Sound Pharmaceuticals (SPI-5557 & SPI-1005)

[Croaker]

Ok, this is what Sound Pharmaceuticals says ebselen (SPI-1005) does:
"SPI-1005, a proprietary oral formulation of ebselen, is a small molecule mimic and inducer of glutathione peroxidase (GPx). GPx is the dominant catalytic antioxidant enzyme in the cochlea and is critical for auditory function.

Endogenous GPx reduces reactive oxygen and nitrogen species by first binding them to selenocysteine then reducing the selenic acid intermediate through a reduction with glutathione (GSH). SPI-1005 mimics the catalytic activity of GPx1 by utilizing a bound selenonitryl moiety at its active site and see cycling with GSH or other thiols. Therefore, ebselen functions catalytically, and is redox sensitive. This efficient mechanism of action allows SPI-1005 to work at low oral doses, unlike antioxidants such as n-acetylcysteine. During the in vivo metabolism of SPI-1005, the selenium moiety is retained and is not bioavailable.

In addition to functioning as a GPx mimic and inducer, ebselen has been shown to reduce cytochrome-C release from mitochondria and nuclear damage during lipid peroxidation, and is effective in preventing neuronal apoptosis and reducing tissue inflammation associated with traumatic injury."

Most of this goes over my head but I get a couple important things from this. This is not glorified NAC since they specifically say it's good at getting to the cochlea orally. Most of what it does seems to be relevant only to recent events UNLESS H really does come down to the chronic presence of free radicals. Or whatever cytochrome-C release is.

The last sentence about tissue inflammation is confusing because they point it out separately from the rest of the molecule's functions. Does this imply that they know it helps with general inflammation but they don't understand the mechanism behind it?

 

[100Hz]

Where do you think this ATP is coming from? I thought it only happened upon initial cell death. Unless damaged yet still living cells are doing it. In which case no upcoming medication would solve the problem unless SPI-1005 can clean ATP up as part of its antioxidant effects?

The 2 things that I can't ignore is how obvious it is that raw noise at certain frequencies causes my setbacks, and that we have nociceptors in the cochlea that respond to ATP. To me those are facts.

Your question above, is the burning question though, where does the ATP come from? If it's coming from dead OHC support cells upon repeat exposure to significant noise at the corresponding frequency then that would be good for hair cell regeneration I think. The fact that setbacks do seem to be frequency specific makes me more convinced that this is the case.

If the ATP is coming from somewhere else, either entirely or in addition to support cells then that could be a problem if its down to damage that FX-322 is not designed to fix (in other words FX-322 would only fix part of the ATP release problem). I'm assuming that Type II afferents stay sensitized even once hair cells are regenerated and so ATP leak from anywhere else in the cochlea would potential continue to stimulate them. I think it's less likely though. Whatever the case I think that where setbacks are concerned they are caused by ATP release fundamentally as a result of noise. I don't think ATP gets released at random, otherwise you'd get setbacks even with no noise exposure, I don't think I've heard of that happening.

If FX-322 failed to stop all ATP leakage (no matter what it did successfully fix), and SPI-1005 can tackle cochlear inflammation then I don't see why it couldn't be taken after each setback. It's not ideal because the underlying problem (ATP release from who knows where) still exists, but it would stop the setback symptoms which are by the far the most crippling part of noxacusis.

I think of noxacusis as a susceptibility to setbacks in a similar way an asthma suffer is susceptible to asthma attacks. An asthma sufferer quickly negates the effects of an attack with an asthma drug. We would do the same with SPI-1005?

 

[Croaker]

I think of noxacusis as a susceptibility to setbacks in a similar way an asthma suffer is susceptible to asthma attacks. An asthma sufferer quickly negates the effects of an attack with an asthma drug. We would do the same with SPI-1005?

I hope so. That would be ideal. A lot of this makes sense intuitively but we just don't know enough to confirm it. Hyperacusis improves with long periods of rest so something must be going on that calms down over time. Logically that would be some irritant in the cochlea, and SPI-1005 seems to cover most of the options for that... in their own words "GPx is the dominant catalytic antioxidant enzyme in the cochlea." I really really hope that the drug does well in these COVID-19 trials.

