Sound Pharmaceuticals (SPI-5557 & SPI-1005)

[FGG]

Honestly this could be a godsend for hyperacusis and even noxacusis - the Johns Hopkins lab are exploring the role of cochlear inflammation (in addition to the Type 2s) on noxacusis. I can imagine setbacks also stemming from a chronically inflamed cochlea. Perhaps inflammation could also be why we tend to get spiked by non-noxious noise. This could be a gamechanger whilst we're waiting for the big guns to arrive (FX-322 etc).

I hesitated on whether or not to mention this because it hasn't gone through 3 phases of safety trials, but for anyone truly at the end of their rope (I would otherwise recommend not being a guinea pig without tons of your own research and cost/benefit analysis), this could be acquired in a similar way to how people were trying to get the Hough Pill for a fraction of that cost (but still a lot of money).

*** disclaimer: I have no idea how to tell if any of these labs are genuine or which ones would have good quality. Also, very few of us know how much inflammation we have in our cochleas and how much of that is contributing. But I know some people need any chance to get relief and it's a matter of literal life or death so I wanted to put that out there and let people make their own decisions.

Please know I'm not recommending this unless it's this or suicide because the drug will likely be available soon. But I do understand for some people "soon" might not be good enough so it might be worth a try for them.

 

[weab00]

Honestly this could be a godsend for hyperacusis and even noxacusis - the Johns Hopkins lab are exploring the role of cochlear inflammation (in addition to the Type 2s) on noxacusis. I can imagine setbacks also stemming from a chronically inflamed cochlea. Perhaps inflammation could also be why we tend to get spiked by non-noxious noise. This could be a gamechanger whilst we're waiting for the big guns to arrive (FX-322 etc).

Yes I'm excited as well and it's a lot closer than any other biotech right now.

 

[frpp]

If you are interested in trying this, you could ask them to apply for compassionate use.

Could you explain more about compassionate use? I'm not familiar with that term. Does it require a diagnosis?

 

[tommyd87]

Everything about this drug looks clean. Well tolerated, big net of diseases it could treat, solid clinical trial results, easy to consume (pill). From what I've read, the mechanism of Ebselen in SPI-1005 sounds like a glorified version of NAC for inducing Glutathione.

The points made here about COVID-19 are interesting. In theory, COVID-19 should help speed this along. I also find it interesting how little cochlear inflammation is discussed. There are so many discussions on hair cells and synapses, but cochlear inflammation could be very responsible for tinnitus and hyperacusis.

I wonder whether the report they released recently on the inflammation from noise was a key publication and they now have the required evidence to proceed further with human trials?

I still agree that the COVID-19 indication is surely going to assist in getting this released if it indeed has a benefit.

Furthermore I strongly believe that there will be benefit from treating the inflammation even if you had other treatments available like a synapse treatment for example.

 

[FGG]

Could you explain more about compassionate use? I'm not familiar with that term. Does it require a diagnosis?

It's also called Expanded access. Here is the Wikipedia about it:

https://en.m.wikipedia.org/wiki/Expanded_access

As to your question whether you need a diagnosis, I think you just a need an unambiguous description of a condition but I'm not sure about that. Your doctor should have access to the application and would be better suited to answer that.

 

[tommyd87]

I'm from the U.S.A.

I have a GP who would write me anything if I thought I needed it, no questions asked.

Ahh all good. Going by what you are saying, the rules for prescribing drugs are very different in America to what they are here in Australia. I wish it was that easy lol, although I am assuming a number of ear specialists will work with these sort of treatments and have no issues in prescribing them either. Essentially I suspect that this will be a novel and different area of treatment to what we have now and that even the doctors who work with this stuff will be somewhat looked upon with scorn at least initially.

 

[tommyd87]

The more I look into this drug, the more I believe Sound Pharmaceuticals really know this drug will be effective for many non-Ménière's patients as well.

