Denver Man Gets Gene Therapy to Restore Hearing

[Aaron123]

This should probably be in the Genvec thread. I searched recently and as far as I can find there is no new news.

 

[jeff W]

http://www.dddmag.com/articles/2016/03/market-potential-gene-based-medicine-how-big

 

[Reinier]

Are predictions like these realistic?
I hope predictions are conservative and we "are in for an unprecedented wave of new initiatives" (-;

And now for something completely different:
I have noticed earlier that receiving a notification in my email account regarding new posts are not always received.

 

[tomytl]

Hi,
What will happen with Genvec highly depend on what Novartis is doing with the trial using Atoh1.
I'm very happy they started this trial at least, it's something I was waiting nearly 10 years.
I personally expected a lot, but in the field of other researchers chances has been hold very low that
they will have good success to restore hearing and the trial itself is also very cautious, so it's about
5 to 10 decibel.
Anyway, If there would be proof (and it's a trial for proof of concept and not really a therapy for
the masses) that would show that there is a regenerative potential.
From what I understand, many other strategies in hair cell regenertion has something to do with Atoh1,
so the gene itself is very important.
Don't forget, it's very brave of all participants to join this trial and I understand that all people involved should
be very careful. If there is something going out of control gene therapy might get some backdraft again.
Would be nice, if they can find something useful out of this trial even if it's just a save delivery method.

It's awesome what's going on, nearly everyday we can read some news... ofcourse, all in it's first steps.
But remember the finding of the effect of the LY-Alzheimer Drug, it's possible that the drug is already existent and used for something different...

People who are in the 20 ies with hearing problems might have a very good outlook for a drug which can help them. For me in the beginning of the 40 ies it might be more critical to experience. But maybe something to protect or avoid age related hearing loss would be nice...

 

[Reinier]

Anyway, If there would be proof (and it's a trial for proof of concept and not really a therapy for
the masses) that would show that there is a regenerative potential.

This I think is most important. If regeneration takes place and lasts it would be such a milestone. If it is 5 or 10 dB is not very important initially. If the principle works, as it does on other mammals, scientists can find out why only 5 or 10 dB. This is why I am so amazed it remains so quite regarding the people that took part in the trials and told they could hear new sounds. I cannot understand this. If it where me, I would let everyone know. So I Imagen these people are asked to keep quiet. What also is possible is that this improvement was only for a short time

Don't forget, it's very brave of all participants to join this trial and I understand that all people involved should
be very careful. If there is something going out of control gene therapy might get some backdraft again.

Don't forget that on so many animals these drugs are tested. It is not 100% certain that it will work for humans too, but if it works for other mammals, what are the chances it will not work for humans? I wonder if statistics are available on the internet regarding this.

 

[Silvio Sabo]

Don't forget that on so many animals these drugs are tested. It is not 100% certain that it will work for humans too, but if it works for other mammals, what are the chances it will not work for humans? I wonder if statistics are available on the internet regarding this.

The statistics are irrelevant in this case. It's all about how different the tested animal is compared to the human in what you are testing. It's irrelevant how many prior trials for different things have held up. It doesn't say anything about how successful THIS trial is going to be.

It can also be very small differences that make huge impacts.

 

[tomytl]

Considering the trial, there is an update on clinicaltrial.gov from the 7th of March and still recruiting.
And in an quarterly Genvec notice they write, that they have no information about sone adverse reactions from the 9 participants, which is also a good sign...
So maybe it's going to continue....

 

[Reinier]

It doesn't say anything about how successful THIS trial is going to be.

This I do not understand. Why all the testing on animals if the outcome is irrelevant?
A lot of it is about how cells can be manipulated. It must be relevant if we want to justify all the animal testing.

 

[Aaron123]

there is an update on clinicaltrial.gov from the 7th of March and still recruiting

It's obviously good that they did not change the recruiting status. However, I'm not sure I would read too much into the changes on clinicaltrials. The history of changes shows minor wording changes (why in the world go in yesterday and remove the word "current" twice?), but they did not change it to "paused" and back to "recruiting": https://clinicaltrials.gov/archive/NCT02132130

So maybe it's going to continue....

I hope you are right. This quote from the quarterly report is particularly interesting (I added the bold):

In early January after a total of nine patients had been treated, we were notified by our partner Novartis that enrollment had been paused based on a review of data by the trial's Data Safety Monitoring Board in accordance with prespecified criteria in the protocol," said Douglas J. Swirsky, president and CEO of GenVec. "It is important to note that we are not aware of any significant adverse events in the trial, and while there is no certainty, we believe that enrollment in the dose escalation portion will resume in the coming months.