 

[weab00]

The 2 things that I can't ignore is how obvious it is that raw noise at certain frequencies causes my setbacks, and that we have nociceptors in the cochlea that respond to ATP. To me those are facts.

Your question above, is the burning question though, where does the ATP come from? If it's coming from dead OHC support cells upon repeat exposure to significant noise at the corresponding frequency then that would be good for hair cell regeneration I think. The fact that setbacks do seem to be frequency specific makes me more convinced that this is the case.

If the ATP is coming from somewhere else, either entirely or in addition to support cells then that could be a problem if its down to damage that FX-322 is not designed to fix (in other words FX-322 would only fix part of the ATP release problem). I'm assuming that Type II afferents stay sensitized even once hair cells are regenerated and so ATP leak from anywhere else in the cochlea would potential continue to stimulate them. I think it's less likely though. Whatever the case I think that where setbacks are concerned they are caused by ATP release fundamentally as a result of noise. I don't think ATP gets released at random, otherwise you'd get setbacks even with no noise exposure, I don't think I've heard of that happening.

If FX-322 failed to stop all ATP leakage (no matter what it did successfully fix), and SPI-1005 can tackle cochlear inflammation then I don't see why it couldn't be taken after each setback. It's not ideal because the underlying problem (ATP release from who knows where) still exists, but it would stop the setback symptoms which are by the far the most crippling part of noxacusis.

I think of noxacusis as a susceptibility to setbacks in a similar way an asthma suffer is susceptible to asthma attacks. An asthma sufferer quickly negates the effects of an attack with an asthma drug. We would do the same with SPI-1005?

Do you think that SPI-1005 could instantly put us in the remission phase? Not to say that it can't be reaggrivated, but so as long as we're careful around noise then we can live relatively normal lives barring acoustic trauma outside of our control.

 

[Croaker]

Do you think that SPI-1005 could instantly put us in the remission phase? Not to say that it can't be reaggrivated, but so as long as we're careful around noise then we can live relatively normal lives barring acoustic trauma outside of our control.

The only data we have to go on is the phase 2 Meniere's trial. Its effect was not immediate in that trial, but it was well tolerated with no serious side effects. Symptoms were slowly reduced over the multiple weeks of the trial. So, I imagine it would be something we would take every day (400mg like in the trial) as a precaution against setbacks. Assuming it works.

 

[tommyd87]

The only data we have to go on is the phase 2 Meniere's trial. Its effect was not immediate in that trial, but it was well tolerated with no serious side effects. Symptoms were slowly reduced over the multiple weeks of the trial. So, I imagine it would be something we would take every day (400mg like in the trial) as a precaution against setbacks. Assuming it works.

There was the lab rat research trial for SPI-1005's tinnitus/hearing loss indication. This research apparently demonstrated fairly positive results as well. I actually believe that Sound Pharmaceuticals may utilise this report to indicate the treatment's benefit and effectiveness for tinnitus/hearing loss should it be approved for COVID-19 and then end up getting prescribed off-label for the other indications.

 

[weab00]

The only data we have to go on is the phase 2 Meniere's trial. Its effect was not immediate in that trial, but it was well tolerated with no serious side effects. Symptoms were slowly reduced over the multiple weeks of the trial. So, I imagine it would be something we would take every day (400mg like in the trial) as a precaution against setbacks. Assuming it works.

I definitely wouldn't mind taking this everyday for the rest of my life to prevent setbacks. Hopefully it's not too expsnsive.

 

[lapidus]

There was the lab rat research trial for SPI-1005's tinnitus/hearing loss indication. This research apparently demonstrated fairly positive results as well.

You mean this one?
https://www.frontiersin.org/articles/10.3389/fnins.2020.561185/full
It looked at tinnitus/hyperacusis and not hearing loss I think.