This is an excerpt from their Phase 2b data release: "These improvements in auditory function further support the use of SPI-1005 to treat sudden idiopathic hearing loss, noise-induced hearing loss, and age-related loss where sensorineural hearing loss and tinnitus are prominent features."

The positioning for it to be used primarily for Ménière's is very strategic, as this is a market that has not been served. Moreover, I'm not aware of other companies or drugs that are close to treating this disease either. If we look at cochlear inflammation by itself, it stands to reason that many of us here may have a form of it to some degree. Leading audiologists and hearing specialists don't usually mention cochlear inflammation when hearing damage is present due to acoustic trauma or even ototoxicity. The focus is rather on hair cell loss as evidenced by audiometry testing.

Also, from Phase 2b: "Additionally, SPI-1005 treatment reduced tinnitus perception or tinnitus loudness (TL) by a statistically significant difference (p-value <0.05 using Fisher's Exact test) when compared to placebo. Reductions in TL averaged 1.4 pts in the 400 mg group vs 0.7 pts in the placebo group (30% reduction vs 10% reduction, p<0.02). These Phase 2b data confirmed an initial finding of the Phase 1b data, that SPI-1005 can lower tinnitus loudness by clinically relevant levels."

This drug works and is close to being accessible. I think we will be able to get our hands on it next year due to it also being tested to treat respiratory issues related to COVID-19. I predict strong benefit for a good deal of us here.

I reckon the major reason why it has taken so long to complete the required research and actual trials is because Sound Pharmaceuticals firstly want to get the treatment as good as they can possibly get it and secondly because they think that they have a winner treatment. The fact that this treatment can provide so much benefit to so many people and across multiple treatment areas indicates that they can hopefully expect good outcomes.

I think that while there has possibly been a delay in proceeding with trials for certain indications and subsequently getting the treatment released to the market, this won't have a negative outcome on the treatment overall. In fact I actually believe that this is a positive thing because it is obvious that Sound Pharmaceuticals clearly wants to demonstrate that this treatment is sound and robust. Research now verifies this.

Thus I think that this treatment is going to be brilliantly beneficial to anyone who has issues which will be assisted by any of the restorative treatments. The theory is that most of us probably do have cochlear inflammation of some kind and I think that SPI-1005 will wonderfully assist with treating this. Therefore I think that this will be a beneficial treatment to take regardless of what other drugs are available on the market to assist with ear issues.

 

[frpp]

Ahh all good. Going by what you are saying, the rules for prescribing drugs are very different in America to what they are here in Australia. I wish it was that easy lol, although I am assuming a number of ear specialists will work with these sort of treatments and have no issues in prescribing them either. Essentially I suspect that this will be a novel and different area of treatment to what we have now and that even the doctors who work with this stuff will be somewhat looked upon with scorn at least initially.

Sorry. What I meant is I have a GP who would prescribe things if I needed them, but I'm unsure if they are able to prescribe something that possibly only an ENT can.

However, if SPI-1005 gets approved for coronavirus then it would be easy to obtain.

 

[tommyd87]

Sorry. What I meant is I have a GP who would prescribe things if I needed them, but I'm unsure if they are able to prescribe something that possibly only an ENT can.

However, if SPI-1005 gets approved for coronavirus then it would be easy to obtain.

Yes, you are making more sense now. Not sure what the rules are for off-label prescriptions in America, however in Australia a medicine can only be prescribed by a doctor if it falls within their scope. So for example a GP could get away with prescribing a Viagra course for heart help (under the guise of erection issues) as treating this is considered to be within their scope. However, they couldn't probably prescribe SPI-1005 even for COVID-19 because COVID-19 here is considered a treatment that needs to be treated at a hospital. Incredibly even some fairly regular medications like eye drops can only be prescribed by either a hospital doctor or an eye specialist for example.

 

[Turgy]

Can this drug help with noise-induced tinnitus?

 

[Pitseleh]

Can this drug help with noise-induced tinnitus?

