Hough Ear Institute's Hair Cell Regeneration Project

From memory, Oblato only own the rights outside of the US. Also when I see the words partner with, it seems to indicate that there may also be some part of the agreement where Hough has to fund and meet certain requirements in order to maintain their share and profit.

If I am not mistaken from what I was reading the term proof of concept study seems to refer to a phase 2a trial. Therefore once they have seen it works or this has been delivered they will proceed to running the more in-depth 2b and 3 phase trial.

 

https://houghear.org/wp-content/upl...air-cell-regeneration-Review-and-new-data.pdf

 

"We also show for the first time that the cochlear epithelium of the neonate retains regenerative competence even in the state of a flat epithelium."

Neonatal mice (unlike neonatal humans or adult mice and humans) retain a regenerative capacity closer to birds (but not as robust). Now do this in adult mice and I'll be jumping for joy!

That chart was pretty interesting, too. It does show that canalostomy is superior to cochleostomy for viral vectured therapies. I think Novartis would have had way better trial results (and maybe even had a product on the market already) if they didn't use such a destructive surgical technique for their therapy.

 

i have no clue regarding Novartis. Now what did they do and offer? Thank you.

 

They had an Adenovirus vectored gene therapy in trials for hair cell regeneration but was put on hold twice for safety issues no doubt because they used cochleostomy to administer it since it was viral vectored.

There is a thread on CGF-166 in the Research News section.

 

For someone who doesn't understand the science behind this, can you explain this to me, thanks?

 

Basically, the surgical approach needed for a viral vectored therapy (you can't use round window delivery through intratympanic injection with these very well) is very destructive (cochleostomy) and may produce enough damage and inflammation where you don't get good results. There is a newer, safer surgical approach called canalostomy but Novartis didn't use this approach (probably because it's newer and their trial started a few years ago).

 

Right. What you're saying is that they should seriously evaluate whether to commence trials again with the new method? Maybe this then might provide further benefit and results?

 

I personally think they also need to reevaluate their patient population. Some of their patients had profound loss and you need a different method to transduce flat epithelia. I think they are probably weighing their options but I think they could be more successful with different parameters and canalostomy instead. Just my opinion.

 

It might also be that expressing ATOH1 is not enough to yield a significant amount of hair cells.

 

Maybe, but a few patients did see noticeable clinical improvement (though the exact improvements were not published) and these patients had less severe loss. Because of the invasiveness of the procedure, only very severe to profound patients were included in the trial. Though that may change now (along with the method of delivery).

If ATOH1 was shown to be a completely ineffective method, I'm sure the trial would be cancelled instead of suspended twice as Novartis has done. It would seem like a colossal waste of money otherwise for them to keep funding it and they are a very experienced pharmaceutical company.

 

@Jurger, the full article is behind a paywall but this is from 2015:

https://www.tandfonline.com/doi/abs/10.1517/14712598.2015.1009889

"While the feasibility of Atoh1 gene therapy in the cochlea is largely dependent on the severity of the hearing loss, hearing restoration can be achieved in some situations."

I still think Frequency's method is better as it is not a transduction method and also doesn't deplete support cells but I think there might be some cases where this could be useful. Particularly with canalostomy.

https://www.tandfonline.com/doi/full/10.1080/00016489.2019.1654130?src=recsys

 

Do you mean profound hearing loss across the spectrum or just in certain areas?

So now Novartis would need to restart the trial again from scratch with canalostomy in order to try and see if this worked with whatever medicine they are using in this trial?

It is somewhat interesting that they didn't release the data from the first trial and also that they only suspended it and did not cancel it. It is a wonder whether they think that they will retry this again and possibly with this new procedure? It obviously indicates that they have something that they want to work with and for a major company I cannot see them continuing with the process and continuing to invest if they think that they cannot get any meaningful benefit in doing so.

This treatment trial in rats is quite old, although actually had some very positive success, as did the second one when it supported the initial contention of the first one and also showed it is suitable to use it for treatment:

• Canalostomy as a surgical approach for cochlear gene therapy in the rat
• Canalostomy As a Surgical Approach to Local Drug Delivery into the Inner Ears of Adult and Neonatal Mice

It makes me actually wonder whether Novartis might try this technique and why they have not discontinued their study altogether. Maybe they think now that they have turned positive outcomes in the first trial through the other method they might make even better in roads with this one.

 

I meant the opposite: that heir drug might be more useful in the very severe category vs profound. ATOH1 seems inadequate for transducing a more end stage cochlea.

The advantage of the surgical approach would be penetrance anywhere in the cochlea. Especially with canalostomy, both perilymph and endolymph could be accessed so apex and base could be reached.

Novartis hasn't said they plan to change their surgical approach but it would make sense to imo since cochleostomy produces so much inflammation as well as use different selection parameters. Just my speculation. I suppose the other option would be to try dosing it with a heavy anti inflammatory protocol.

This probably doesn't belong in this thread though since there is a Novartis thread.

 

New video up on the Hough Ear Institute YouTube channel about the FDA approval process.

Hough Ear Institute - FDA Approval Process

 

Man, I’ve been critical of this method and speed, but that was some good, clear info on the process. I just wish I could hack YouTube and have that video play over every other to raise awareness.

 

When do you guus speculate "the pill" will be available for the general public?

 

I hadn't realised they've also come up with an inner ear injection. Interesting stuff...

 

Great video @Justin De Moss.

 

The timeline they have given is two to four years. They have told us they need to do the proof of concept research study first, and then the phase two trial.

They have also been given the Fast Track status from FDA so they can release the drug once phase two is done provided they can show it has benefit as this is the only criteria not yet satisfied.

The only query many on Tinnitus Talk have is why do they need to do a proof of concept study before phase two and why do they need donations from individuals to do that.

Once these two things get answered it will alleviate many people's concerns here.

I also don't get why they wouldn't push it forward faster from the point of view that they can financially benefit sooner from a great product if they put it out on the sales market.

 

Thanks mate for putting your invaluable time in answering me in such a well articulated way.

Every time a potential treatment or cure has been on the horizon, lots of tricky questions have arosen. This forum is prone to deep speculations which is good for some perspective. Thanks again and hugs.

 

I think the truth is that the skepticism, questioning, debating, arguing and speculating seriously significantly enhances the discussion.

There is an absolute need to challenge things though. If you don't, then the information around an issue is not as helpful or good as it might be.

We should be querying Hough Ear Institute on the reason why do they need to do a proof of concept study first before being able to do the phase two trial.

We are ultimately the ones taking the treatment and funding their product.

I'm pretty positive that we know their product works wonderfully and will get granted early release. We simply just don't have any insight into why they need to do that proof of concept study first.

 

Was it ever reported anywhere that they received Fast Track status? And assuming they really did, is that a guarantee to skip phase 3?

 

Fast Track is not a guarantee to skip phase 3 at all. Regardless, I likewise do not remember hearing Hough got Fast Track status for their pill and I would like a link.

 

I was able to find a comment from Justin De Moss from April 20th in this Hough thread claiming they got Fast Track status.

 

Yeah you found it. Thanks. This makes sense why we might see this sooner rather than later. This also again makes me feel far more confident in the benefit through this treatment.

 

Any idea when they are going to start Phase 2 clinical trials? I doubt they will start this year.

 

I love that tinnitus is specifically mentioned in this video.

 

What is the Hough pill's mechanism of action?

 

Can be found here:

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0183089

Per Justin, the fact that it could also re-form synapses was found by surprise/happy accident.