Denver Man Gets Gene Therapy to Restore Hearing

Phase 1 and Phase 2. Normally a Phase 1 trial uses healthy volunteers. Given the invasiveness of the procedure and the fact that the goal is regeneration, it doesn't make sense to use healthy volunteers. The first 3 people in the trial were essential a safety cohort. That is, as I understand it, the first part of the Phase 1 component of the trial.

After the safety cohort, they began varying the doses. This is second part of the Phase 1 part of the trial. In other words, the main goal here is safety though they would of course monitor outcomes. Unless something has changed, there are to be 4 cohorts of 3 people. (I believe it was during this part of the trial when the trial was paused.)

Finally, there is the Phase 2 part of the trial with 20 patients. The dose is presumably based on the second part of the Phase 1 component. This is the efficacy phase. There is no placebo arm of the trial.

Thus the total size is 45 people. As of early February, they had enrolled 11 patients. It's not clear how soon we will know any actual results of the trial. If we have to wait for them to enroll 45 people, we seemingly have a long way to go.

Not sure what results you or she meant. It is possible some results will be released by the end of the year, but given the difficulty they are apparently having with enrolling patients, it seems very unlikely that the final results will be available for some time.

 

Good point. I guess I don't know much about satistis. I guess I was just thinking about a small pool of people. They need a larger pool to show anything my bad.

 

If you ring the centres and ask about results they think you are a broker and try and wind up the call. They have been briefed on the importance of data protection. There will be a lot of jealous investigators if Staecker comes up with the goods. I see Albert Edge is now launching a similar human phase 1 for end of summer 2019, he was all mouse and gerbils till he saw cgf roll past him. Interesting how when one lab makes a move the others panic and rush to human trials. A lot of these drs have their own cash in their own projects, Swirsky himself has put an absolute fortune into genvec from his own pocket, details like that matter a LOT.

 

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GenVec Shareholders Sue Over Intrexon Merger
By Cara Salvatore

Law360, New York (March 29, 2017)



Gene therapy research company GenVec Inc. was hit by a putative class action Tuesday in Delaware federal court by shareholders who say the company’s imminent acquisition by Intrexon Corp. gives them a raw deal and that the merger registration statement is inaccurate.
GenVec shareholder Paul Parshall says the merger with Intrexon, announced in January, was rushed through with inadequate analysis, gives shareholders too little relative to GenVec’s actual worth, and involves an incorrect SEC registration statement. Intrexon is also listed as a defendant, as are a number of GenVec insiders.

Intrexon, which deals with the engineering and industrialization of biology, announced in January it would buy GenVec, a clinical-stage company working to develop gene technology. The all-stock deal will see each share of GenVec swapped for 0.297 share of Intrexon’s common stock, which values each GenVec share at about $7, according to a statement at the time.

“The consideration to be provided to plaintiff and the class in the proposed transaction is inadequate,” Parshall’s complaint says. “Among other things, the intrinsic value of the company is materially in excess of the amount offered in the proposed transaction.” The deal also lowballs the benefits that will come from the combined companies, it says.

Representatives for GenVec and Intrexon were not immediately available for comment on Wednesday.

Intrexon stock has fallen since the announcement, Parshall says. It had been trading around $22 but has since fallen to about $19. That changed the trade ratio that was laid out in the deal.

The Intrexon stock drop means GenVec shareholders are actually receiving less implied value for their stock than they could get from selling it on the open market, they say.

And yet “the board failed to negotiate for a collar that would protect GenVec’s stockholders from this foreseeable decline in Intrexon’s stock price,” the suit says.

The shareholders will also split half of milestone payments made by Novartis for three years under a licensing deal for a hearing-loss and balance gene therapy that’s in clinical trials.

The merger’s SEC registration statement is also false and misleading, according to the suit.

One significant alleged hole is the lack of mention of $253 million in carry-forward tax loss offsets available for GenVec to use and whether those were factored into the financial analysis of the adviser that the board eventually did hire.

A leader at GenVec accepted the offer without asking the board and the board eventually approved the offer without consulting a financial adviser, the suit also claims.

Parshall says the defendants have violated Sections 14(a) and 20(a) of the Securities Exchange Act of 1934 and SEC rule 14a-9.

Parshall is represented by Brian Long, Seth Rigrodsky and Gina Serra of Rigrodsky & Long PA and Richard Maniskas of RM Law PC.

Counsel information for the defendants was not immediately available.




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source: goo.gl/VEf5ns

Does Paul P@rshall know something we don't?



I'll post the court docs when I get them.

 

i pasted that case report in case you just got the paywall pop up on the site.

 

I don't know all of the details, but Genvec investors have been unhappy about the deal with some particular thought that the CEO and other officials are doing well at the expense of investors.

The prospect of milestone payments for the Novartis trial just got pretty bleak with the delay in the completion of the trial until 2019.

Will be interesting to see what happens.

 

I agree entirely.

 

P@rsha11 v. G3nvec, Inc. & others, court filings as of 3rd March 2017

goo.gl/cerx4v
That link will be dead in 72 hours, so grab it now and read later if you are interested.