I guess one will have to try the drug and see if it brings an improvement for them.

 

[tommyd87]

Can this drug help with noise-induced tinnitus?

There is research indicating that it does help with noise induced hyperacusis and/or tinnitus. The thing is that you would obviously need to try it, although the evidence and the information suggests that noise induced issues would be treated with SPI-1005.

 

[weab00]

Can this drug help with noise-induced tinnitus?

I think it has a better chance of helping hyperacusis than tinnitus because hyperacusis has more to do inflammation.

 

[Diesel]

All, please excuse my ignorance re: SPI-1005 and Ebselen.

I've read a little this morning about how SPI-1005 seems to show significant improvements in Meniere's patients as it relates to tinnitus loudness. Is that what we're expecting to see in those with tinnitus symptoms from another cause?

I am not anywhere near as familiar with the tinnitus symptoms of Meniere's as I am to NIHL/SNHL. So, some explanation would help here.

 

[FGG]

All, please excuse my ignorance re: SPI-1005 and Ebselen.

I've read a little this morning about how SPI-1005 seems to show significant improvements in Meniere's patients as it relates to tinnitus loudness. Is that what we're expecting to see in those with tinnitus symptoms from another cause?

I am not anywhere near as familiar with the tinnitus symptoms of Meniere's as I am to NIHL/SNHL. So, some explanation would help here.

They are currently recruiting to prevent acute NIHL (similar to Hough Ear Institute's bomb blast pill). They have also shown pre-clinically to have an effect for Aminoglycosides ototoxicity.

How much it helps depends on how much inflammation and neuroinflammation you have.

The drug is very complex and appears to have the following effects:

Prevents some of the deleterious effects of glutamate.

Has an anti-oxidant, anti-inflammatory effect.

And is a reversible voltage gated calcium channel blocker.

My take is acutely, I think pretty much everyone if not everyone with cochlear injury will benefit, but chronically it would depend on how much inflammation and glutamate hyperexcitability effects you have. I suspect it will have at least some effect with many people and a great effect for others.

Sound seems to be pushing the glutathione perioxide induction effects so they see this as at least one of the primary effects they are interested in (has a high presence in the cochlea and the drug has good cochlear penetrance).

Other thoughts?

To add to this, since the above might not have answered your question @Diesel. It seems like the drug's effects on Meniere's are two fold: anti-inflammatory and vascular (calcium channel blockers can regulate blood pressure) perhaps working in synergy.

 

[tommyd87]

They are currently recruiting to prevent acute NIHL (similar to Hough Ear Institute's bomb blast pill). They have also shown pre-clinically to have an effect for Aminoglycosides ototoxicity.

How much it helps depends on how much inflammation and neuroinflammation you have.

The drug is very complex and appears to have the following effects:

Prevents some of the deleterious effects of glutamate.

Has an anti-oxidant, anti-inflammatory effect.

And is a reversible voltage gated calcium channel blocker.

My take is acutely, I think pretty much everyone if not everyone with cochlear injury will benefit, but chronically it would depend on how much inflammation and glutamate hyperexcitability effects you have. I suspect it will have at least some effect with many people and a great effect for others.

Sound seems to be pushing the glutathione perioxide induction effects so they see this as at least one of the primary effects they are interested in (has a high presence in the cochlea and the drug has good cochlear penetrance).

Other thoughts?

Do you think this could mean that with this treatment and also one of the other synapse treatments the Hough pill might become redundant?

 

[FGG]

Do you think this could mean that with this treatment and also one of the other synapse treatments the Hough pill might become redundant?

Maybe? Or they may even have synergistic effects. Who knows?

Hough is probably safer if you have certain conditions like hypotension but thus far Sound Pharmaceuticals hasn't shown any safety issues (but they probably didn't have patients with vascular insufficiency etc.).

 

[tommyd87]

Maybe? Or they may even have synergistic effects. Who knows?

