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

Any news on CFG-166? Estimated trial completion date was December 5th.

 

Still nothing on their website or the ClinicalTrials.gov page...

 

Probably takes some time to officially report results, but this therapy was not at all on my radar so it’s nice to see that there’s another player in this game that (may be) close to reaching the market.

 

Not so good news. This trail is suspended again:

https://www.hearinglossjournal.com/novartis-suspends-cgf166-trials/

Remember: CGF166 is delivered by a small surgical operation where the eardrum is temporarly shifted aside. Not a very attractive treatment but it is intended for people with profound hearing loss. Again little is known about the exact results achieved until now.

 

A few of my thoughts of the problems with this:

This procedure uses a cochleostomy to insert the medication, which causes enough inflammation to be very destructive to hair cells, sometimes widely.

There is a newer surgical method for delivery of AAV involving a canalostomy. This procedure is completely safe for the cochlea. It would be great if they could switch over to this method.

Very severe to profound loss means you have little to no support cells left, which means there is no substrate for the drug to act on. The ones who benefited likely had less severe audiograms.

I am willing to bet when they restart they will cap the thresholds around 70dB-80dB losses.

 

Has anyone seen this? It's the results from the Phase I/II, posted on March 30th.

Safety, Tolerability and Efficacy for CGF166 in Patients With Unilateral or Bilateral Severe-to-profound Hearing Loss

I have no idea how to read this. Of note is that they tested up to day 600! That's nuts.

 

It looks like the best dose is 40 µg. However, one person acquired tinnitus at this dose.
Study ended at day 600 but published tests were done at week 52 (no published tests at day 600).

Still no report from Novartis itself:

https://www.novartisclinicaltrials.com/TrialConnectWeb/aboutresult.nov?studyid=54904

 

I'm not sure how to read this. It does look like the 40 µg dose was most effective if I'm reading this correctly:



Particularly for lower frequencies, which would make sense since their surgery was really inflammatory/destructive for higher frequencies especially it seems. Also possible they were in the more severe range (vs profound) in that range and their drug transduces support cells, not fibroblasts.

I wonder if they plan to retry and change their delivery method/surgery.

 

Couldn't they just inject their goop with an intratympanic injection?

That delivery method seems very counterproductive.

 

No. Viral vectored therapies have to be directly inserted into the cochlea. That's a big problem with them. Akouous has come up with a new surgery though involving Stapes venting which is less destructive.

 

Those procedures are going to be a Hail Mary if intratympanic injection therapies get FDA approval.

 

I'm trying to interpret these results, but I can't.

Basically it recovered over 20 dB on the low frequencies and little, or even nothing, on the high frequencies?

Has the research been completely abandoned or is it still ongoing?

 

It seems like a 20-30 dB recovery in the first 3 frequencies (low frequencies) but there is no recovery in the other frequencies.

I think if there was a 20-30 dB recovery in all the frequencies, they would go for further steps. But what I understood is they thought these gains are not worth the risk of the surgery. I wish there was a more safe method for injecting the drug.

 

I don't understand it really, why can't it just be injected through the eardrum, or is it different from the drugs by Otonomy or Frequency Therapeutics? I understand that back then there weren't proper delivery methods, but c'mon guys, we got them now, use them please.

 

Could they go through the Eustachian tubes and enter through the window membrane? Using some time of catheter?