Otonomy OTO-413 — Treatment of Hidden Hearing Loss

I went down a bit of a rabbit hole and am now warmer on that idea, though I still think it's best to keep tinnitus out of the trial. If they wanted to check for that it would make more sense to do a separate Phase 1/2 study that focused just on that. If the trials aren't focused there will be problems like what was seen in the FX-322 Phase 2a trial.

 

Sorry, I forgot to quote that part of your last post, but I meant to say I absolutely agree with you on that! At the end of the day we all want the trial to succeed, and I share your sentiment that keeping tinnitus out of it gives them the best shot.

(I'm still puzzled over them excluding musicians from the trial though...)

 

IIRC, musicians, even those who use hearing protection, tend to have tinnitus simply due to their regular exposure to loud music. So it's probable they just wrote them off as a whole to avoid any problems.

 

Yeah, reading over the inclusion/exclusion criteria again, I think you're right. Maybe this is another layer of protection against people lying about their tinnitus to enter the trial. Now that I think about it, musicians are uniquely positioned as a profession that 1) is constantly exposed to loud sounds and 2) almost never wears hearing protection. In other professions, hearing protection is taken much more seriously, especially in an industrial setting. Obviously not every musician has tinnitus, but it's probably easier and less risky to not let any musicians in altogether.

 

Well, they should have excluded more professions if they wanted to be really precise to who they enroll, as there are industries way more noisy (construction, waiters in clubs etc etc) and we kinda know that earmuffs, earplugs etc don't give the protection they advertise.

The reality is that a huge chunk of musicians nowadays do their stuff from their home studio or so (music producers selling music, content creation, YouTube/TikTok, selling merch etc), minimising their noise exposure to maybe less than other jobs.

Having said that, they could maybe have noise exposure as performers, but at least professional ones use in ear monitors which serve as hearing protection too. The other employees in live music places rarely wear any protection, let alone the audience...

Just adding my note as a musician that feels a bit offended by that exclusion criteria lol.

 

One of the things that is sometimes recommended to maximise your speech understanding is to learn a musical instrument. Otonomy might feel that including musicians might skew the results in some way- bearing in mind that speech understanding is the primary measure. Perhaps musicians might benefit less because they are already using their hearing closer to its full potential.

 

So just bumping up this thread to summarise where we are.

I believe this is a repeat of Phase 1/2 currently in trial and expected to end soon with a higher dosage used this time? Results end of this year?

 

They're running two mini-trials of 12 people each (8 get the drug, 4 get placebo). One is using 2.5 times the dose of OTO-413, and the other is using 5 times the dose of OTO-413 (compared to the Phase 2a trial).



On March 1st of this year I emailed them about these trials (before the 5x dosing was announced), and they responded:

At some point later (not sure), they announced the 5x dosing. So that must mean the 2.5x dosing was deemed safe. It's unclear to me if they know the results from the 2.5x trial. In addition to higher dosing, they're also considering giving a second shot (this was discussed prior to the two high dose trials). They're most likely looking for ways to boost the efficacy signal.

 

Minor update: According to their latest press release, the two OTO-413 high dose studies ended up with 19 patients each: "Each higher dose cohort completed enrollment of 19 hearing loss patients randomized 2:1 to OTO-413 or placebo, with top-line results expected in the fourth quarter of 2022."

I suppose this is good news as it'll give them more data to work with. It's strange that we haven't heard anything from anyone in the previous studies. I'm curious how big a benefit people are experiencing.

 

Is it possible there's an NDA or similar agreement preventing people from discussing their experience(s)?

 

To add: the results of these higher dosage studies will be out this quarter.

 

I listened to their earnings call, nothing to report. No video feed in this one (sometimes they have video). I didn't get any weird vibes, though I didn't get any vibes indicating they know what's coming either, so it seems like management doesn't know anything yet.

Possibility, though the OTO-413 Phase 1/2 or Phase 2a studies are done with and the data is out. I would assume people in those studies could talk about it, though then again, I don't know what the rules are.

 

I can't find the two mini-trials on clinicaltrials.gov, do you know if they are listed?

 

I don't. I've searched before and come up empty handed. Otonomy did say the mini trials were exactly the same except for the higher dose. I'm not sure if they're not required to list them because the trial is so small, or if they can do the trial under their existing one. Their current clinical trial page is clearly their Phase 1/2 and Phase 2a trials combined (side note: Otonomy originally referred to "Phase 2a" as an extended Phase 1/2 - I'm guessing they changed the verbiage to better separate out the data).

 

It may be pre-mature, but given the more objective measurement methods this drug is going to be tested with, as well as the previous results, we have a good reason for optimism.

The earliest we can expect results from this trial is going to be October 2022 and possibly later into December 2022.

 

I've learned from the OTO-313 trial not to be optimistic.

Optimism for me would be a successful Phase 2 trial that showed at least moderate results (not slight) for a realistic chance of it passing Phase 3.

 

OTO-313 was tested in a more subjective way. Which probably allowed for more subject influence. OTO-413 uses word in sound testing which is more objective. It can still crash and burn but unlikely due to the placebo effect.

 

Didn't we accuse the FX-322 participants of lying in the WIN tests to get into the trial?

 

Frequency Therapeutics released evidence of suppressed word recognition scores used by patients to gain acceptance into the FX-322 Phase 2A. Which resulted in really abnormal measurements in the placebo group (and drug group). They remedied that with an elongated lead-in period with additional testing gates; which in practice, reduces the likelihood of a patient faking their way into the test. Otonomy already has a similar lead-in for OTO-413. It doesn't sound as controlled as FX-322 Phase 2B, but should reduce unexpected variability with the placebo group.

Also, the battery of noise-recognition tests used in the OTO-413 trial alone are much more challenging and sensitive than what is used for FX-322 anyway.

 

After one failure after another, I think it's safe to believe that neither OTO-413 nor any of their other products looks that promising anymore...

 

I understand how you can feel like that but it makes no logical sense. Other treatments are completely different to previous ones that have failed.

 

Just got an alert email from Otonomy (I'm signed up on their website), they're laying off 55% of their staff to focus on OTO-413:

Definitely a bit sad and not terribly encouraging, but I suppose this is a necessary step given their current condition.

 

Hopefully their focus on OTO-413 will yield better results.

 

I do think Otonomy were genuinely shocked at OTO-313's Phase 2 results. I wonder how high the placebo actually was? People exaggerating their TFI scores to get into the study, then, once in, giving real scores? Who knows.

Yes, let's hope OTO-413 has good Phase 2 results.

 

I hope they have enough cash now. Very bad timing with how the Fed is going through a tightening cycle right now too. They are burning cash way too quickly.

 

Fed rate hikes have little to do with their cash on hand. Inflation will cause them to burn more quickly in the short term. And frankly, there is no long term for Otonomy if their trials don't succeed.

 

In that department OTO-413 has a chance, but without its success Otonomy is likely sunk.

 

Hopefully the next results are good. They need some good signals quick.

If OTO-413 is a success, then it will open up funding for the other ones too.

The other drugs they are planning sound interesting but that would be a very long time to market if they even ever do.

 

Only highly significant Phase 2 results for OTO-413, published on time, will save Otonomy. Once burned, investors will take a lot to return.

 

This is what's so maddening to me, given we just saw this happen with FX-322. I guess it was maybe too late as Otonomy had already begun their trial design but I can't help but feel like they shot themselves in the foot if the placebo group is actually what brought them down. (Perhaps it wasn't - someone please correct me).

What evidence do we have that the same trial issues from FX-322 and OTO-313 will not occur with OTO-413?