Hough is probably safer if you have certain conditions like hypotension but thus far Sound Pharmaceuticals hasn't shown any safety issues (but they probably didn't have patients with vascular insufficiency etc.).

Interesting times ahead indeed.

 

[FGG]

Interesting times ahead indeed.

Because of the COVID-19 trials for this drug, I think we will get pretty good additional safety data soon as well as an anecdotal idea to what degree it might help the more chronic tinnitus cases. IE how many sufferers of tinnitus and to what extent are we dealing with things like inflammation and glutamate hyperexcitabilty on top of structural damage.

It's for sure individual/case by case but at least we could get more data.

 

[Pitseleh]

They are currently recruiting to prevent acute NIHL (similar to Hough Ear Institute's bomb blast pill). They have also shown pre-clinically to have an effect for Aminoglycosides ototoxicity.

How much it helps depends on how much inflammation and neuroinflammation you have.

The drug is very complex and appears to have the following effects:

Prevents some of the deleterious effects of glutamate.

Has an anti-oxidant, anti-inflammatory effect.

And is a reversible voltage gated calcium channel blocker.

My take is acutely, I think pretty much everyone if not everyone with cochlear injury will benefit, but chronically it would depend on how much inflammation and glutamate hyperexcitability effects you have. I suspect it will have at least some effect with many people and a great effect for others.

Sound seems to be pushing the glutathione perioxide induction effects so they see this as at least one of the primary effects they are interested in (has a high presence in the cochlea and the drug has good cochlear penetrance).

Other thoughts?

To add to this, since the above might not have answered your question @Diesel. It seems like the drug's effects on Meniere's are two fold: anti-inflammatory and vascular (calcium channel blockers can regulate blood pressure) perhaps working in synergy.

Related to glutamate, I imagine that would also help people with tinnitus who take benzos, allowing them to get more tinnitus relief while at the same time being able to taper gently.

 

[FGG]

Related to glutamate, I imagine that would also help people with tinnitus who take benzos, allowing them to get more tinnitus relief while at the same time being able to taper gently.

I had the same speculation but I was thinking more of the people who have increased tinnitus from tolerance/withdrawal. But no one knows (yet) of course.

 

[tommyd87]

Because of the COVID-19 trials for this drug, I think we will get pretty good additional safety data soon as well as an anecdotal idea to what degree it might help the more chronic tinnitus cases. IE how many sufferers of tinnitus and to what extent are we dealing with things like inflammation and glutamate hyperexcitabilty on top of structural damage.

It's for sure individual/case by case but at least we could get more data.

I absolutely agree with you that this is an individual/case by case scenario of how SPI-1005 benefits a patient. I do think there will be big benefits from SPI-1005 in many cases, even if it doesn't totally relieve someone's tinnitus for example. I would also be interested in seeing how well other ear treatments work when SPI-1005 is used beforehand. I am wondering whether other treatments will work better and also be easier to administer once the inflammation has been treated by SPI-1005.

COVID-19 benefits SPI-1005 greatly and in fact it is probably an unexpected benefit from an unfortunate outcome. Obviously this extra data/information will help greatly and as a result I really think that this will mean there is a great deal of clarity around its outcomes when it is inevitably released too.

 

[ASilverLight]

Genuine question. I know reactive tinnitus is a huge debate, but do you think - if it is hyperacusis - it is also due to lingering inflammation? If so, could SPI-1005 possibly help the reactivity?

 

[serendipity1996]

Genuine question. I know reactive tinnitus is a huge debate, but do you think - if it is hyperacusis - it is also due to lingering inflammation? If so, could SPI-1005 possibly help the reactivity?

I think this is a very reasonable possibility.

 

[weab00]

Genuine question. I know reactive tinnitus is a huge debate, but do you think - if it is hyperacusis - it is also due to lingering inflammation? If so, could SPI-1005 possibly help the reactivity?

