Hough Ear Institute's Hair Cell Regeneration Project

[Markku]

To take a group of people with NIHL and give some of them the drug and some of them a sugar pill and then see what happens. Makes sense.

I would actually love to hear what @lcj thinks of this, as she's a biostatistician in the clinical trials space.

@lcj, can you ELI5, do you think the $50M-100M cost for Hough Ear Institute's phase 2 is par for the course? And what is your opinion on clinical trials generally? Could the system be more streamlined, saving money, time, and getting drugs faster for those in need? Is there any positive movement in the field that you'd like to note? And finally, what should a layperson do if they want quicker access to drugs in testing phases?

I did find the following:
"When we look at different therapeutic areas in Table 1, we see that the average cost of a Phase 2 clinical trial ranges from $7.0 million to $19.6 million, while the average costs of phase 3 clinical trials range from $11.5 million to $52.9 million."
(source)

So I guess the $50M-100M estimate for the phase 2 seems a bit high, but we can surely explore this subject in the interview. In any case it will be interesting to get Hough Ear Institute's viewpoints on clinical trials, how much leaner / affordable could they be made if there was a little less bureaucracy, etc...

We are looking forward to get the interview out ASAP!

 

[rei]

I don't know how anyone could read this entire thread and not want to bust some doors down.

 

[HootOwl]

Okay, my guess is the 50-100 million is most likely a typo from Justin when he mistakenly pulled the figure from his own quote on ROI here:

HEI won't make millions. The biotech firm that invests (50-110 million dollars) in our research and licenses it - they will make a lot of money.

Because 50-100 million is extraordinarily high for a trial in any phase going by the statistical data above. If that is correct I would be shocked.

Hopefully we can get some clarification soon.

 

[lcj]

I think that cost estimate is a very high for a phase II trial. You would only really see that with drugs that have a high payoff (for instance some of the more novel oncology compounds that can be $100,000+ per dose), otherwise you would never recoup those costs back and you basically won't have any investors and will run of out money before you ever get the drug to market.

Being that phase II's do not require multi-center, or a standard of care treatment arm comparison, and that the compound is one that is already manufactured (does not require a novel type of synthesis), I don't really see why the cost would be assessed so high.

The system could definitely be more streamlined. Part of the reason it takes so long is that the FDA has their own teams of programmers and statisticians and they basically take your raw data and repeat all your primary endpoint analysis for each study in your submission package to make sure that your results are correct. That having been said, the FDA approval process for NDAs (small molecules) and BLAs (biologics) is actually a little faster now than it used to be say 10 years ago. In addition, lots more drugs receive approval, and receive approval for fast track designation, or orphans status than they used to. In terms of access, I'm not very knowledgeable in that regard... I just think that more people should be eligible for access especially for diseases for which there is no cure or palliative treatment.

 

[Badger19]

If Hough's pill really is that promising, I find it odd that they can't find investors. There are loads of people with hearing loss. The first one to find a cure (or a significant improvement in hearing) can earn a lot of money.

 

[JohnAdams]

for instance some of the more novel oncology compounds that can be $100,000+ per dose

I did the math behind this drug and I calculated that it should cost around $10,000 give or take for a two day regimen which reflects the dosing schedule of their published scientific data and patents.

 

[Lucifer]

If Hough's pill really is that promising, I find it odd that they can't find investors. There are loads of people with hearing loss. The first one to find a cure (or a significant improvement in hearing) can earn a lot of money.

This drug passed Phase 1 trial in 2015 and I'm wondering the same thing why they couldn't find investors.

This drug could have well been in Phase 3 or in the market by now.

 

[spedgas]

If Hough's pill really is that promising, I find it odd that they can't find investors. There are loads of people with hearing loss. The first one to find a cure (or a significant improvement in hearing) can earn a lot of money.

What information do the noncommittal potential investors have that we do not? Something's keeping them away. I feel like we don't have the whole story here.