 

[tommyd87]

I definitely wouldn't mind taking this everyday for the rest of my life to prevent setbacks. Hopefully it's not too expsnsive.

I don't think that you would actually need to take this everyday to prevent setbacks though. I would actually assume you take this once and theoretically it should reduce symptoms and you wouldn't need to take it again. I also think that the medicine which treats the underlying causes like synapse medicines may also alleviate a lot of the issues too.

 

[tommyd87]

You mean this one?
https://www.frontiersin.org/articles/10.3389/fnins.2020.561185/full
It looked at tinnitus/hyperacusis and not hearing loss I think.

Yes I think it predominately does work to treat hyperacusis/tinnitus. Though there was some benefit offered for hearing loss too and it is apparently also the offical indication it is to be used for.

 

[Born To Slay]

Yes I think it predominately does work to treat hyperacusis/tinnitus. Though there was some benefit offered for hearing loss too and it is apparently also the offical indication it is to be used for.

I do have hearing loss but if this drug put a real dent in my hyperacusis and tinnitus, I wouldn't give a fuck about it.

 

[tommyd87]

I do have hearing loss but if this drug put a real dent in my hyperacusis and tinnitus, I wouldn't give a fuck about it.

I hope and also think that this treatment will provide benefit with tinnitus and hyperacusis. However I still think that this treatment will be a relief medicine similar to when you use inflammation creams and ice on a muscle strain to calm things for example before actually treating the underlying issue being the muscle. So SPI-1005 will provide some benefit when you take it, however when you treat the underlying issues like synapse damage it then theoretically will resolve an issue like tinnitus then properly.

 

[Born To Slay]

I hope and also think that this treatment will provide benefit with tinnitus and hyperacusis. However I still think that this treatment will be a relief medicine similar to when you use inflammation creams and ice on a muscle strain to calm things for example before actually treating the underlying issue being the muscle. So SPI-1005 will provide some benefit when you take it, however when you treat the underlying issues like synapse damage it then theoretically will resolve an issue like tinnitus then properly.

Yeah, I totally agree but having an effective pain killer and aid to help with hyperacusis pain in particular would be great and would make the time waiting for FX-322 and OTO-413 a lot more comfortable.

Just not needing to worry about setbacks anymore would be a dramatic life improvement.

 

[weab00]

I hope and also think that this treatment will provide benefit with tinnitus and hyperacusis. However I still think that this treatment will be a relief medicine similar to when you use inflammation creams and ice on a muscle strain to calm things for example before actually treating the underlying issue being the muscle. So SPI-1005 will provide some benefit when you take it, however when you treat the underlying issues like synapse damage it then theoretically will resolve an issue like tinnitus then properly.

Of course we will need to treat cochlear damage to fully resolve the issue, but if this can give us a good chunk of our lives back then it will be enough to cope until better regenerative treatments. Currently most moderate-severe noxacusis sufferers are housebound.

 

[Born To Slay]

Of course we will need to treat cochlear damage to fully resolve the issue, but if this can give us a good chunk of our lives back then it will be enough to cope until better regenerative treatments. Currently most moderate-severe noxacusis sufferers are housebound.

@FGG said earlier in the thread that the phase 2 COVID-19 trial ends in December, what a great Christmas gift it'd be if this drug is expedited and helps hyperacusis and tinnitus.

 

[weab00]

@FGG said earlier in the thread that the phase 2 COVID-19 trial ends in December, what a great Christmas gift it'd be if this drug is expedited and helps hyperacusis and tinnitus.

So there is a potential chance of getting this as soon as the end of 2020? That would be amazing.

 

[FGG]

So there is a potential chance of getting this as soon as the end of 2020? That would be amazing.

I would say if it works for COVID-19 there would still be a lag in using it off label because it would go to COVID-19 patients first but it wouldn't be as long as waiting until the trial ends for sure.

 

[Born To Slay]

So there is a potential chance of getting this as soon as the end of 2020? That would be amazing.

