti-inflammatory reversing NIT after the development of NIHL where OHC and IHC loss was significant. Longer treatment durations are being tested to determine if this reversal can be permanent and results in the repair of injured hair cells. These data provide promising implications for ebselen as a treatment for noise-induced tinnitus in adult humans.

 

And if you have had chronic tinnitus for some years, how will Ebselen help? Or is there even a possibility for it to help in such cases?