Otonomy OTO-413 — Treatment of Hidden Hearing Loss

This is so disappointing. I understand that ultimately their goal is to put together a product that works no matter how long it takes, regardless of how much the "little people" online currently suffer. But this just tacks on more time to the suffering. Not what I wanted to see at all.

 

Otividex Phase 3 initially failed because vertigo episodes in Meniere's are highly subject to the placebo effect and their placebo group saw great gains (because their previous Phase 2 results were so good). They had to restart the trial using different recruiting and a different statistical analysis. We don't see any of that here because the placebo group for OTO-413 didn't improve.

They had multiple speech-in-noise tests for OTO-413 and reading between the lines results were better for certain tests than others. This might be tangentially related to Frequency Therapeutics in that Frequency Therapeutics believes some aspects of speech-in-noise hearing are related to very high frequency hearing per their presentations (and the Tinnitus Talk Podcast). They might get even better results focusing on the tests that highlight the synapse component better (whatever that would be).

It's also possible they just want to reformulate with a higher dose and would rather do an additional Phase 1 so that formulation is the one that goes to market.

Pipeline Therapeutics is also working on synapses, not just Hough Ear Institute btw.

 

What competition? None of these drugs yet exist in the market.

I honestly don't think speculative potential competition years down the line concerns them as much as the challenge of getting their own drugs out the door.

By "refining study protocol" perhaps they realized they needed to tweak the endpoints to increase their chances of FDA approval.

 

The annoying thing is all three are now roughly on the same timeline. If Hough Ear Institute starts their Phase 2 this year, they actually might be ahead...

 

You're absolutely right. I'm sure they don't care about competition as long as the drug works and works well. It will sell itself if it does.

 

In this case, how come Frequency Therapeutics was allowed to increase the dose of FX-322 in Phase 2a?

 

Frequency Therapeutics didn't have to reformulate their whole drug. Otonomy is using an extended release gel, so to change dose (if they wanted to), they would have to reformulate.

 

Bad drug research news.
Why am I not surprised?

 

What do you guys think is the most promising; Otonomy, Hough Ear Institute, or Frequency Therapeutics?

 

Frequency Therapeutics hands down.

 

Frequency Therapeutics only has 2 projects in development, unlike Otonomy. But Frequency Therapeutics are further ahead than anyone else when in comes to clinical trials.

 

Technically, if you count Otovidex for Meniere's, Otonomy is further ahead (and they have a swimmer's ear drug already on the market) since it would be released this year on good Phase 3 data. But definitely Frequency Therapeutics is moving very fast. Very well run company.

 

You're absolutely right, I was talking about the hearing loss drug. I should have mentioned that.

I read that you own Frequency Therapeutics stock, did you also buy shares of Otonomy?

 

Nah, I don't have enough money to invest and diversify more. I would if I did.

 

Very annoying news that Otonomy will take even longer now...

 

I'm beginning to see why veteran members are so jaded about regenerative meds.

 

I'd rather Otonomy does a good job and develop the best drug possible, than give me some half baked drug that might do half the job.

I'm suffering just like everyone else, but at least this isn't 30 years ago when none of these companies or drugs were even an idea yet.

At least today we have multiple companies, people, institutional money, scientists, doctors, academics, and money hungry capitalists working in our favor.

Keep it together people. Good news is on the horizon...

 

You're right but tomorrow isn't guaranteed and suffering everyday with no joy or purpose to life is stupid.

 

Forgive me, but why single out veterans? Why wouldn't any sensible person not be jaded about regenerative meds? It's 2021. How many years have scientists been working on the eradication of tinnitus? Still no cure. So of course a sensible person doesn't believe. But... humans may learn to fly and alter the genome to regress aging. Hope springs eternal... lol.

I will say on a more serious note, that I am very surprised, with all the time and energy dedicated to the elimination of tinnitus, that the riddle has not been solved. What a difficult assignment it has been proven to be. The concept of sound... a construct of the mind... that can't be dissected to eliminate unwanted noise from the sound we want to perceive based upon change in air pressure. The most difficult of tasks apparently.

 

To be fair, if you read tinnitus research papers from the 80s and 90s it’s interesting to see quite a few of them say one of the main causes of tinnitus is cochlear damage (i.e. hearing loss), and then in the next sentence go on to describe how unfortunate it is that there is no way to regenerate hair cells - synaptic damage was still flying under the radar at the time outside of Liberman - and that subsequently, tinnitus treatments would likely need to target the brain unless regeneration becomes feasible.

So one could argue that all these years spent trying to regenerate hair cells, has by proxy, also been an attempt at treating cochlear tinnitus itself.

 

Regenerative meds for the ear/cochlea have never been designed with the intention of treating tinnitus. They've always been designed with the intention of restoring hearing first, anything else is a bonus. The same goes for FX-322.

