Sound Pharmaceuticals (SPI-5557 & SPI-1005)

SPI-1005 is currently going through the phase 3 trial for one of its multiple uses (it is apparently suitable for respiratory issues like cystic fibrosis along with ear issues).

Furthermore Sound Pharmaceuticals have discovered that SPI-1005 is looking like it's useful to help with the respiratory stuff related to COVID-19. Therefore this will surely fast track this medicine considering the seemingly high priority COVID-19 has when it comes to treatments/medicines.

Therefore if this treatment either passes its current phase 3 trial for whatever it is being trialled in or it passes its current phase 2 trial for COVID-19 and attains FDA compassionate use allowance (which is very obviously all but guaranteed to be granted), I can see it being released in the near future.

Obviously we will be able to obtain it for off-label treatments.

 

How have results been for hearing loss/tinnitus?

 

No idea I will try to find out some meaningful details.

 

Sound Pharmaceuticals just published this less than a week ago concerning their drug and aminoglycosides:

A Novel Mouse Model of Aminoglycoside-Induced Hyperacusis and Tinnitus

 

Insightful share. I am really looking forward to this drug becoming accessible.

 

This looks really, really promising.

This drug looks like it will have very good benefit but it has also seemingly gone under the radar. Right now I am thinking this will do a lot of good in conjunction with the other treatments.

 

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.

 

This is where I'm hoping that 'noxacusis setbacks = instant inflammation' and it can be taken as soon as you know one is on the way. I can only speak for myself but I know the distinct feeling when a noise has done enough to trigger an anticipated setback. I know regeneration would be the best but to be able to negate the symptoms of a setback would be so good for now.

 

There are only two methods which could overcome the problems with correct diagnosis.

The first is to trial treat so we take the medicine and see what happens.

The second is that Sound Pharmaceuticals runs some kind of clinical trials to see what the benefits of the treatment are based off of people’s individual issues.

I agree that this would be a good stop gap to take if you knew it was going to deal with inflammation issues immediately when you had them.

I tend to agree with you that regeneration would be the best outcome as it would deal with the underlying problems.

 

Right. Patients are left with the "trial treat" option which is fine when drugs are safe but it might be financially unaffordable to some, especially if travel is involved on top of the medical expenses.

 

I don’t disagree with this, although the reality seems to be one of these two options. If the cost of this treatment is inexpensive, it is fine, but if it is expensive, then obviously I agree with you it is not.

Now this is why I am suggesting that it would be better if Sound Pharmaceuticals chose the second option and actually attempted to test people’s benefit from the medication. This way Sound Pharmaceuticals could provide some direction and clarity on this treatment's suitability for people.

 

I read this earlier. Am I reading this wrong that this drug is currently available anyway for certain conditions? (Bipolar and hearing loss). Would that not mean that it's deemed safe for possible off label use?

Treating COVID-19: Bipolar drug shows promise and other hopeful findings

 

I don’t think that this medicine is available yet. I know that they had got positive results in the Meniere's phase 2 trials and I think that they jumped onto the COVID-19 stuff once they knew that it could be beneficial.

I think that they would try and get this treatment out ASAP using whatever indication works best to get it to pass the FDA requirements so they could then prescribe it off label.

 

It's not currently available and hasn't been approved for anything (yet) but it is being tested for a number of indications including bipolar disorder.

 

Let’s say it gets approved for treating respiratory issues related to COVID-19. Do you think we would be able to easily access it off-label for cochlear inflammation?

I can see a hearing loss drug being used off-label for tinnitus, but I don’t see many physicians easily prescribing a Ménière’s-related drug for tinnitus (especially when it will have been approved only for COVID-19 related symptoms). I feel like we would have to really convince them by showing them the benefits from previous trials.

 

I think that it would depend on the benefits shown for other indications. If it has passed phase 2 trials for Meniere's for example, I can see some doctors thinking that this is sufficient enough evidence and reason to be willing to prescribe it for tinnitus.

 

COVID-19 is common enough, we would at least get more and more reports of tinnitus improvement to justify off label use to doctors with.

 

If need be, I would prepare a 20-page research paper for my physician on the potential benefits of this drug. At this point, I will not take no for an answer.

 

@tommyd87 does it need to be prescribed by an ENT or can, say, a GP do it?

 

Am I understanding correctly that they are only on mouse model stages for the anti-inflammatory treatment?

 

They are in phase 3 for Meniere's.

 

They are in phase 3 for Ménière’s, but it could very well treat cochlear inflammation for some of us here.

The research article was just highlighting the relationship between Aminoglycosides and hearing damage.

 

Their website states that they are currently in phase 2 trials for noise induced hearing loss.

Companies often complete research work for various side studies which test the medicine benefit while conducting clinical trials. Frequency Therapeutics is doing this with groups such as tinnitus sufferers. Furthermore, this might also just be a case of delay between completing the research work in the lab and producing the journal paper.

I don't think that this research will have any major bearing on the progression of the clinical trial. In fact I'd predict now that this has been completed, it will actually mean they can speed up the trials on people because they have obtained the meaningful information they need.

 

No idea yet. I actually am unaware where you are located and so cannot comment specifically about who could prescribe medicines.

In Australia, an ENT (not a GP) would need to prescribe this since it is a specific ear treatment for something that is probably more specific than what a GP would deal with. Thus it is actually quite likely that this would be restricted so only specialists dealing with the specific conditions this targets would be allowed to prescribe it. This usually happens with most specialist treatments like SPI-1005 that are not your everyday type of medicines like cortisone creams for contact dermatitis.

 

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.

 

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.

 

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

 

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.

 

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).

 

Inflammation is one potential cause. Anything that impairs normal auditory signal can cause tinnitus.

You may not have meant to imply (maybe it's just how I read that though) that inflammation is the sole cause for everyone but in case it is ambiguous, I don't want people to fall into the trap of thinking there will be one cure for all as treating the underlying cause depends on treating the underlying cause for each individual.

That's why Frequency Therapeutics is testing their drug for tinnitus, because in people with hair cell loss, that's the reason for the abnormal auditory signal.

Anyway, re: Ebselen. It's actually a really complex drug the more I read about it, deceptively so. It's definitely not a lot like NAC other than antioxidant properties. It inhibits certain target enzymes (through reversible redox reactions), is a voltage gated calcium channel blocker, too. I wrote this in another thread about that:

"It appears that Ebselen also has voltage dependent calcium channel blocking activity. This explains why it might be especially useful as another "bomb blast pill", which they are recruiting for now.

Apparently, with acute ototoxic or noise exposure the neuro excitability contributes to an influx of calcium ions into the OHC that is large enough to overwhelm the buffering. This can damage the mitochondria and, ultimately, the cell. So, the theory goes, if you can block the influx and attenuate it, you can prevent permanent damage.

This goes into more detail about calcium's role in acute hearing damage:

Tonotopy in calcium homeostasis and vulnerability of cochlear hair cells

Anyway, this does make me wonder about side effects in certain people. For example, Amlodipine blocks similar channels and lowers blood pressure. So if someone already had hypotension or were already on that drug (not sure how much cross reactivity there is) maybe there could be excessive hypotension, for instance or a bradycardia (which is uncommon with Amlodipine and reversible when stopped). The blood pressure / vasodilation effects also might help blood flow in the ear (which is is an additional reason it might help Meniere's)."

All that to say, it passed two phases of clinical trials so far without safety issues so that's certainly encouraging.