Sound Pharmaceuticals (SPI-5557 & SPI-1005)

[Nick47]

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?

@Ela Stefan, all we know from that study is it reduced/reversed the damage from NIHL in rodents 3 months after trauma. That's interesting as that is towards the chronic end of things. That being said, rodents often do not translate to human findings. Still interesting at this stage!

 

[tomytl]

Are there any news of SPI-5557? It looks like it has not made any progress.

EDIT:

This is an interesting read retrospectively because the timetable was so optimistic.

It shows how theory and reality can differ from each other. I won't blame Sound Pharmaceuticals for that, I'm sure they are doing their best in this complex field.

Wayback Machine (archive.org)

 

[TeslaGuy]

Are there any news of SPI-5557? It looks like it has not made any progress.

EDIT:

This is an interesting read retrospectively because the timetable was so optimistic.

It shows how theory and reality can differ from each other. I won't blame Sound Pharmaceuticals for that, I'm sure they are doing their best in this complex field.

Wayback Machine (archive.org)

It seems not. I checked the website and SPI-5557 is still waiting for Phase 1. How long has it been like that? It seems the IND has not yet been filed. Well the science behind it looks promising by suppressing the p27Kip1 to promote regeneration in adult tissue. Hell, it is saying that it should regenerate hair cells, neurons and supporting cells. This indeed seems to be the most promising way to tackle hearing loss.

Is the function between SPI-5557 & SPI-1005 different? It seems that indeed the SPI-1005 is making good progress with the Phase 3.

I found this thread after accepting this recent failure we all read today about FX-322 and FX-345

 

[Hazel]

Check out our update video with Jonathan Kil, CEO of Sound Pharmaceuticals, in the ARO 2023 thread!

 

[Vadimus]

→ Sound Pharma completes enrollment in pivotal Phase 3 clinical trial of SPI-1005 for the treatment of Meniere's disease involving hearing loss, tinnitus, and dizziness

 

[NikoD]

Thanks for posting this. I've looked at the literature and it seems extremely interesting. It could possibly even help with slowing cochlear otosclerosis too.

 

[Philip83]

→ Sound Pharma completes enrollment in pivotal Phase 3 clinical trial of SPI-1005 for the treatment of Meniere's disease involving hearing loss, tinnitus, and dizziness

Demand for the STOPMD-3 trial was higher than anticipated and enrollment completed six months ahead of schedule with over 220 eligible patients randomized to either SPI-1005 treatment (400 mg twice daily for 28 days) or matching placebo treatment in 9 months.

I don't understand the "in 9 months"? There will be two trials where people first do 28 days of real drug or placebo, then the same 28 people do the trials again 9 months later but swap whether they get the placebo or not? Or do they mean that the trial will start in 9 months?

 

[Vadimus]

It could possibly even help with slowing cochlear otosclerosis too.

WOW! That would be just incredible! It's almost a superdrug then. Can you please share a link to the material where you saw that?

 

[GeraldHenders]

I don't understand the "in 9 months"? There will be two trials where people first do 28 days of real drug or placebo, then the same 28 people do the trials again 9 months later but swap whether they get the placebo or not? Or do they mean that the trial will start in 9 months?

From ClinicalTrials.gov:

Oral administration of SPI-1005 400 mg BID for 28 days, with 84-day followup.

Estimated Study Completion Date: August 2024.

 

[Nick47]

I understand SPI-1005 is only for Meniere's. Keep expectations checked!

 

[NikoD]

WOW! That would be just incredible! It's almost a superdrug then. Can you please share a link to the material where you saw that?

There's evidence Ebselen is a potent anti-osteoporosis agent. Cochlear otosclerosis is the demineralization of the cochlear bone and bony structures near the spiral ganglion cells, and hyper vascularization inside the cochlear (potential angiogenesis induced by the bone remodelling processes - Google: bone remodelling/osteoclast and angiogenesis to learn more). That is why Bisphosphonates are an upcoming potential therapeutic for cochlear otosclerosis.

