Otonomy OTO-413 — Treatment of Hidden Hearing Loss

Nothing to worry about. Tax-related.

 

That's assuming it isn't excitation of the nerve fiber, which comprises a nontrivial subset of tinnitus cases (e.g., inflammation, hydrops) and it's a way easier problem to fix. I have some cautious optimism about OTO-313 and I don't believe most cases of tinnitus are a matter of centralization. Remember this, brain scans are correlates and nothing else. Doesn't matter if it's EEG, fMRI, fNIRS etc. Don't get me wrong, I believe certain etiologies are a matter of centralization, but technically they can't prove it without ablation of the fiber.

 

Dang. I can't help it, I'm getting as excited for the results as I was last year for FX-322.

 

That's a good thing. Hope is important for finding a treatment or cure.

 

When does "early" Q2 become "mid"?

Asking for a friend...

 

Early Q2 can be until end of April, so it's still early Q2.

 

Mid-May is my hope at the latest for any information worth reading.

 

I was so happy to read about the positive results. Then I woke up.

 

Otonomy Reports Positive Top-Line Results from Phase 2a Clinical Trial of OTO-413 in Patients with Hearing Loss

Not outstanding but not bad. The 5x dose will be interesting.

 

• 40% (8 of 20) OTO-413 subjects demonstrated a clinically-meaningful improvement on at least one of the three SIN tests at both Days 57 and 85 versus 20% (2 out of 10) for placebo.
  
  
• 15% (3 of 20) OTO-413 subjects demonstrated a clinically-meaningful improvement by two or more different SIN tests at both Days 57 and 85 versus 0% (0 of 10) for placebo.
  
  
• For the Words-in-Noise test that has been well-established and validated in hearing loss patients, 40% (6 of 15 with evaluable tests) OTO-413 subjects demonstrated a clinically-meaningful improvement at both Days 57 and 85 versus 0% (0 of 9 with evaluable tests) for placebo.
  
  
• Most of the patients enrolled in this trial also had moderate-to-severe high-frequency hearing loss measured with standard audiometric testing. The responder rate for OTO-413 was favorable in this subset as well with 41% (7 of 17) OTO-413 subjects demonstrating a clinically-meaningful improvement in at least one SIN test at both Days 57 and 85 compared to 13% (1 of 8) placebo subjects.
  
  
• The PGIC demonstrated a treatment benefit with 50% (10 of 20) OTO-413 subjects reporting an improvement from baseline at both Days 57 and 85 compared to only 10% (1 of 10) for placebo.
  
  
• Treatment with OTO-413 was well tolerated. There were no serious adverse events and no discontinued patients due to an adverse event (AE). 32% of OTO-413 and 46% of placebo subjects reported an AE, most of which were mild.

Based on these positive results, Otonomy intends to initiate a full dose-ranging Phase 2 trial in hearing loss patients by the end of 2022. This trial will also incorporate learnings from the ongoing higher dose evaluations that are assessing the tolerability and treatment activity of two higher doses of OTO-413: 0.75 mg and 1.50 mg, which is five times the dose evaluated in the Phase 2a trial. Results from the higher dose evaluation are expected in the second half of 2022.

 

YEAAAAAAAAH. Next up: OTO-313

 

Again specific subgroups that benefit and some that don't.

11/20 in total with clinically measured improvement is not that spectacular indeed.

 

I wasn't expecting magic solution, so these are good results, to regain back good hearing, it will be more like multiple different treatments to stimulate different things.

 

Fantastic news!

 

Don't expect miracles from first generation hearing loss therapies.

 

For any illness or disorder, there will always be heterogeneities in what's causing it.

 

Indeed and remember: even a subset of hearing loss sufferers translates to millions of people that can be helped worldwide!

 

IT'S WORKING, PEOPLE!

ALL ABOARD THE HYPE TRAIN!

CHOOO CHOOOO.

 

This larger, extended Phase 1 trial (at some point renamed a Phase 2a trial) was just to confirm that the drug works, and from this data it looks like it does. I was starting to get worried but this data - while not as good as the original set - is still good and it bodes well for the 5x dosage trial that's going on right now. I've long felt Otonomy has underdosed their drugs (it's one of the reasons I think Otividex failed - a drug that really should have worked), so the 5x trial should show us what this drug can really do.

I found this exciting (PGIC = Patients' Global Impression of Change):

Assuming the 40% who saw an improvement on a test are a subgroup of that group, it means people are really noticing a real world effect from the drug.

 

Great news y'all!

Very excited for higher dose results!

 

What if FX-345 shows improvements of at least 20 dB in audiograms?

 

Thank you my God and thank you Otonomy. Keep up the good work.

 

I was wondering why investors don't seem to care about the results. So I compared them with the Phase 1/2 results and this does curb my enthusiasm a bit.

40% vs 67% OTO-413 subjects demonstrated a clinically-meaningful improvement on at least one of the three SIN tests at both Days 57 and 85.

15% vs 33% OTO-413 subjects demonstrated a clinically-meaningful improvement by two or more different SIN tests at both Days 57 and 85.

Still clearly better than the placebo group though.

 

Absolutely, but OTO-413 was one of the treatments with most potential. A 40% success rate is great obviously but I guess I was hoping for more. Intratympanic injections caused worsening for some people - I'm not too keen on a 40/60 treatment with possible adverse affects on the tinnitus.

Too bad there are no anecdotes provided on tinnitus. You'd expect at least some of them have tinnitus.

Either way let's stay positive, assuming that the high dose will push this well over 50%!

 

Perhaps there are very subtle differences between the groups of hearing loss. For example hearing loss from a shotgun blast of 180 dB might have different kind of damage compared to a decade of being a musician. This may explain why some respond and others don't. Different kinds of damage.

Either way, it looks like we have something that works for at least a subset of the population.

 

Yep, it seems to have caused some confusion among investors. People expected the results to be more in-line with the previous ones, yet they weren't bad and still showed the drug still worked over a larger sample size. I also think the placebo effect showing its head has spooked some people a little. It seems like a 10-20% response rate for placebo patients is going to be normal for hearing studies (which is what we've seen in the FX-322 trials). However, I think the two time point threshold they've setup is protecting them somewhat. In the previous trial they also had placebo responders, but they only responded at one time point:



This time 2 of 10 placebo patients responded, but only 1 of them reported a positive PGIC, which means they scored higher twice, but didn't believe they got any real improvement from the drug (so maybe their initial test was just low).

I don't think they reported the PGIC score last time, but the fact that it's 50% for the OTO-413 group is really good. It means patients feel the drug working.

 

I suspect these higher dose trials are going to have very good results for both Otonomy and Frequency Therapeutics based on how their original formulations performed. Now that we know they're generally safe, it's time to maximize their effect!

 

Agree! Still a long way to go and investors know that.

Might be a slow uptick during the next days if the markets are in green.

 

Stock is up by 11% so investors are happy as they see potential here. If they are happy, we should be too!

 

Based on the heterogeneity of hearing loss, 40% to 50% of subjects improving is spectacular considering improving hearing has never been done before and not everyone that has hearing loss is guaranteed to have synaptic damage that can benefit from OTO-413.