 

[JohnAdams]

If Hough's pill really is that promising, I find it odd that they can't find investors. There are loads of people with hearing loss. The first one to find a cure (or a significant improvement in hearing) can earn a lot of money.

It's because, this drug will not be profitable enough to be a reasonable payback for the outrageous cost of FDA trials.

Think about it. This cost is a barrier to entry that requires the kind of payback that can only be sustained by 10's to 100's of thousands of prescriptions being written every month. People in the target demographic for this drug are in the 100's per week nationwide. If it treats chronic tinnitus and hearing loss from trauma then there will be a huge flurry of demand initially from the chronic crowd and then 100's per week after that. This medicine is not attractive to investors.

 

[Lucifer]

It's because, this drug will not be profitable enough to be a reasonable payback for the outrageous cost of FDA trials.

Think about it. This cost is a barrier to entry that requires the kind of payback that can only be sustained by 10's to 100's of thousands of prescriptions being written every month. People in the target demographic for this drug are in the 100's per week nationwide. If it treats chronic tinnitus and hearing loss from trauma then there will be a huge flurry of demand initially from the chronic crowd and then 100's per week after that. This medicine is not attractive to investors.

You are right that demand will be less but @Justin De Moss did say it can be preventive as well so I think it will still be profitable.

People like us would not want tinnitus or hyperacusis to come back so if we know we are going to be expose to something loud e.g a concert then this can protect us and demand will still be high.

 

[Buzzy1]

@Lucifer
Hi I agree with you. The initial effects of the drug may not last for ever. I take high blood pressure tablets, it hasn't been cured by just taking one pill. The medication, if developed, might have to be taken for the rest of our lives.
Surely that will be profitable?

 

[JohnAdams]

@Lucifer
Hi I agree with you. The initial effects of the drug may not last for ever. I take high blood pressure tablets, it hasn't been cured by just taking one pill. The medication, if developed, might have to be taken for the rest of our lives.
Surely that will be profitable?

The effects are permanent. When taken immediately it prevents apoptosis of the hair cells, it also causes neuritogenesis. The neurites don't just die or retract when the pill is stopped. It is actually an amazing drug.

 

[Buzzy1]

@JohnAdams
Hope it's going to happen soon. 38 years of this and I'm not coping well at the moment. Tinnitus started with ear infection, never went, now its worse than ever. Hearing loss in both ears, it's awful. I'm 61 years old and would love for my t to get quieter. Hubby has it loud as well, but he's ok with at the moment.

 

[JohnAdams]

@JohnAdams
Hope it's going to happen soon. 38 years of this and I'm not coping well at the moment. Tinnitus started with ear infection, never went, now its worse than ever. Hearing loss in both ears, it's awful. I'm 61 years old and would love for my t to get quieter. Hubby has it loud as well, but he's ok with at the moment.

I'm sorry to hear that. This is truly an emergency that is not being properly addressed by anyone.

 

[JohnAdams]

The system could definitely be more streamlined.

 

[HootOwl]

Apologies as this might (probably is) a stupid question but is Otologic Pharmaceuticals considered an investor? Do they have access to the purse strings so to speak?

What's a tad strange is that the CEO of Otologic had every intention of moving to phase 2 immediately based on this news article from 2015 after phase 1 had been completed. So perhaps something unforeseen happened regarding funding for phase 2 back in 2016?

However I'm still hopeful that this will see the light of day! Even if it's not effective for chronic synaptopathy - as in 2 to 4 years out - it would be wonderful to have something to take immediately if you are inadvertently exposed to acoustic trauma to prevent the tinnitus or hearing loss from getting worse.

It still kind of hurts that this could be on the market right now, but it looks like things are starting to pick up if what Justin said back in October still holds true.

And we still have treatments for chronic synaptopathy in the pipelines of other companies so I'm not too worried.

 

[Badger19]

It's because, this drug will not be profitable enough to be a reasonable payback for the outrageous cost of FDA trials.

