Otonomy OTO-413 — Treatment of Hidden Hearing Loss

Does anyone know if there was any discussion regarding whether higher or repeated dosing could have additional impacts?

 

That stood out to me as well. I think there is also just natural test variability, so the fact that they showed no improvement in the control group is very comforting that the results are meaningful.

 

We were born in the right generation:

 

Otonomy has stated that they tend to want to approach the FDA about possibly using a bigger dose in future trials.

 

More like born too early lol.

 

With these positive results will they get Fast Track status?

 

Seriously! Maybe born like 2 years too early though, lol.

 

Who knows. They could get Breakthrough Therapy and Fast Track status based off of these outcomes but that will be up to the FDA.

 

It's possible. Just like FX-322, there is no treatment on the market for hearing-in-noise deficiency.

 

Who knows if the powers that be at the FDA understand the significance of noise in speech understanding.

In my opinion it should meet the criteria.

 

I think it's notable that in their results presentation they highlighted the fact that it's (hearing loss in general) the 4th leading cause of disability globally and can lead to adverse health outcomes e.g. depression and dementia. It's also linked to a high economic burden so I think they could reasonably apply for Fast Track/Breakthrough Therapy status with those justifications for it. So even though it's a drug aimed at specifically at the 'hidden hearing loss' pathology, the arguments are still much the same as the ones Frequency Therapeutics have put forth for FX-322.

 

It should get Fast Track designation at the bare minimum.

 

Not to mention that the FDA has been instructed/more willing to grant Fast Track and Breakthrough Therapy statuses to medicines where it is applicable.

 

It’s so much harder to peg synaptopathy as a serious or life-threatening condition if left untreated, which is what the Fast Track is intended to primarily address.

OTO-413 does however meet an unmet medical need, it has a favorable safety profile, and one could argue that synaptopathy is an emerging public health issue under the ‘hearing loss’ umbrella.

For once, I might actually argue that OTO-413 proving improvements in tinnitus, and its co-morbidities, might help improve the case for the serious and life threatening part.

 

The FDA is out of touch, so much unnecessary suffering going on right now. I hope the Promising Pathways legislation passes in Congress next year so we don't have to put up with the sloth-like approval times.

 

The FDA isn’t the problem. It’s the legislation and executive branch that don’t make an effort to improve it. The most significant reform of the FDA took place from 97-99 under the Clinton admin. Obama built on it in 2012 with the FDASIA which gave us the Breakthrough Therapy designation. The last 8 years haven’t had much new.

 

Did they test for tinnitus in the recent clinical trial for OTO-413?

If they didn’t would they be testing tinnitus in the next phase?

 

They did not include tinnitus as an outcome measure for their OTO-413 trial. They could, like Frequency Therapeutics, get anecdotal feedback on tinnitus improvement if there was any. Your question seems like a good one to ask during the upcoming Otonomy Tinnitus Talk Podcast episode.

 

I hope someone out there who was in the clinical trial could let us know if they had any tinnitus improvements. We were quite lucky to get some positive anecdotes with FX-322.

 

Thank God they did not measure tinnitus in the current phase, so we can now spend months speculating if it works or not

 

I'm a bit confused about the 52% in the non-placebo group that had "adverse effects" from the trial. Since there seem to be no safety issue with the medicine itself, were these 52% all having troubles/pain with the injections/delivery method?

 

IT injections themselves have common side effects: transient dizziness, pain and headache, for example.

 

Alright. I just feel it might be to their advantage to clarify this in their report. Although, what they posted yesterday was not the full report, right?

 

I think the important thing to note here is that only 52% of patients experienced any adverse effects and for 76% of those patients the effects were "mild". I'm not a doctor or any have understanding of how they rate an adverse effect, but here's a quick "scale" I found on the interwebz:

• Mild Adverse Event – Event results in mild or transient discomfort, not requiring intervention or treatment; does not limit or interfere with daily activities (e.g., insomnia, mild headache).
• Moderate Adverse Event – Event is sufficiently discomforting so as to limit or interfere with daily activities; may require interventional treatment (e.g., fever requiring antipyretic medication).
• Severe and undesirable Adverse Event – Event results in significant symptoms that prevents normal daily activities; may require hospitalization or invasive intervention (e.g., anemia resulting in blood transfusion).

So with this in mind, it seems only 12% of patients (24% of 52%) experienced "moderate" adverse effects. I can't imagine a needle through the ear and the ET being filled with gel being the most comfortable feeling, even with local anaesthetic, so perhaps local "pain" would fall under a mild adverse effect, which is to be expected.

What doesn't make sense is that the presentation says there was a total of 29 patients in the cohort that received OTO-413 but "OTO-413 AE severity was mild 28/37", implying that more than 29 patients received the drug. I imagine they pooled in together both the treatment group and control group but somehow muddled the two together on the slide? Seems like a pretty big mistake to make so I must be missing something here, in which case what I said above further above can't be correct either.

 

OMG why does everyone here care so much about tinnitus? Just buy a fan and live with it (sarcasm).

 

The adverse effects rating is also somewhat subjective. Patient A might say the injection hurt and caused them to not be able to do anything the following day, while Patient B might have had some pain but continued as normal the following day. Therefore I think that there shouldn't be too much concern about the adverse effects of the medicine, especially when there was nothing glaringly adverse that would cause clear concern like multiple people being hospitalised for a prolonged period of time.

Is it also not possible that the 29/37 is referring to the whole cohort including the placebo group, as 29/37 would sound right for the whole trial population.

 

If I had to have temporary insomnia, mild headache, discomfort to get my synapses back... sign me up... sounds like living with hyperacusis already...

 

Right behind you on that. I have insomnia, trigeminal neuralgia and migraines all from hyperacusis.

A little ear discomfort is nothing.

 

I agree. Although a part of the clinical trials is assessing what happens with safety etc, I would have no problem taking a bit of pain to get a promising treatment such as this. The thing is though that this is no different to many types of surgery such as knee replacements, FESS nose surgery, foot surgery etc which come with pain. I'm pretty sure this is unlikely to be a reason to reject it.

 

I have wondered about the experience of having the IT injected gel and if that might qualify as an "adverse effect" for some people. I have had multiple IT injections over the past year and they are never fun, but they also aren't that bad. However, I have always gotten prednisone or dexamethasone which (mostly) drains out of the eustachian tube in 30 minutes or so.
I'd be first in line to get this done if I knew it was going to help restore my hearing, but I can imagine that having the area between your eardrum and round window filled with gel that sticks around for hours? days? is a somewhat disconcerting sensation and could "result in mild or transient discomfort."