 

From what we know, the procedure didn't work on Rob Gerk plus one other person. I hope the investors weren't holding out hope for any payments from this working. It was a good first shot at a hearing loss cure and a good proof of concept that no one got any adverse affects from it. Based on what I know I wouldn't sign up for the next trial and I am pretty close to being eligible. They may not be able to find anyone willing to risk whats left of their hearing on this one.

 

Then why are Intrexon trying to push the buyout to occur before the trial results are released.

 

Ok you guys, we need more information about this I believe they don't want to let the cure out , people have had it for 50 years , so ask your self are they really looking , money will be lost for all ent doctors and hearing aids doc, not to mention money on drugs for anxiety and depression, not being negative just thinking about it, but how could they do this to us , even all these vets that are coming from serving our country, they just give them disability and adios, God help us and friends and relatives, so many people spend so much money on trips and hair cell and stem cell therapy and nothing, I would like a respond to this what do you really think, only God willing will take this away from us , I believe mine was from self induce, listening to music on my tablet which was loud maybe but you see people all day with ear buds and headphones and nothing , just can't believe the GREAT UNITED STATES OF AMERICA CAN NOT FIND
Something or try something they just talk nothing worst than seeing your ent and they say sorry can't help, I need a respond please what do you guys thing , they say don't eat this and that, not much of a difference, I don't eat hardly any salt do to heart surgery or caffeine just a soda and caffeine free here and there and tea , alot of water and food well you will be losing alot of weight if you follow what alot of people say here , so I am bewildered about all of this, you get scared to eat anything and all these scams that are out there , a guy use garlic cloves in his ears as he slept and it went away well I tried it and nothing , acv tried it to , please some one here tell us what really work, AMEN AND GOD BLESS US ALL, somebody please let's talk .

 

I wish you were right, but I'll counter with why did Jeff in KS get a cochlear implant shortly after he lost the rest of his hearing after the procedure, and why did Rob Gerk show no results from the procedure.
I wonder if they want the gorilla vector they have, but even from reading it seems like there might be better vectors out there right now.
I'm not really sure what to think. I wish there was more information out there so we wouldn't have to speculate so much.

 

Part of me wonders if the delay is because they want to try the much more advanced Anc80 viral vector that was only broken to the public in January (which was a harvard discovery). in short the "supercharged" aav that is wrapped in bubbles instead and has far superior results. Who knows, could also be the shorted in patients that they have had (11/45)

 

See Below:

Yes, I did hear about that gentleman losing virtually all his hearing. It makes me more concerned about the safety of the surgical entry than it does about whether the actual vector itself is dangerous. The inner ear is "arguably" the most difficult area of the human body to perform surgery on and the risks are high, even in simple procedures. It is a surgical "minefield", facial paralysis and deafness are common after schwannoma removals. I would point out (before I write anything else) this trial upon completion MUST show objective tests before and after dosages that will be scrutinised by peers in otology, and they will be absolutely savaged for artifacts, just like Geoff Raisman was after his oec first in man model. It is really these "numbers" that will reveal all. Each trial location is using Øtometrics testing equipment, this is important as they produce inarguable test data with few artifacts. If there is a change in peripheral hearing or balance, they WILL find it.

As for Rob Gerk, which dosage level do you think he received? Have a guess.
See Below:



You yourself posted this, did you forget the article?
https://www.tinnitustalk.com/threads/ku-gene-therapy-holds-new-hope-for-restoring-hearing.12258/

Quote from the article

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"Amanda James first noticed a difference early this year when she picked up a pill bottle at the Norfolk, Va., pharmacy where she worked and shook it next to her right ear.
For the first time, she could hear the pills rattling inside.
But after receiving an injection directly into her right inner ear as part of a study at the University of Kansas Hospital, James seems to be slowly regaining some of the hearing she lost.
The results so far have been “amazing,” she said.
“It’s something new each month. I can hear music. I can hear your voice, but I can’t make out the words yet.” "
-----------------------------------------------------------------------------------------------

I presume you also read this interview with Lustig?
http://www.hearinglossjournal.com/cgf166-latest-news/
Quote from the article:
“There have been a couple patients with hearing improvement, so we are definitely encouraged.”



You said Gerk had no results from the procedure, but that is not what I heard him say, if you listen closely to his interview he comments on his balance, peripheral balance fucntion when damaged (like hearing) does NOT spontaneously recover, that is impossible. What he said is very unusual. Also I know that Rob Gerk is not the only person who has reported their balance changing. So I await that trial results with anticipation.

Remember all we need is a shred of objective data that shows recovery of function and the whole research arm will become a frenzy of investment. As for the other vectors you mention, they are not in human trials, as such they do not interest me yet.

Also, do you think that Intrexon have seen the patient data from the cgf trial? Do you think a biotech trading at 20 dollars would not have asked for this before making an offer like that to merge?

 

You make some good points. I guess I only zeroed in on the negative results or the negative portions of the articles. The difference between Jeff , Amanda and Rob could have been the dosages. I have never read where we find out which dosage any of the participants got. This could be a factor in the success or failure that some participants had.