Ebselen Is a Potential Anti-Osteoporosis Agent by Suppressing Receptor Activator of Nuclear Factor Kappa-B Ligand-Induced Osteoclast Differentiation In vitro and Lipopolysaccharide-Induced Inflammatory Bone Destruction In vivo

We still don't know why bone remodelling is so active inside cochlear of those with otosclerosis. It's a hard place to examine. There's one interesting study that showed stabilization of hearing for a small group of patients that were administered Bisphosphonates + long-term follow up.

I'm tempted to become a lab rat myself and administer Zoledronate to the round window at low concentrations in effort to preserve hearing. But it's a big risk and I don't have the necessary funds to commission something like this (I'd want to spend a year or so doing a few studies in animals).

Here is the study about Bisphosphonates and cochlear otosclerosis in a group of people. The drug was used off-label (thank god it's allowed in some countries):

Bisphosphonate therapy in otosclerosis: A scoping review

 

[in_LA]

→ Sound Pharma completes enrollment in pivotal Phase 3 clinical trial of SPI-1005 for the treatment of Meniere's disease involving hearing loss, tinnitus, and dizziness

Is this supposed to be taken in a pill form or as injections in the ear? I wonder if it has potential to help those with vestibular migraines or migraine-induced vertigo.

 

[F-u-T]

Is this supposed to be taken in a pill form or as injections in the ear? I wonder if it has potential to help those with vestibular migraines or migraine-induced vertigo.

SPI-1005 is taken orally as a pill.

 

[Vadimus]

There's evidence Ebselen is a potent anti-osteoporosis agent. Cochlear otosclerosis is the demineralization of the cochlear bone and bony structures near the spiral ganglion cells, and hyper vascularization inside the cochlear (potential angiogenesis induced by the bone remodelling processes - Google: bone remodelling/osteoclast and angiogenesis to learn more). That is why Bisphosphonates are an upcoming potential therapeutic for cochlear otosclerosis.

Ebselen Is a Potential Anti-Osteoporosis Agent by Suppressing Receptor Activator of Nuclear Factor Kappa-B Ligand-Induced Osteoclast Differentiation In vitro and Lipopolysaccharide-Induced Inflammatory Bone Destruction In vivo

We still don't know why bone remodelling is so active inside cochlear of those with otosclerosis. It's a hard place to examine. There's one interesting study that showed stabilization of hearing for a small group of patients that were administered Bisphosphonates + long-term follow up.

I'm tempted to become a lab rat myself and administer Zoledronate to the round window at low concentrations in effort to preserve hearing. But it's a big risk and I don't have the necessary funds to commission something like this (I'd want to spend a year or so doing a few studies in animals).

Here is the study about Bisphosphonates and cochlear otosclerosis in a group of people. The drug was used off-label (thank god it's allowed in some countries):

Bisphosphonate therapy in otosclerosis: A scoping review

Otosclerosis is in the exclusion criteria list:

SPI-1005 for the Treatment of Meniere's Disease (STOPMD-3)

Exclusion Criteria:

• History of otosclerosis or vestibular schwannoma.

 

[NikoD]

Otosclerosis is in the exclusion criteria list

It's in the exclusion list for very good reason, 1) so to not complicate the trials, 2) the drug will ultimately be licensed for a specific use, otosclerosis is not its intended use.

If the drug is approved and shows a way of reducing bone remodelling in the cochlea, it could be used off-label.

 

[Cernuto]

Even though I don't have Meniere's, I'm bumping this so SPI-1005 will get noticed by those of us who do have Meniere's disease involving tinnitus.

SPI-1005 looks to be the next drug on the horizon for us to try. I still have a tiny bit of hope left even after the recent, highly disappointing failures from Frequency Therapeutics, followed by Otonomy.

 

[Vadimus]

Not sure if this has already been posted here.

According to the Phase 1 study results, SPI-1005 is not more effective than placebo in the treatment of tinnitus (taking into account both TFI scores and tinnitus loudness):

SPI-1005 for the Treatment of Patients With Meniere's Disease

 

[DimLeb]

Not sure if this has already been posted here.

According to the Phase 1 study results, SPI-1005 is not more effective than placebo in the treatment of tinnitus (taking into account both TFI scores and tinnitus loudness):

SPI-1005 for the Treatment of Patients With Meniere's Disease

So, the drug is a failure? I'm surprised this isn't discussed more? I don't quite understand the results from that page, but maybe someone can explain it here.

