Sensorion's New Drug: SENS-401

it's also probably to control the doctor's reaction. Double blind.

 

Here is the content of the abstract submitted to the SfN meeting. I was at the meeting but did not see their poster.

710.03 - Significantly improved recovery of severe noise-induced hearing loss by the orally available, clinical drug candidate SENS-401
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Author Block: *J. DYHRFJELD-JOHNSEN, M. PETREMANN, L. BEYNAC, A. BROUSSY; Sensorion SA, Montpellier, France
Disclosure Block: J. Dyhrfjeld-Johnsen: None. M. Petremann: None. L. Beynac: None. A. Broussy: None.
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Sensorineural hearing loss through acoustic damage to the sensory hair cells, synapses and neurons of the cochlea is among the most common types of permanent hearing loss for adults (American Speech-Language-Hearing Association - ASHA; Hearing Loss Association of America - HLAA). Currently no approved pharmaceutical treatment exists for sudden hearing loss and recent meta-analysis of the standard-of-care, off-label use of corticosteroid therapy have concluded that neither systemic nor intratympanic administration has any significant treatment effect (Crane et al. 2015, Laryngoscope 125(1):209-17).
SENS-401 is small molecule, clinical drug candidate which can be administered orally and achieves significant local exposure (50-250 nM) in perilymph and inner ear tissue lasting at least 6 hours after a single oral administration in naïve rats.
Following baseline audiometry (ABRs at 8/16/24 kHz; DPOAEs at 4/8/16/24/32 kHz), 7 week old awake and behaving male Wistar rats were exposed to 120 dB octave band noise (8-16 kHz) for 2 hours on a slowly rotating platform in a sound-attenuating cubicle. SENS-401 at doses of 5 mg/kg, 10 mg/kg and 20 mg/kg or placebo treatment was initiated after the end of acoustic trauma exposure using oral gavage continued daily for 14 days.
In animals suffering initial severe hearing loss (ABR threshold shifts > 55 dB or otoacoustic emissions detectable only at 2 or fewer test frequencies at t=24h), daily SENS-410 treatment dose-dependently reduced permanent ABR threshold shifts from baseline to D14 from 52.1-59.3 dB in the placebo group down to 33.3-49.2 dB in the 2 highest dose SENS-401 treated groups. This corresponds to an improvement from &8220;moderately severe&8221; to &8220;mild/moderate&8221; hearing loss according to ASLHA criteria. ABR threshold recovery from 24h to D14 was also dose-dependently improved from 7.1-12.9 dB in the placebo group to up to 20.8-29.2 dB in the 2 highest dose SENS-401 treated groups. DPOAE amplitude recovery from 24h to D14 was similarly dose-dependently improved, with placebo treated animals particularly showing near complete and permanent loss of otoacoustic emissions at the most sensitive, higher tested frequencies (16/24/32 kHz), while SENS-401 treated animals showed partial recovery in the 2 highest dose groups.
These results demonstrate that daily, oral administration of the small molecule clinical candidate drug SENS-401 leads to significant local drug exposure and strongly enhances recovery in rats suffering from severe, acute noise-induced hearing loss.

 

This is excellent news.
Is it not??
Also the fact that oral administration is used and effective. A molecule that is able to end up in the inner ear!
"These results demonstrate that daily, oral administration of the small molecule clinical candidate drug SENS-401 leads to significant local drug exposure and strongly enhances recovery in rats suffering from severe, acute noise-induced hearing loss."

Could this be a first step. Treating acute NIHL?

I would love to see some comments from people that are more knowledgeable than I am.
This is too technical for me to comprehend its significance.

 

Autifony also demonstrated a successful effect in rodents. I would take any result that is only preclinical with a grain of salt.

 

Jesus Christ... a little bit of positivity????? FFS!

 

More positivity is indeed appreciated as we have to overcome the long wait. The precursor SENS-218 is in a phase-1 study. That makes it a little bit more positive. I hope they find some more molecules...

 

I would think that it is quite an accomplishment to get an orally administered drug to end up in the inner ear.
I always read that that was very difficult because of the blood/inner ear barrier.
Also this molecule apparently has an effect. I would Imagine this molecule reduces the damage that happens short after a noise incident.