Think about it. This cost is a barrier to entry that requires the kind of payback that can only be sustained by 10's to 100's of thousands of prescriptions being written every month. People in the target demographic for this drug are in the 100's per week nationwide. If it treats chronic tinnitus and hearing loss from trauma then there will be a huge flurry of demand initially from the chronic crowd and then 100's per week after that. This medicine is not attractive to investors.

I'm not convinced. You could say the same for so many other drugs who do get adequate funding.

Why can Frequency easily get funding while Hough's pill is supposed to be better?

 

[JohnAdams]

I'm not convinced.

cool story bro. It is definitely not something you'd have to take everyday.

 

[just1morething]

@JohnAdams
Hope it's going to happen soon. 38 years of this and I'm not coping well at the moment. Tinnitus started with ear infection, never went, now its worse than ever. Hearing loss in both ears, it's awful. I'm 61 years old and would love for my t to get quieter. Hubby has it loud as well, but he's ok with at the moment.

Do hearing aids help at all? Noise definitely ruins your quality of life. It's hard to know when any IT ear injections or pills will be available. Sure are plenty of scam pills out there though. My noises change all the time, right now I hear a low pitched static sound. It is still annoying.

 

[FGG]

@Hazel, is it too late to add this question; "One of the published studies of HPN-07/NAC showed neural outgrowth when used in conjunction with BDNF. Is exogenous BDNF necessary to get this effect or would this be at physiologic levels?

 

[Harley]

If Hough's pill really is that promising, I find it odd that they can't find investors. There are loads of people with hearing loss. The first one to find a cure (or a significant improvement in hearing) can earn a lot of money.

The pill sounds promising indeed and my hat's off to its creators, but the lack of interest from investors boils down to one thing only.

Money.

I'm not trying to sound like conspiracy theorist, but these are my thoughts on what we might be up against:

The core of the problem is, that despite the popular belief, neither Big Pharma's or private investors main goal is to save us from this nightmare existence.
Their main goal is to make as much profit as possible, first and foremost.

I haven't read the whole thread, but it sounds to me that this pill could be the actual cure, instead of an ongoing treatment.
In which case, they realize that yes there is money to be made, but only for one time type of a sale.
Once the person is cured, that customer is gone.
For many of them, an outright cure might not be financially attractive.

Not to mention the fact that the hearing aid industry is a multi billion worldwide business and there could be all kinds of back room politics involved (as there usually is).
There are some very influential groups or individuals who stand to lose everything.
I'm pretty sure they will try to use every bit of their influence to make sure that this does not happen.

Now this is just my speculation only, but in order for this to make financial sense for investors, an outright cure treatment would have to have a very high price tag attached to it.
At which point, most insurance companies would not want to touch that one with a 10 foot pole, therefore most people would not be able to afford it.
This would translate into lower sales which would also hurt the bottom.line.

Now someone has mentioned that this pill could be also used for prevention, but considering most people have never even heard of tinnitus, it is hard to imagine anyone would spend that kind of money on something which they are not even aware of being in existence (and if they are, they likely think it's no big deal, thanks to the strong propagation of the pro-habituation myths).

So in a nutshell this is what the creators of this pill have to overcome.

Having said all that, I hope they do find a way to get this thing out there ASAP.

 

[JohnAdams]

The pill sounds promising indeed and my hat's off to its creators, but the lack of interest from investors boils down to one thing only.

Money.

I'm not trying to sound like conspiracy theorist, but these are my thoughts on what we might be up against:

The core of the problem is, that despite the popular belief, neither Big Pharma's or private investors main goal is to save us from this nightmare existence.
Their main goal is to make as much profit as possible, first and foremost.

I haven't read the whole thread, but it sounds to me that this pill could be the actual cure, instead of an ongoing treatment.
In which case, they realize that yes there is money to be made, but only for one time type of a sale.
Once the person is cured, that customer is gone.
For many of them, an outright cure might not be financially attractive.