 

[Vadimus]

So, the drug is a failure? I'm surprised this isn't discussed more? I don't quite understand the results from that page, but maybe someone can explain it here.

As I understand from these tables, the effect of SPI-1005 on tinnitus is the same as that of placebo:

 

[DimLeb]

As I understand from these tables, the effect of SPI-1005 on tinnitus is the same as that of placebo:

View attachment 55799

View attachment 55800

I'm trying to make sense out of the results, but I still can't lol. It seems more people got benefit in hearing loss and WiN tests than those who did not? Does the drug look beneficial in some people at least?

 

[AntonioM]

Based on 2 people that I have spoken to that are currently in the clinical trial, for one of them it has worked really well and it has helped lower the tinnitus. But it has also helped him with the vertigo and ear fullness that come with Ménière's disease. For the other person I spoke to, it hasn't done much for her. Although she said she had 1-2 weeks of almost no symptoms which she thought was a result of taking the medication after several weeks, but then her flare-up returned. So it seems that for some people the medication has done really well and for others not so much. In the Ménière's Facebook group, others who are in the clinical trial have posted mixed results. For some it's worked really well and for others not so much. Another encouraging result that seems to be reported by a few people for whom the drug worked is that their hearing feels like it improved.

 

[DeanD]

Based on 2 people that I have spoken to that are currently in the clinical trial, for one of them it has worked really well and it has helped lower the tinnitus. But it has also helped him with the vertigo and ear fullness that come with Ménière's disease. For the other person I spoke to, it hasn't done much for her. Although she said she had 1-2 weeks of almost no symptoms which she thought was a result of taking the medication after several weeks, but then her flare-up returned. So it seems that for some people the medication has done really well and for others not so much. In the Ménière's Facebook group, others who are in the clinical trial have posted mixed results. For some it's worked really well and for others not so much. Another encouraging result that seems to be reported by a few people for whom the drug worked is that their hearing feels like it improved.

For the two people you know, do they have mild, moderate or severe tinnitus? Do you know the cause of their tinnitus? Do you know if they had hyperacusis or sound reactive tinnitus alongside it?

 

[MFM]

In the Ménière's Facebook group, others who are in the clinical trial have posted mixed results. For some it's worked really well and for others not so much.

Are these people aware of whether they received a placebo or the real thing?

 

[Nick47]

Based on 2 people that I have spoken to that are currently in the clinical trial, for one of them it has worked really well and it has helped lower the tinnitus. But it has also helped him with the vertigo and ear fullness that come with Ménière's disease. For the other person I spoke to, it hasn't done much for her. Although she said she had 1-2 weeks of almost no symptoms which she thought was a result of taking the medication after several weeks, but then her flare-up returned. So it seems that for some people the medication has done really well and for others not so much. In the Ménière's Facebook group, others who are in the clinical trial have posted mixed results. For some it's worked really well and for others not so much. Another encouraging result that seems to be reported by a few people for whom the drug worked is that their hearing feels like it improved.

I'm convinced this is a DEAD DUCK.

1) All trial participants had Meniere's disease, distinguished by fluctuating low frequency hearing loss, vertigo and being episodic. They are not the normal chronic tinnitus patient.

2) This drug targets endolymphatic pressure, which brings on Meniere's disease.

Sorry to beat the negative drum, but unless you've been diagnosed with Meniere's, I think it's fool's gold!

If you want to grab something that 'might' be effective, a potassium channel modulator is your best bet.

 

[AntonioM]

I'm convinced this is a DEAD DUCK.

1) All trial participants had Meniere's disease, distinguished by fluctuating low frequency hearing loss, vertigo and being episodic. They are not the normal chronic tinnitus patient.

2) This drug targets endolymphatic pressure, which brings on Meniere's disease.

Sorry to beat the negative drum, but unless you've been diagnosed with Meniere's, I think it's fool's gold!

If you want to grab something that 'might' be effective, a potassium channel modulator is your best bet.