I'd say early 2021 because even after it's approved, there's stuff you have to do and we don't know how ready Sound Pharmaceuticals is to launch the drug but I'd say Q1 2021 would be very likely if it passes the trial considering the fact that anything remotely related to COVID-19 is a top priority.

 

[tommyd87]

@FGG said earlier in the thread that the phase 2 COVID-19 trial ends in December, what a great Christmas gift it'd be if this drug is expedited and helps hyperacusis and tinnitus.

I could be reading this incorrectly but I am wondering whether we will see this possibly available off label for the ear indication if the COVID-19 trial is successful. The COVID-19 indication will be much simpler and much quicker to get FDA approval for and I think Sound Pharmaceuticals can demonstrate fairly confidently that the medicine will work for ear stuff based off of their research and also the trials done so far.

 

[Born To Slay]

Hey @PeteJ if you haven't seen this thread yet, I'd take a look at it. This drug SPI-1005 could be here in a matter of months and it looks promising.

 

[Aaron91]

Let's assume for a minute that this drug is given the go-ahead in the coming months: how easy will it be for many of us to access it? I imagine governments would look to hog any meds that could be used to treat COVID-19 or its associated symptoms in case of a big outbreak. I also vaguely remember reading some time ago, back when there was a huge hype around hydroxychloroquine, that some governments around the world were halting pharmacies from selling it in the event it could help with COVID-19.

 

[Born To Slay]

I could be reading this incorrectly but I am wondering whether we will see this possibly available off label for the ear indication if the COVID-19 trial is successful. The COVID-19 indication will be much simpler and much quicker to get FDA approval for and I think Sound Pharmaceuticals can demonstrate fairly confidently that the medicine will work for ear stuff based off of their research and also the trials done so far.

I mean, at least in the US, off label prescriptions are written all the time. Just look at Gabapentin, it's only approved for partial seizures and postherpetic neuralgia and yet look at the all scripts it has for all these pain disorders and anxiety and stuff, hell, look at how many people got it prescribed to them for tinnitus or hyperacusis. It shouldn't be hard to get a script for Ebselen.

 

[Born To Slay]

Let's assume for a minute that this drug is given the go-ahead in the coming months: how easy will it be for many of us to access it? I imagine governments would look to hog any meds that could be used to treat COVID-19 or its associated symptoms in case of a big outbreak. I also vaguely remember reading some time ago, back when there was a huge hype around hydroxychloroquine, that some governments around the world were halting pharmacies from selling it in the event it could help with COVID-19.

Even if that happens at first, and that's a big if depending on where you live, COVID-19 is on its way to a vaccine so the pandemic can't go on forever. And when it's over, the government isn't going to stop the company from selling its drug.

But again, I don't think that's likely in wealthier nations like the United States.

 

[weab00]

Even if that happens at first, and that's a big if depending on where you live, COVID-19 is on its way to a vaccine so the pandemic can't go on forever. And when it's over, the government isn't going to stop the company from selling its drug.

But again, I don't think that's likely in wealthier nations like the United States.

Noxacusis sufferers are screwed once the pandemic ends and we have to go back to school and work in person.

 

[Born To Slay]

Noxacusis sufferers are screwed once the pandemic ends and we have to go back to school and work in person.

Well if it makes you feel better, that probably won't happen before next summer. We will likely have great news on FX-322 and OTO-314 by then. And this drug will likely be out.

So even as life crashes, we will likely be getting very good news regarding our condition.

 

[tommyd87]

Even if that happens at first, and that's a big if depending on where you live, COVID-19 is on its way to a vaccine so the pandemic can't go on forever. And when it's over, the government isn't going to stop the company from selling its drug.

But again, I don't think that's likely in wealthier nations like the United States.

I think this point is valid. Let's just say it takes a year to get a vaccine for COVID-19 and in that time SPI-1005 will provide treatment for this. Once a vaccine comes along, demand for SPI-1005 will probably reduce significantly. Therefore Sound Pharmaceuticals will want to continue selling this medicine for other indications. This will be allowed as once the FDA has granted approval for one indication it immediately enables the treatment to be prescribed off-label for the other indications.

