Novartis Pauses Study of GenVec's Gene Therapy CFG166 (UPDATE May 2016: Trial Is Again Continuing)

They reduce supporting cells instead of duplicating them.

I also hear unconfirmed claims that the hair cells regenerated do not have the same natural shape/structure as natural ones.

 

The thing that I don't like with gene therapy is that it activates a gene but this doesn’t take into account all the other genes of the inner ear as knowing all the genes of the cochlea would take forever. If you activate a gene that produce hair cells, it will produce hair cells all the time which can lead to a tumour, naturally for the birds for example there must be other genes controlling the first gene to make sure there are not hair cells produced without control.

PCA divides and multiply support cells whereas the gene therapy doesn’t and the hair cells only grow the time of the gel is in the ear so they won't keep multiplying indefinitely, which is safer to me.

 

So why don't they get a move on it, yesterday. Allo.

 

You just gotta keep killing your hair cells.

 

Is this an example of having remaining intact nerves? The regeneration of the hair cells naturally attached to something we debate about everyday. I doubt every person in the trial lost their hearing right before participating in the trial.

 

Three questions:

1. Trial updated 12th Nov. Anybody know what was updated? https://clinicaltrials.gov/ct2/show/NCT02132130
2. If the trials are recruting, is anybody here trying to get in?
3. Does this method "use up" the supporting cells that FX322 is targeting? Meaning you will not get help from Fx322 to restore more hearing if you have used this drug already

 

Here are the changes from previous version:
1)They added following under Study Design:
Allocation: Non-Randomized
2) Changed wording of 2nd point of inclusion criteria (looks like pure technical change)
3) Changed 4th point of inclusion criteria. Here is old version:
Candidate ear ("study ear"): Pure tone audiometric thresholds of ≥50 dB HL for each testable octave frequency of 0.125 and 0.250 kHz, ≥ 70 dB HL for each testable octave frequency from 0.5 through 8 kHz and sentence recognition scores ≤50% at screening. Subject responses will be monitored for vibrotactile sensation, particularly for the low-frequency stimuli (e.g., 125 and 250 Hz). A frequency that elicits vibrotactile responses at levels below 70 dB HL will be considered "not testable" for hearing threshold and only those frequencies that are testable for hearing threshold will be considered for patient inclusion/exclusion in the study.
4) Added new location:
Oregon Health & Sciences University Recruiting
Portland, Oregon, United States, 97239
Contact: Eleni O'Neill 503-494-3569 oneilele@ohsu.edu
Principal Investigator: Timothy Hullar, MD

Finally some good news from this trial. They were in talks with FDA to ease inclusion criteria, apparently this is a result. I think very strict inclusion criteria where the major hurdle in the trial.

Hope they can make it work, at least I have more hope in CFG166(with Novartis behind it), then in Frequency Tx(20 employee garage company, where half of the employees are on their web page with all the fancy job titles, like CEO, CMO, CFO and so on). That would be a real miracle if FX could deliver any drug to the market.
(sorry for the off-topic, and not that I don't want them to succeed, but I just cannot stand constant haling of FX in every thread with no factual basis whatsoever).

 

Do you know what trial they're on?

 

"The procedure involves going down the ear canal and detaching the tympanic membrane (ear drum) to reach the cochlea. A laser is used to create a hole in the cochlea to deliver the CGF166"

https://www.hearinglossjournal.com/cgf166-latest-news/

 

That sounds like it hurts.

 

Yeah, also sounds like relatively large risk of lasting conductive damage.

 

This is interesting. I work with Timothy Hullar MD.

 

"Work with" as he is your doctor, or "Work with" as in a professional setting?

If you can glean anything from him many here would appreciate it (Like results so far)

 

I work with him at OHSU. I'm not a patient of his. I didn't know he was involved with this.

 

Why?