Yes... @Nick47, I agree it may not be the right solution for many people unfortunately. It doesn't seem to work for all Ménière's disease patients either based on what I observed, but I'm no expert for sure. I myself may try it if it does get approval because my situation is complicated and unclear as to whether or not I have Ménière's disease... My sister had Ménière's disease, same with my dad... and I for some odd reason for the first year, unlike my sister and my dad for whom the typical Ménière's disease symptoms came at them all at once, I had only been experiencing sudden and constant 24/7 loud tinnitus that sounds like a high-pitched electric sound or what I could best describe as an old TV set that emits an electrical sound. Along with that, early on, I also experienced sound sensitivity along with noise distortion or what I guess would be called dysacusis during the first year.

However, after a year of the above symptoms which I still have today, I then a few months ago started to experience ear fullness and random moments of dizziness that feel like I'm about to fall over but they have been very few and far in between. Hoping it doesn't escalate any further than this, however, I am starting to think that my case is leaning more towards Ménière's disease, especially with my family history. My doctor also said it can take some people several years to develop Ménière's disease.

My sister said she recovered and has been in remission for 10 years now after dealing with extreme symptoms for 2-3 years. She says her tinnitus doesn't bother as much anymore. Occasionally it will get loud but subsides. Mine hasn't subsided at all and I'm a little over a year into this mess. So I'm thinking maybe I could try this medication along with potassium channel openers together and see what happens, unless I get lucky like my sister and naturally improve by this time next year, which will have marked my 2 year anniversary with this horrific condition. My dad has bad vertigo for a full year but his hearing deteriorated. He also had a sudden episode of vertigo when his Ménière's disease started. But today he said he's fully recovered. So I'm crossing my fingers that maybe I'll have the same outcome and have a "burn-out" as some doctors say can happen with Ménière's disease patients after 2 years.

Here are some random quotes for anyone interested from the clinical trial participants who have shared their experiences with SPI-1005 on the Ménière's's Facebook group. Some are really bad, some very promising and other comments don't seem to indicate any big change for trial participants. Keep in mind these are just a small handful of people who are sharing their experiences. There may be many more participants who are not active on social media, so hard to really assess progress of this trial, but here goes:

Been on real drug 6 weeks only change is worsening tinnitus I'm riding it out

I've been on the real drug for 7 weeks. Just recently noticed that my pulsatile tinnitus is gone in the very early morning hours. Unfortunately, it returns during the day. Not giving up yet!

Keeping it short! currently on month 3 bottle for two weeks know and I feel like myself again. Yes it works and I hope it works for you too, I can almost say i feel normal. The following are my symptoms and how I'm currently doing.

1: My absolute worse symptom TINNITUS: low tinnitus where I'm able to ignore it.
2: Dizziness: I haven't had a severe case of dizziness since I started the open label.
3: Ear fullness: I still get ear fullness for couple minutes maybe twice a week.
4: Face pain: gone.
5: Brain fog: gone.

Finished week 10 of SPI-1005 drug. Still enjoying lower tinnitus, but fluctuates a little. Hearing getting better in worst ear, woo-hoo! I'm experiencing some dizziness, I think because my hearing/balance is adjusting, so that's good news. Nothing vertigo-like however. More sleepy than dizzy. I just take it easy those days. I came home from Walmart the other day, and I noticed no roar from having been there, nor from the rattling plastic bags. Let's hear from others in the study, please!

22 weeks on SPI-1005 and still no vertigo! Not much tinnitus or hearing improvement yet. I did, however, just come back from a week away from home. I was not able to tolerate sound in 2 churches, but I made it to my 40th high school class reunion.

I'm looking for anyone out there who is on the clinical trial for SPI-1005. It has been 3 months for me and I haven't seen any improvement. I've had 3 episodes and tinnitus is as loud as it's ever been. I guess I'm trying to find out if it has taken longer than 3 months to notice any improvement. Any responses are appreciated. And yes I'm on open label extension.

I am now at 4 months on SPI-1005. Open label. No improvement and my tinnitus seems to be progressively worse. Now seem to be losing hearing in my good ear. Anyone else experience the same thing. I'm considering stopping as it has cost a lot of $ flying up to the clinic to be getting zero results. Beyond frustrated.