Sound Pharmaceuticals knows that gaining approval for the COVID-19 indication is the easiest and fastest way to get the medicine through the FDA trials. It is probably also less expensive too since the FDA is assisting COVID-19 treatments. Therefore I believe that Sound Pharmaceuticals is utilising the COVID-19 indication as a way to gain approval quickly now so it can start getting prescribed for the treatment of things it was originally being made for like hearing loss. This is a win win situation for both Sound Pharmaceuticals and users of the medicine SPI-1005.

 

[Born To Slay]

I think this point is valid. Let's just say it takes a year to get a vaccine for COVID-19 and in that time SPI-1005 will provide treatment for this. Once a vaccine comes along, demand for SPI-1005 will probably reduce significantly. Therefore Sound Pharmaceuticals will want to continue selling this medicine for other indications. This will be allowed as once the FDA has granted approval for one indication it immediately enables the treatment to be prescribed off-label for the other indications.

Sound Pharmaceuticals knows that gaining approval for the COVID-19 indication is the easiest and fastest way to get the medicine through the FDA trials. It is probably also less expensive too since the FDA is assisting COVID-19 treatments. Therefore I believe that Sound Pharmaceuticals is utilising the COVID-19 indication as a way to gain approval quickly now so it can start getting prescribed for the treatment of things it was originally being made for like hearing loss. This is a win win situation for both Sound Pharmaceuticals and users of the medicine SPI-1005.

And there's no way it even takes a year to get a vaccine, every projection seems to think one will be available by next summer and that's a pessimistic estimate.

And I agree, it's pretty obvious they're going to do off label prescriptions. It'd be stupid not to. A drug like this for ears would likely become one of the most prescribed drugs in the United States. Other nations also but forgive me for being America centric, that's just how we are here lol

 

[FGG]

My only worry about potential SPI-1005's approval for COVID-19 treatment is that it's being tested as an adjunctive therapy for lung inflammation as well as anti viral properties.

I don't see that they are testing it *with* IV Dexamethasone, so it may have to be proven better than IV Dexamethasone for the former indication. IV Dexamethasone has great lung penetrance and seems pretty effective for COVID-19 related lung inflammation so it's a tough metric.

As far as anti viral properties, I'm not sure we can assess if the drug is good for this indication or not but fingers crossed. It shows some promise here as an adjunctive therapy.

If it's between potential improvement now or suicide, though (as some have indicated in other threads) and you want to try this drug, if you have a few grand, you can get this drug made. I have no idea how to assess the purity and reliability of labs that do this but Ebselen is available if you look.

Anyone wanting to go that route though, please do all of your own research first. It's always better to have all the info from full trial data first but I'm once again putting this out there because I know for some people it is literally life or death.

 

[weab00]

I'm trying to fully grasp in what ways SPI-1005 would be beneficial for noxacusis sufferers and how that would manifest into our everyday lives.

It will essentially eliminate inflammation so that means no more pain unless we re-aggravate it? And what are the implications of that in our day to day life? Does it mean we'd no longer be housebound assuming the drug is effective? And how often would you take it? Presumably right after a noise injury right.

 

[tommyd87]

And there's no way it even takes a year to get a vaccine, every projection seems to think one will be available by next summer and that's a pessimistic estimate.

And I agree, it's pretty obvious they're going to do off label prescriptions. It'd be stupid not to. A drug like this for ears would likely become one of the most prescribed drugs in the United States. Other nations also but forgive me for being America centric, that's just how we are here lol

I agree and actually also believe Sound Pharmaceuticals is just really savvy and playing the FDA process to their benefit.

I also see a high demand for this medicine in Australia too. There would be doctors definitely willing to prescribe it if it helped tinnitus. There would also be a high demand from patients for it too. Thus I definitely believe that this treatment would not only get released but also actually end up becoming a real winner if it is successful and all indications to date seem to suggest it will be.