As for eradicating tinnitus, the truth is that this is an area of research that has never received enough attention or funding, mainly due to the fact that Jastreboff's TRT became dogma and was wrongly accepted as an adequate "treatment". The result? 30 years of underfunding and minimal research into treating tinnitus. All that man has ever done is prolong our suffering. As if that wasn't bad enough, he extended his dogma to hyperacusis patients as well.

So here we all are, on an internet forum, frothing at the mouth for whatever regenerative drug may come out that could help those of us with tinnitus/hyperacusis as a 'by-product' of treating hearing loss. And indeed this kind of research hasn't been going for that long in the grand scheme of things, especially when you consider that it takes a drug 10 years to get to market. However, 10 years is a substantial chunk of someone's life. I'm only on this forum because of my hyperacusis, not my tinnitus, but I know for a fact that if I'm still on this forum in 10 years from now with none of the current drugs in the pipeline having worked (FX-322, OTO-413), I too am going to feel a little jaded, to put it mildly.

 

I just realized this, but the strange spiral design around the O in Otonomy's logo is meant to represent a cochlea. I think that's a nice little touch. I'm not sure how I missed that.

 

A bit of unfortunate news from Otonomy today, their Ménière’s drug, Otividex, has failed its second phase 3 trial. This drug was important to the company because it was expected to help generate cash revenue to help the company fund the other studies in its pipeline. However, they seemed optimistic in their news release today that they had enough cash on hand to get them through the clinical study readouts of OTO-313 and OTO-413 next year:

“Our focus turns to the strong pipeline we have built as recently highlighted by the successful clinical trial results for OTO-313 in tinnitus and OTO-413 in hearing loss. OTO-313 and OTO-413 each address a large patient population with significant unmet need and no approved drug therapy. These programs provide an attractive opportunity for the company with clinical readouts anticipated in mid-2022. We expect that our existing cash balance will permit us to achieve these clinical readouts as well as advance our preclinical hearing loss programs including OTO-825, a gene therapy for congenital hearing loss."

The company previously reported a cash balance including cash, cash equivalents, and short-term investments totaling $86.3 million as of December 31, 2020, GAAP operating expenses for full year 2020 of $42.6 million and non-GAAP operating expenses, which exclude stock-based compensation, for full year 2020 of $36.5 million.​

 

Bad news turns to worse. Otonomy's Meniere's drug has failed Phase 3 (again).

Otonomy stock loses half its value after disappointing trial results of vertigo treatment

Otonomy re-running Phase 1 for OTO-413 is now starting to make a bit more sense for several reasons. Had Otividex had positive results, it's likely that Otonomy would have been able to improve their cashflow situation (they currently have enough for 2 more years of operations). The problem is, their current cashflow situation is not enough to get them to Phase 3 for both OTO-413 and OTO-313. So they now know that in the absence of generating their own profits, they have two years to turn things around, unless they're able to get more investors on board. Given they've already had their hands burnt (twice) with the same drug, I think their credibility will most likely be damaged. I can't imagine what Otonomy must be saying now to the investors who financed the running of Phase III for Otividex again.

So, in order to survive as a company, they will at some point have to get more investment on board. The only way that is now going to happen is if they have killer results from their Phase 2 clinical trials, and I imagine they already think that's more likely to happen with OTO-413 than OTO-313.

With this in mind, Otonomy reformulating at Phase 1 makes sense for two reasons:

a) It is cheaper and more sensible to reformulate at Phase 1 than play around with reformulation at Phase 2 at the expense of reducing your population groups.
b) If they can find the optimum dose at Phase 1, their Phase 2 results are more likely to knock things out of the park and get more investors on board.

You gotta feel for Otonomy's CEO. The guy has Meniere's himself.

 

Otonomy did not mean it's endpoints for Meniere's vertigo attacks:

Otonomy Announces Top-Line Results for the Phase 3 Clinical Trial of OTIVIDEX® in Patients with Ménière's Disease

This really surprises me. Intratympanic steroids are part of routine care for Meniere's vertigo so shouldn't any version fare better than placebo? And i would think a long acting extended release version should show even more benefit.

I wonder they ever done a placebo controlled trial with IT steroids and Meniere's attacks in general. Maybe they do not show benefit beyond the placebo effect and shouldn't be part of the standard of care for vertigo attacks.

 

That's a darn shame, I feel bad for Meniere's patients. Hopefully the results from Frequency Therapeutics will be better.

 

This is not a good look for Otonomy. First the OTO-413 trial delay and now this; my excitement for them is starting to waiver. Sure am glad I didn't invest in their stock.

Seems like FX-322 is the last man standing for now, and we'll find out once and for all how well the drug works in March. If results for that aren't good then I don't even know...

 

Agree. Vertigo attacks are a nightmare. They need a good therapy for refractory ones.

 

It's such a shame that it essentially all comes down to money. Research for life changing treatments gets held up while some people have more money than they know what to do with. I fully understand that it's just the reality of it all, but when you think about it it's kind of surreal that promising companies have concerns about funding.

 

Well, let's hope Otonomy can fund everything else in their pipeline or find another willing investor.