So I've been on Ebselen/SPI-1005 for three weeks now. For the first time in at least three years I was able to experience walking in a straight line in the dark without holding on to anything! I didn't know it was even possible anymore. I'm even riding in a car right now, been on my phone for a while and I'm not sick!

I am more and more optimistic about this drug and what it can do for so many of us! I still fear an attack but am hopeful I'll be able to live life without that fear again in the near future.

Just sitting here watching Wimbledon and my tinnitus went from it's constant manageable sound to jet roaring in about 15 seconds. Hope it goes back to what it was! And I'm in the SPI-1005 trials on the real drug.

I'm in the OLE now. (Real drug) started 1 March so through 11 days. First 9 days were not great had 1 day of clear hearing, 8 were some of the lousiest ear fullness, tinnitus and distorted hearing days in recent memory. But on the 10th day, much much better. Two days, and counting of very good improvement. Hoping it's sustainable and don't cycle back. I'd say it takes some time to work. If it gives us some small amount of control, this will be huge for us.

 

[DimLeb]

I'm convinced this is a DEAD DUCK.

1) All trial participants had Meniere's disease, distinguished by fluctuating low frequency hearing loss, vertigo and being episodic. They are not the normal chronic tinnitus patient.

2) This drug targets endolymphatic pressure, which brings on Meniere's disease.

Sorry to beat the negative drum, but unless you've been diagnosed with Meniere's, I think it's fool's gold!

If you want to grab something that 'might' be effective, a potassium channel modulator is your best bet.

I totally agree with your points. One must also consider that their improvement could be from natural remission of Ménière''s disease. But as I understand, from what I have read and my own experience/symptoms, in some cases the cause of tinnitus might as well be hydrops, especially if you are in the "unknown cause" category (including me).

I'm convinced that there are way more atypical forms of hydrops than the standard Ménière's disease, and if Ménière's takes years to diagnose, then that takes a lot more, if ever. Acoustic traumas can also cause hydrops as a result, as I read somewhere.

It's very hopeful to have a drug like this developed, because it can potentially help a lot more people than just Ménière's disease sufferers. Just like how doctors here in Europe prescribe Betahistine for anything involving ear pressure/sudden hearing loss/tinnitus etc.

 

[EkkoMusic]

Acoustic traumas can also cause hydrops as a result, as I read somewhere.

Agreed, but from my understanding, that is a direct result of the trauma itself, and it doesn't create chronic/fluctuating hydrops, correct?

Here are some random quotes for anyone interested from the clinical trial participants who have shared their experiences with SPI-1005 on the Ménière's's Facebook group

Very interesting to see -- from my perusal, it looks almost like a 50/50 split of Meniere's patients seeing improvement versus people seeing no improvement or worsening. Between this and the SPI-1005 thread on Menieres.org, I almost feel like we have enough anecdotal reports now to know the results here are going to be very mixed. My question is (which I imagine is easy to answer), what percentage of benefiting patients are needed for the trial to be a success and the drug to make it to market? If it's, say, a solid 50/50, is that enough?

It's ever curious to me why some respond, and some don't. It makes me think about how we should equally spend time focusing on the etiologies of Meniere's disease and its root causes. Maybe the drug works wonders if your symptoms are more of an autoimmune origin but less so for something more vascular, trauma-related, etc.

 

[xela1225]

More news about SPI-1005:

→ Sound Pharmaceuticals' IND Involving Cochlear Implantation Allowed by the FDA

 

[Nick47]

More news about SPI-1005:

Worthy find. SPI-1005 will do nothing for tinnitus unless caused by Meniere's disease. It is going down the SENS-401 route as an otoprotective drug.

 

[BlueMoon86]

Worthy find. SPI-1005 will do nothing for tinnitus unless caused by Meniere's disease. It is going down the SENS-401 route as an otoprotective drug.

Do you think tinnitus caused by Meniere's disease differs from other tinnitus? One ENT said off-hand that he thought I had endolymphatic hydrops, which is apparently the same thing. I've kinda had high hopes for SPI-1005 but I don't have much use for something "otoprotective" when my hearing is already buggered.