 

Yes, it is encouraging (and somewhat surprising) that this compound, taken orally, can accumulate in the fluid-filled compartments of the inner ear.

I'm not seeing very much on the mechanism of action for this compound. Presumably, it is an anti-inflammatory drug but I'm not certain.

DPOAE is a measure of outer hair cell function. Outer hair cells power the cochlear amplifier and helps restore auditory brainstem response (ABR) threshold sensitivity. They did not test any behavioral assays that would indicate hearing status or tinnitus intensity. Those are harder to do (properly, at least) in rodents.

Results like these have been described and published many times in animal models. However, achieving this kind of effect is less common with a drug that is taken orally. So that is encouraging. The trouble is that these studies are almost always done by administering the drug shortly before or just after the intense noise exposure. This does not model the situation with chronic hearing loss and tinnitus. Recovery of function with this class of drugs is far more limited if the they are administered just a few days after the injury.

Still it's a step in the right direction. There are so many drug companies focusing on hearing protection and hearing recovery these days. More than ever before. That is very encouraging because biotech companies act as an accelerant to discovery. With that said, fewer companies are willing to take on the harder case of chronic hearing loss and subjective tinnitus. Also, my bias is tinnitus won't be solved by any research lab or drug company that is only focused on the ear. It is a disorder of the brain.

 

Not quite. There is proof that it's not always a disorder of the brain (when Tinnitus goes away after a stapedotomy for example - which is about 50/50). Not to mention PT.
It really is multi-faceted and complicated, which is bad news for us, unfortunately.

 

Agreed. All of these disorders are multi-faceted. My H for example was a reaction to the fear that I got from getting T. Once the fear when away the H went away. Not everyone is so lucky. Same with T which is why it could be a while before anything comes out or if it does it could be very specific to a certain type of duration of T. Either way, this article is a positive step in the right direction.

 

Some good news is wonderful these days. One of these days the med is gonna be the first of many.

 

I understand. I just hope this will however improve understanding of the process, where the initial damage is not as severe as the damage caused by processes in the inner ear following a noise incident. Or is that already well understood?

I wonder if research has been done if this drug ends up in other areas of the body were it can do harm. Perhaps too early in this research?
I hope they designed a clever mechanism to get certain molecules in the inner ear and that alone could be regarded as a breakthrough. Perhaps that is the bigger step forward in this research? Step by step.

 

How does an ABR translate to a hearing threshold?
For example, an improvement of 20 dB in ABR is ??? dB improvement in hearing threshold?
It probably is not that simple.
Does anyone know?

 

In healthy ears, the connection between ABR threshold (faintest sound that can evoke a measurable response) and hearing threshold (faintest sound that can be behaviorally detected) is fairly close. The problem comes when there is damage to the cochlear nerve without damage to outer hair cells. Then the connection is less direct. In one extreme form (called auditory neuropathy), there might not be any measurable ABR yet detection thresholds can be normal. In other conditions, it can go the other way (trouble hearing with normal ABRs).

The bigger issue is that thresholds of any kind (ABR or audiometric) are a poor indicator of tinnitus, difficulty hearing speech in noise, hyperacusis etc. Better metrics for suprathreshold hearing status are available - and this comes up in many other threads - but research scientists and audiologists are slow to incorporate these tests.

 

[Quote = "GregCA, posta: 215.236, membro: 15807"] Non proprio. Vi è la prova che non è sempre un disordine del cervello (quando tinnito va via dopo un stapedotomia per esempio - che è di circa 50/50). Per non parlare PT.
E 'davvero multiforme e complicata, che è una cattiva notizia per noi, purtroppo. [/ Quote]

Hi Greg; I also have "otosclerosis"; you think that really the % of success (tinnitus go out) of stapedotomy is 50/50 ? You have do the surgery ? Btw 2 months i will do the stapedotomy; my T is bilateral and i will alreary be happy is the tone of T it will be subside;

Thank you and sorry for my bad english !