I think that's the current theory. Type II afferent pain fibers became inflamed and send pain signals to the brain. The brain is trying to protect itself from further damage and uses pain as a distress signal without regard for its potential psychological effects. People generally heal over time because their ears become less inflamed over time, but can suffer setbacks from loud noises which reinflames the ears. At least that's my understanding of it.

Going off that explanation, I do think this has great potential to help loudness hyperacusis and noxacusis sufferers since cochlear inflammation plays a big part in the injury/re-injury process.

 

[ASilverLight]

Yeah, my issue is definitely not pain or even regular noise being too loud, but my issue is the severe reactivity/fluctuations of my tinnitus which are very hard to pinpoint, but are probably due to noise and neck issues.

I'd be okay if my tinnitus stayed at baseline, so if SPI-1005 could help with that I'd be okay until a real proven cure comes along.

I guess we'll see.

 

[100Hz]

Genuine question. I know reactive tinnitus is a huge debate, but do you think - if it is hyperacusis - it is also due to lingering inflammation? If so, could SPI-1005 possibly help the reactivity?

I hope in theory it could calm cochlear inflammation very quickly after a setback. What I don't think it will do though is stop the actual setbacks in the first place which would need cochlea regeneration drugs.

SPI-1005 could be a sort of 'setback bomb blast pill' in my mind.

If the after effects of a setback could be stopped with a pill then that could fix 95% of what noxacusis is and how it affects people in such a devastating way. Imagine being able to take a pill and carry on with life instead of having to go and isolate in silence and pain for weeks at a time.

 

[GBB]

I think how much inflammation you have will determine how beneficial it is but for some it could be a game changer, in others who have structural damage with little accompanying inflammation, less so.

This is once again an area where diagnostics need to catch up. I wish I took this acutely for sure.

Would it be fair to say if when you take prednisone, you see a large difference, then that's like an indicator that SPI-1005 would help, and likewise, if prednisone does not help, this would not do much? I ask because prednisone does basically nothing for me.

 

[FGG]

Would it be fair to say if when you take prednisone, you see a large difference, then that's like an indicator that SPI-1005 would help, and likewise, if prednisone does not help, this would not do much? I ask because prednisone does basically nothing for me.

I don't think so at all. They have very different mechanisms of action. If you have inflammation from immune cell recruitment and volume/pressure expansion Prednisone is more likely to help. SPI-1005 is better for glutamate hyperexcitabilty, oxidative stress etc.

Also, oral steroids don't have great cochlear penetrance (SPI-1005 is unique for an oral med in that it does) and intratympanic steroids apparently have a polarity problem which makes their cochlear penetrance highly variable.

In addition, inflammation is incredibly complex even when the cause is more clear. I can give you a veterinary example of what I mean:

IMHA is a condition in dogs (and cats) where the immune system destroys their red blood cells causing a severe anemia that may result in blood transfusions and death if not treated.

Some dogs respond to Prednisone others have no response and need Cyclosporine or Mycophenolate. This is despite the fact that the disease involves similar auto immunity and inflammation in each set of dogs.

 

[tommyd87]

I don't think so at all. They have very different mechanisms of action. If you have inflammation from immune cell recruitment and volume/pressure expansion Prednisone is more likely to help. SPI-1005 is better for glutamate hyperexcitabilty, oxidative stress etc.

Also, oral steroids don't have great cochlear penetrance (SPI-1005 is unique for an oral med in that it does) and intratympanic steroids apparently have a polarity problem which makes their cochlear penetrance highly variable.

In addition, inflammation is incredibly complex even when the cause is more clear. I can give you a veterinary example of what I mean:

IMHA is a condition in dogs (and cats) where the immune system destroys their red blood cells causing a severe anemia that may result in blood transfusions and death if not treated.

Some dogs respond to Prednisone others have no response and need Cyclosporine or Mycophenolate. This is despite the fact that the disease involves similar auto immunity and inflammation in each set of dogs.

This is reassuring and your treatment knowledge is first rate.