Here is a link to a pdf of a presentation by Novartis to the NIH Recombinant DNA Advisory Committee (RAC). http://osp.od.nih.gov/sites/default/files/1_1260_CGF166_Klickstein.pdf that gives the trial protocol including the trial design (page 19) and the prespecified criteria for stopping (page 25). (Note: this presumably isn't the entire protocol so there could be other reasons to stop, pause, etc that aren't included here. I haven't been able to find something that looks like a complete protocol.)

Given that 9 patients were treated, it looks like they made it through 2 rounds of Part B (page 19) so there should be a "Full Safety Data Review" which may be the point at which they paused it.

It seems hard to believe that the DSMB stopped the trial for something other than a safety issue. Also interesting and (I think) new that Genvec believes the trial will resume "in the coming months" - not weeks but months. If there are no AEs, why a months-long "pause" that wasn't in the plan? Also not sure what to make of the statement that they (presumably Genvec?) are "not aware of any significant adverse events". Perhaps I am too cynical, but that seems different than saying that "there are no adverse events".

Just some things to think about while we wait.

 

[Silvio Sabo]

This I do not understand. Why all the testing on animals if the outcome is irrelevant?
A lot of it is about how cells can be manipulated. It must be relevant if we want to justify all the animal testing.

I didn't say the outcome of the test on animals is irrelevant. I said that statistics from prior trials for other drugs are irrelevant. I understood your question as: What are the statistics of human trials being successful after animal trials? And the answer is: there is no way to tell whether THIS trial will be successful or not from those kind of statistics.

The reason we have to try it on animals first is because frankly we can't do it on people unless we at least assume it works and is safe. There would be an outrage if someone died because a drug wasn't tested on animals first.

 

[lymebite]

GenVec stock is up 45 percent today. Must have been good news in the earnings report. Did anyone listen to the webcast?

http://www.prnewswire.com/news-rele...r-end-financial-results-300232899.html?$G1Ref

 

[Ricardo1991]

Woah woah woah woah guys, let's calm down. I'm sure that there will be more information available soon. I know it's crappy what we're feeling right now but this man also deserves his privacy.

 

[jdjd09]

GenVec stock is up 45 percent today. Must have been good news in the earnings report. Did anyone listen to the webcast?

http://www.prnewswire.com/news-rele...r-end-financial-results-300232899.html?$G1Ref

So, seriously, does anyone know what the results were? I need some hope if any that maybe I can have my hearing restored somewhat in 5-10 years. I really lose hope with life. If I can get 10-20db increase in my hearing, that would be fine. More would be even better.

 

[lymebite]

Here is an excerpt from the transcript of the March 9, 2016 GenVec conference call and a link to the entire text:

http://www.msn.com/en-us/money/othe...5-results-earnings-call-transcript/ar-AAgBefF

Let's get started by discussing the status of our collaboration with Novartis to develop novel treatments for hearing loss and balance disorders. As we announced previously, we were notified by Novartis in early January that patient enrollment in the Phase I/II study of CGF166 in patients with severe to profound hearing loss had been paused. This pause was based on a review of data by the trial's data safety monitoring board in accordance with pre-specified criteria in the trial protocol. While we are disappointed with this development, as with any first in man study, we recognize it is important to proceed with care to gain a broad understanding of the therapeutic profile of the product and its delivery.

Novartis will continue to collect safety and efficacy data on the nine patients who have been treated in this study before determining whether to proceed with incremental patients. It is important to note that we are not aware of any significant adverse events in the trial, and while there is no certainty, we believe that enrollment in the dose escalation portion of the trial will resume in the coming months. As a result, we believe that the trial could be completed sometime in 2017, as previously expected. Although we cannot share specific details, we believe that the safety signal observed in the trial relating to the pause in enrolment will be determined to be not clinically meaningful. GenVec is awaiting further guidance from Novartis on the CGF166 study, and we are committed to updating shareholders when we gain greater clarity. Again, we believe the trial has a high probability of resuming patient enrolment in the coming months.

 

[jeff W]

Stock price spiked, expect announcement of the resumption of trial in coming weeks.