Jeff also has a history of hearing loss in his family which points to a genetic defect. This could be a factor as well. Amanda lost her hearing from what I remember in a swimming accident when she was younger. Rob I think had a different cause, spinal meningitis. This might also only work on a specific type of hearing loss cause. Amanda's hearing loss was more typical than the other two and could mirror the typical person that goes to too many rock concerts or loses his hearing through age. Maybe this type of procedure doesnt work on people with genetic defects or diseases that caused the hearing loss.

Rob did mention his balance improving, but he did not mention hearing getting better. I am agreed, this is unusual. Amanda mentioned being able to hear words and not understand them. This was also a red flag to me.
Jeff actually lost the rest of his hearing in that ear after the procedure. This was the most disturbing to me.

I don't think Intrexon has seen the patient data. They could be speculating from the positive reports that came out, but who really knows.

I think now what they need to do is analyze the data and figure out what it was about the specific patients that recovered their hearing had in common. Was it the dosage? The type of hearing loss? At this point all we can do is speculate until the results come out.

 

I didn't know Jeff had a genetic predisposition. It is a cruel fate to inherit. All of us can relate to focusing on negativity with regards to "T". I can only hope that competition within the research arm translates to clinical application fast. You raise a fair point as to what level of architecture must remain within the organ for these early cell therapies to have an effect. It may well be the case that some levels of damage will leave nothing but an empty space in the skull with no cells even left to repair. One thing that patients become upset at is the strict trial screening, if you look at Geoff Raismans trial he had to verify disconnection of the spinal cord and full physiotherapy engaged by the subject BEFORE he could argue that it was his therapy that regenerated the tissue. I imagine that a key part of future trials of ear repair will seek out those patients who have had a surgical deafferentation so that it cannot be argued that some sort of unknown spontaneous recovery occurred. Even if cgf shows results, there will still be many who refuse its claims. This is why you must try to set up your trials to be as watertight as possible to withstand the barrage of criticism that success inevitably brings in medicine. Also the risks for the repuation of cell based trials, gene therapy had very bad press not so long ago, the world has not forgotten Jesse Gelsinger. Opponents of stem cells and technology use these stories to slow progress for their own agenda. I have even encountered members of the deaf community who describe trials like this as "evil".

 

http://entcolumbia.org/world-s-first-gene-therapy-trial-hearing-loss

 

Great news!! Thank you. When was this published? I find it very frustrating when web articles don't contain bylines!

 

Looks like it could be from February 2017, judging by this article: http://www.hearinglossjournal.com/cgf166-latest-news/

The results so far are promising. “There have been a couple patients with hearing improvement, so we are definitely encouraged.”

 

This sounds promising, but the procedure also sounds a little scary!

 

You seem a bit off on a lot of things, but you're absolutely correct; there's no corporate interest in curing hearing loss. Luckily in the US over the counter hearing aids have been made legal and this should force the price down. If you're right we should "magically" see some sort of treatment come out soon, because that's all they have left.

 

The hearing aid companies are not in some conspiracy for alternative therapies to fail such as gene therapy, regenerative medicine. It's a free market! If a company comes up with a 'cure' they will wipe the lot of them out. Good luck to them!

 

Exactly. There is no "one big health care company" with one interest, hearing aid companies and the like will compete against those developing/providing a cure. Then there is a government interest in favor of finding a cure, which could be coming from a welfare state model, or from trying to the reduce the number of citizens needing social security due to tinnitus.

A conspiracy among institutes to refrain from researching a cure is pretty much impossible. There are too many institutes doing research all over the world. And there's high chance that such a thing would leak, and if it did, it would be a huge scandal.

 

@walkthroughwalls There have been people who reported improvement? Do you know any specifics? thanks

 

I was quoting from the article I referenced, and that's all I know. I'm not sure how reliable the source is, though.

 

I assume you are all aware of the Stanford initiative to cure hearing loss in 10 years. If not, here's a link https://hearinglosscure.stanford.edu/ I don't understand why they are talking about cures being so far off but the Novartis virus gene therapy is here now. I'm confused.

And on a side note, I watched all of Robert Jackler's presentations and he is so inaccurate with his claims. In the 2012 video he says 10 years. In the 2013 video he says 10 years. In that same video he says, if you ask me again in 5 years, I might say the same thing. What the heck? Why even say 10 years to begin with if your gonna keep changing your mind. lol

 

Jackler (whilst heading the group) is not the most talented "pure" researcher. He is a clinician first and foremost. I would listen more to Ricci, Heller and Grillet.

 

When do these guys think a cure or an effective treatment will come

 

Yes, that trial is indeed happening now, but since the estimated completion date is June, 2019, I wouldn't expect any information on results (either positive or negative) until early 2020... if it's not delayed again. If successful, I believe they will look for another delivery method.

By the way, it is not proved that "curing" hearing loss will also cure tinnitus.

 

I wonder if this would work on less damaged ears as well. Anyone know?