 

" naive rats " What?lol

 

Hi, King,
The % of success is what I read from medical studies. It is also what my surgeon told me. There is also a small chance to make T worse. Single digit %.

I did have a stapedotomy earlier this year (in April). It definitely helped with my air-bone gap, but not with my sensorineural loss (I didn't expect it would). It also got rid of most of my hyperacusis. It did change my tinnitus, but I still have a nasty one (probably from the sensorineural losses).

 

@HomeoHebbian
Thanks. Much appreciated.
I just can't stop translating these processes in inner ear and brain to similar processes in electronics.
There is input, output, feedback, gain control, signal to noise ratio, phase locking and many more parallels.
I suppose it makes it easier for me to comprehend.

 

Hi Greg; I hope also my T change after stapedotomy ; Have sensorineural loss that is not curable; but also transmissive loss -70db on low frequency that i hope to recovery. Byee

 

Yes the sensorineural loss is not expected to be recovered with surgery, but the conductive loss recovery has a really good success rate.
There are some treatments for the sensorineural part, but they have limited success. At the very least you can try and prevent further deterioration.

 

http://www.sensorion-pharma.com/en/pipeline/pipeline

A phase 2 study is planned for 2018

http://www.sensorion-pharma.com/ima...-06-08-PR_SENS-401_phase_1-results_vf_eng.pdf

I really like this A 5-HT3 receptor can be administered orally

 

SENS-401 drug candidate

During the first half of 2017, the Company successfully completed a phase 1 clinical trial establishing the safety of SENS-401, its second drug candidate.

Separately SENS-401 demonstrated in preclinical testing to have a preventive effect against cisplatin-induced ototoxicity. Sensorion subsequently received Orphan Drug Designation for SENS-401 by the FDA in this indication in a pediatric population and confirmed its objective to develop SENS-401 in this indication, in addition to sudden deafness.

Subject to regulatory authorizations, Sensorion plans to initiate phase 2 clinical trials with SENS-401, to treat sudden deafness and prevention of cisplatin-induced ototoxicity in a pediatric population in the first and second half of 2018, respectively.

 

Their sens-111 is also vague on menchanism. For anyone interested in this compound, see below
They flew a celeb vertigo dr in to "wow" prospective investors at their KOL. One thing I will say about Strupp is that he has the most marvellous hair in otology, I mean it's so thick and luxurious.

Michael Strupp @ K0L (2016)

The reason they are hovering around this disorder for a drug is that there is no competition, there is nothing for neuritis in clinic, so a drug (with even slight proof of efficacy) could be sold globally at high prices to hospitals for this purpose, it would be like fishing with dynamite for a pharma patent.

Interestingly, their share price has not been doing so well of late.

BIO-Europe® 2017: Sensorion seeks partner...

 

Please don't scream about positivity it is much better that we are objective. Go around and being "positive" will make you fall down in despair many times over instead of just once.
The day there is a cure let's talk. So please be objective. No need for "positivity" when it comes to the price of being realistic and critical!

 

This is probably the reason why we are affected by T, I'm usually not the most positive person on earth, mostly tried to be realistic, but then what's realistic and from what I read, being positive also helps to cope better with issues in life. Don't get me wrong, I had a few major traumatic events in my life, and I agree that the reason I'm bothered by my T, while some of my friends aren't is the way I react to health issues in general.

 

It can and will also spiral. Hypochondria is when you care too much. I am myself a hypochondriac and the boring fact is that when you are damaged no matter where on you body the best solution is to accept it. Faster the better.

 

Collaboration between Sensorion and Cochlear to attempt to improve outcomes for Cochlear Implant patients: http://www.sensorion-pharma.com/images/press-release/20171218_PR_SensorionCochlear_18122017_1_EN.pdf

 

And a presentation that provides some additional information about SENS-401: http://www.sensorion-pharma.com/ima...RION_Corporate_Presentation_November_2017.pdf

 

Can this drug possibly prevent someone from T getting worse? Such a drug would be great, so we can do anything we want again?

 

A couple of poster presentations at the ARO Midwinter meetings on SENS-401: https://www.businesswire.com/news/h...ounces-Multiple-Poster-Presentations-ARO-2018