 

[Reinier]

GenVec stock is going up again (-;

 

[Nick Pyzik]

So, seriously, does anyone know what the results were? I need some hope if any that maybe I can have my hearing restored somewhat in 5-10 years. I really lose hope with life. If I can get 10-20db increase in my hearing, that would be fine. More would be even better.

I'm sorry jdjd09, but don't expect even if this therapy becomes a real deal to have it bring you back any sort of frequencies you lost. This gene therapy is an approach that is much more for those who were born deaf or have terribly poor hearing. I remember reading that Novartis was hoping that being successful in this therapy would allow some hearing to generated but mainly so that hearing aids can be used to improve the treatments end results. They aren't expecting this therapy to bring all frequencies of hearing back to a human being. You gotta realize too, the specific auditory nerves of our hearing are what allow us to hear frequencies much more clearer, louder, and more emotionally. It's seems to be the afferent nerve that is needed for a full effect of healthy hearing for the brain. Ingoing and outgoing nerves (connected to the brain by spiral ganglion neurons) make up the auditory system. They really are the most important behind the scene pieces of what we call "hearing" We lose these nerves as one ages and the loss can even be sped up immensely from loud noise. New ones, which don't function like the old ones replace the lost degenerating nerves.

I know you damaged your hearing from headphones but it's just headphones really shouldn't damage the hair cells of the cochlea. The hair cells are meant to bend back and forth as sound waves funnel through the three main areas of the inner ear. It was more likely you had excitotoxicity happen. Trust me when I say that it's the auditory nerve fibers that allow us to clearly hear sound waves. They are much more susceptible to damage. Yes the hair cells pick up the sounds, but its our brain neurons that allow us to hear those sounds the way we should.

 

[Reinier]

They aren't expecting this therapy to bring all frequencies of hearing back to a human being.

I think that it is most important they can demonstrate that regeneration in people is working like it is in animal models.
This very important first step should pave a way to refined regeneration. Especially because than we will have people that are able to explain what they hear.

I also believe that there is a lot more to repair than hair-cells. Especially because this is my personal experience. My left ear has very mild hearing loss. Yet complex sounds are also a problem for this ear. And this happened after my NIHL, for sure!
By the way: last year a 10-15 year time frame was mentioned a lot. This year it should be 9-14 years.
I know, silly joke. (-;

 

[Nick Pyzik]

I think that it is most important they can demonstrate that regeneration in people is working like it is in animal models.
This very important first step should pave a way to refined regeneration. Especially because than we will have people that are able to explain what they hear.

I also believe that there is a lot more to repair than hair-cells. Especially because this is my personal experience. My left ear has very mild hearing loss. Yet complex sounds are also a problem for this ear. And this happened after my NIHL, for sure!
By the way: last year a 10-15 year time frame was mentioned a lot. This year it should be 9-14 years.
I know, silly joke. (-;

Actually I think I should rephrase what I posted above to, "this therapy will bring back frequencies, but you aren't going to automatically "hear" better with this regeneration. We need plenty of auditory nerve fibers located on each hair cell frequency to pick up and process sound waves in a normal and healthy hearing way."

The precisely specified neurons of our "hearing" are what amplify sound.

I agree Reinier and I like how you're thinking in that last sentence of your post. Very positive.

 

[RB2014]

I think that it is most important they can demonstrate that regeneration in people is working like it is in animal models.
This very important first step should pave a way to refined regeneration. Especially because than we will have people that are able to explain what they hear.

I also believe that there is a lot more to repair than hair-cells. Especially because this is my personal experience. My left ear has very mild hearing loss. Yet complex sounds are also a problem for this ear. And this happened after my NIHL, for sure!
By the way: last year a 10-15 year time frame was mentioned a lot. This year it should be 9-14 years.
I know, silly joke. (-;

Not sure if this could apply to you, but when I began wearing hearing aides I only used one in my right ear. Eventually after about 10 years I ended up using them in both ears. What happened was the even though my left ear was working, I also lost the ability to hear complex sounds and distinguish words as my brain now relied on my right ear only for so long. I can hold a conversation on the phone with my ha on in my right ear. My left ear has maybe a 20 percent accuracy rate with my ha on.

 

[Reinier]

@RB2014 Is your left ear OK?
I am pretty sure that using a hearing aid in my right ear it will make discomfort only worse. At the moment I am suffering form hyperacusis. Using a hearing aid in my left ear is not sensible (if I am not mistaken). There is very little loss in my left ear when checked with the standard audio test. So what do you amplify in that case? Compress perhaps?
I know that it is not difficult to compress and limit certain frequency bands in a hearing aid. I know that compression is able to make sound more intelligible. But is this the case for more than one person talking to you?