Not to mention the fact that the hearing aid industry is a multi billion worldwide business and there could be all kinds of back room politics involved (as there usually is).
There are some very influential groups or individuals who stand to lose everything.
I'm pretty sure they will try to use every bit of their influence to make sure that this does not happen.

Now this is just my speculation only, but in order for this to make financial sense for investors, an outright cure treatment would have to have a very high price tag attached to it.
At which point, most insurance companies would not want to touch that one with a 10 foot pole, therefore most people would not be able to afford it.
This would translate into lower sales which would also hurt the bottom.line.

Now someone has mentioned that this pill could be also used for prevention, but considering most people have never even heard of tinnitus, it is hard to imagine anyone would spend that kind of money on something which they are not even aware of being in existence (and if they are, they likely think it's no big deal, thanks to the strong propagation of the pro-habituation myths).

So in a nutshell this is what the creators of this pill have to overcome.

Having said all that, I hope they do find a way to get this thing out there ASAP.

And the FDA trial costs are THE artificial barrier to entry that is stopping medication like this from entering the market.

 

[HootOwl]

So let's imagine the worst case scenario and this pill never makes it to market.

If it regenerated synapses/nerve fibers and subsequently reduced tinnitus in proof of concept models, then surely the other syanptopathy drugs that are entering phase 1 this year will act similar if not even a more potent manner. One company is already funded through phase 2, and the other shouldn't have any issues (that I can foresee but things happen).

I do really like the potentiating aspect of this pill (after reading through the information in the patent) but BDNF in isolation is still fairly effective. And NT3 can get you to practically native level of synapse repair by itself.

There's several irons in the fire for synaptopathy so I don't want people to feel like this pill is their one and only hope.

 

[HootOwl]

I'm not convinced. You could say the same for so many other drugs who do get adequate funding.

Why can Frequency easily get funding while Hough's pill is supposed to be better?

I'm curious where this "better" comes from because FX-322 and HPN-07 do very different things. One is a progenitor cell activator and the other is a potent antioxidant. They also target different damaged regions of the cochlea. FX-322 for mainly OHC hair cells. The pill for IHC synapses/nerve fibers.

Both are causes/contributing factors to hearing loss but to define which is a "better" drug for hearing loss ignores a lot of the nuance involved with cochlear damage, and by extension tinnitus.

As to the funding issue I still am unsure. The CEO of Otologic has every intention of moving to phase 2 for the pill back in their 2016 press release. I'm still confused how everything seemed to fall into the void, and I doubt we'll ever get an answer.

 

[JohnAdams]

I'm still confused how everything seemed to fall into the void

The love of money is the root of all evil.

 

[ChrisBoyMonkey]

View attachment 34430

The love of money is the root of all evil.

That's probably the smartest thing you've ever said. Money and power. Greed.

 

[JohnAdams]

That's probably the smartest thing you've ever said. Money and power. Greed.

I'm not the first to say it.

 

[Hazel]

Podcast recording with Hough Ear Institute now confirmed for 24 January!

Of course bear in mind we'll need 1-2 weeks after that still for editing, transcription, creating marketing collateral, etc.

Feel free to keep adding questions to this thread, we'll still include them if we can.

And try to keep the speculation in check until we've had a chance to hear directly from Hough Ear Institute and give them the opportunity to answer your questions first.

 

[Buzzy1]

I've had tinnitus for 38 years following an ear infection. Now I think my tinnitus has worsened due to hearing loss in both ears it's audible all the time, the only respite I get is sleep.

My question is "Will the Hough Ear Institute be able to help me?"

I would love to think that in the near future there may be a chance that I could hear "silence"

@JohnAdams

There is a Tinnitus Talk Podcast episode being done with the Hough Ear Institute soon. I think I'll wait and see what they have to say. With this condition I have to have hope, at the moment it's all I have.

 

[Bartoli]

@Hazel not sure if it has been asked already, but here goes my question: how does the antioxidant work in this pill?

In my understanding an antioxidant protects against damage from free radicals (oxidative stress).

What's the mechanism of action for chronic tinnitus?