 

They "detach the tympanic membrane", I would think that something as drastic as that would carry relatively high risk of at least some permanent conductive damage. Even common grommets (which seems less impactful than eardrum detachment, though I could be wrong) have a minor controversy about causing a (relatively small) amount of conductive HL (http://mobile.nytimes.com/2006/08/15/health/15brody.html).

 

Cool! Not sure how much he can say, but maybe you could ask him:
* Does he know of FX 322? What does he think of that vs CGF166?
* Does any of the patients in the trial have tinnitus ? Has the drug had any effect on the T?
* Why the long follow up? CGF166 is running for years and FX322 trial is just has 3 months...
* He might be under an NDA but... how promising is the drug? Does it cure in 20% of cases or 80%?

Or anything else that he can share. It's the first hearing regeneration trial ever, he must think its pretty exciting!

 

Where, in the article you quoted, does it say that grommets cause permanent conductive HL?

Are you talking about "while you have the tympanostomy tubes in" or "permanently" (ie after the tubes are gone and the drum has healed)?

 

I'm talking permanently. Here's the relevant quote from the article I linked:
"According to a new long-term study by Dr. Stenstrom and colleagues, when young children were randomly assigned to receive ear tubes or to be treated daily with antibiotics, those with ear tubes suffered greater damage to their eardrums and had, on average, poorer hearing 6 to 10 years after the tubes were removed."

 

Thanks! I think the study they are talking about is this one: https://www.ncbi.nlm.nih.gov/pubmed/16330739

Indeed damaging the ear drum physically is probably not going to make it work better than keeping it intact, but I'm happy to see some quantification of the decibel losses.

It's always tricky to determine go/no-go on tympanostomy tubes. We did it for our daughter because she had recurrent ear infections to the point of bursting her ear drum twice in just a few weeks. At that point, it seems like you have to chose between a "controlled hole" vs a random burst damage, and there's really no good choice either way. I imagine a burst isn't much better than a surgical hole in terms of long term damage.

It would have been good if the study also took a look at the effects of constant antibiotic use for the subset that did not undergo tube insertion, because that's a parameter that is important for the trade-off: we were giving our daughter antibiotics over and over again, with just about 10 days in between treatments where she was antibiotic free.

Of course, now we have to deal with the fallout of the tube decision (no pun intended): in one ear, the tube just fell out on its own (it was taken out of the canal just yesterday), but in the other ear, it didn't and is starting to tear another unexpected hole in the ear drum, which means we will need to do surgery pretty soon to extract the tube & patch/repair the ear drum. Ugh!

 

Well, according the quote from the NYT article the control group was treated with antibiotics, although yeah it's unclear how often.
Too that JAMA article itself mentions that the control group received "medical" (I.e. non-surgical) treatment although oddly I see no description there of what said treatment consisted of. Weird cause I assume you're right that that study is the one being referenced in the Times.
I researched this when I was looking into having ear tubes places to facilitate HBOT months ago... Crazy.
Is your concern with antibiotics potential ototoxicity?

 

Ototoxicity is one issue, but I'm not obsessed with it. Antibiotic resistance is another one. I imagine being constantly under antibiotics isn't that good for your body in the long run...

 

I was waiting because I heard that the research will be completed on October 9th. I don't have any news. Will the presentation usually take place a little while after the research is completed?

 

I am calling the Oregon Contact tomorrow. It states the trials are recruiting, but I can't find any additional evidence of that on the web.

 

What trial are they on?

 

I think phase 3, but I will find the info and report back.

 

Thank you! God I hope it is phase 3.

 

I think it’s tranche 3 of Phase 1/2. Reason for the tranches is probably so the FDA can sharply monitor the trial. There have been issues with gene therapy trials in the past.

 

How many more trials are needed until it can be released onto the market??

 

Usually they do a Phase 1 (or Phase 1/2), then Phase 2a, 2b and 3. There’s also a Phase 4, where they have to monitor the drug after it’s released on the market.