What I experience with my "good" ear is that I hear single or non complex sounds without difficulty. Human voice I regard as complex sound. Listen to lyrics in music, the same. More than one voice at the same time.....well. This is the reason why I put a lot of stock in the "hidden hearing loss" research.

But. I am open to ideas other than my own. When my neurostimulator therapy is finished I will look into hearing aid for my right ear and experience it first hand.

 

[Reinier]

I agree Reinier and I like how you're thinking in that last sentence of your post. Very positive.

Before you know it another year has past. Time flies when you are having fun.
But I am not having fun at the moment
Yet....Looking back always gives you the idea that time goes by so fast.

 

[Nick Pyzik]

Before you know it another year has past. Time flies when you are having fun.
But I am not having fun at the moment
Yet....Looking back always gives you the idea that time goes by so fast.

I'm not having any fun either Renier. It's awful. But sooner or later your brain adjusts itself and you become better at coping with your situation. All we can do is keep moving forward, have patience, and try contributing to the race of finding treatments and discovering more about our sense of "hearing".

 

[Reinier]

All we can do is keep moving forward, have patience, and try contributing to the race of finding treatments and discovering more about our sense of "hearing".

Absolutely. Well said!
I volunteered for a study where people with tinnitus and hearing loss undergo MRIs to see what is happening in the brain. I do hope I will be one of the "subjects" so I can contribute in a small way.

 

[Nick Pyzik]

Absolutely. Well said!
I volunteered for a study where people with tinnitus and hearing loss undergo MRIs to see what is happening in the brain. I do hope I will be one of the "subjects" so I can contribute in a small way.

That's perfect Reinier! I hope you get chosen. Message me if you do get picked.

 

[vaka]

Hello Everyone, i am following this thread for a long time. I know everyone is waiting whether genvec continues its trial or not. So today i came across the following business news from the 21st of march

GenVec Inc (NASDAQ:GNVC) continues with the Phase ½ trial of itsCGF166 in patients suffering from severe hearing loss. The management projects that the trial will complete in 2017 just as was previously expected.

This is the link: "http://www.journaltranscript.com/20...ing-usa-inc-otcmktsgmui-turns-to-acquisition/"

maybe someone is able to verfy or disprove that.

 

[Reinier]

Who knows what dose escalation phase is? I read this in the link @vaka sent.
The following I found in an article.
Quote: "The guiding principle for dose escalation in phase I trials is to avoid exposing too many patients to subtherapeutic doses while preserving safety and maintaining rapid accrual"
End quote.
So the reason GenVec paused was because dose escalation was reached?
Just interested.

 

[Aaron123]

The issue is determining the volume of the drug that can be safely delivered to the inner ear as well as (presumably) the dose.

They did a single cohort of 3 people for safety at a volume of 20 uL Then they were doing a series of five 3 person cohorts with increasing volumes from 20 uL up to possibly 90 uL They paused after 9 people were enrolled so they made it through two rounds of the dose escalation. According to the protocol, they did a safety review after the first patient in each dose escalation round and then a "full cohort review" after each 3 patient cohort. We don't know if there was an issue with a higher volume or if something came up from the earlier rounds.

There's a lot of information about the trial in the pdf I posted above. See pages 18 and 19 in particular.

 

[RB2014]

I am going to remain optimistic. I still say that if something bad had happened, it would be a cancellation and not a pause.

Reinier, yes a hearing aide would be bad if you have hyperacusis. I had hyperacusis for a while, but I am over it now. It was my fear and anxiety that gave it to me. Once I was able to get control of the fear and anxiety the hyperacusis went away. It took months though for this to happen.

 

[Reinier]

Once I was able to get control of the fear and anxiety the hyperacusis went away. It took months though for this to happen.

My hyperacusis must be part anxiety. I absolutely hate it when normal sound levels already distort (crackling). It is almost 10 months for me since the onset of tinnitus, distortion and hyperacusis. I hope distortion at normal sound levels will eventually go away, but starting to doubt this. Than I think my anxiety severity will be a lot better and I will not be unhappy when I am nosey (read normal sound levels ) environments.

News like the continuation of GenVec trial therefore is much needed good news.