Otonomy Otividex Fails in Phase 3 Ménière's Trial

Bad news from Otonomy. Their Phase 3 trial for Otividex failed in a Phase 3 trial. Statistically, this wasn't even close with p-values in the .8 to .9 range. Additionally, they are reviewing the entire product pipeline so who knows what the effects might be for OTO-311 or their OTO-4XX candidate.

Here's the press release (http://investors.otonomy.com/phoenix.zhtml?c=234082&p=irol-newsArticle_Print&ID=2297312):

Otonomy Reports Results for AVERTS-1 Phase 3 Trial for OTIVIDEX™ in Patients with Ménière's Disease

• Missed primary endpoint (p value = 0.62) and all key vertigo secondary endpoints
  
• Company to immediately suspend all development activities for OTIVIDEX
• Company is also undertaking a review of its product pipeline plans and commercial efforts in order to identify opportunities to extend its cash runway and build shareholder value
• Management will conduct a webcast and conference call to discuss the results at 8:00 a.m. EDT today

SAN DIEGO, Aug. 30, 2017 (GLOBE NEWSWIRE) -- Otonomy, Inc. (NASDAQ:OTIC), a biopharmaceutical company focused on the development and commercialization of innovative therapeutics for diseases and disorders of the ear, today announced results for its AVERTS-1 Phase 3 clinical trial of OTIVIDEX in patients with Ménière’s disease. The AVERTS-1 trial was a 16-week, prospective, randomized, double-blind, placebo-controlled trial that enrolled a total of 165 patients with unilateral Ménière’s disease in the United States. The clinical trial missed its primary endpoint which was the count of definitive vertigo days by Poisson Regression analysis (p=0.62). Patients in both the OTIVIDEX and placebo groups showed similar reductions in the number and severity of vertigo episodes during the three month observation period. OTIVIDEX patients reported a 58% reduction from baseline in vertigo frequency in Month 3 vs. 55% for placebo patients.

As summarized below, the trial also failed to achieve statistical significance (p < 0.05) for any of the key secondary vertigo endpoints at Month 3.

Vertigo Endpoint at Month 3 p value
Change in Vertigo Frequency from Baseline 0.99
Mean Vertigo Severity Score 0.93
Average Daily Vertigo Count 0.81
Results for Month 2 were similar. Daily diary compliance, patient drop-out, patient demographics, and baseline vertigo characteristics were similar between groups and consistent with expectations based on the Phase 2b trial.

“We are greatly disappointed by these results, and surprised by both the higher placebo response and lower OTIVIDEX improvement than observed in our previous trials. I would like to thank the many patients and investigators who participated in our Ménière’s clinical program," said David A. Weber, Ph.D., president and CEO of Otonomy. “Based on these results, we are immediately suspending all development activities for OTIVIDEX including the ongoing AVERTS-2 trial. In addition, the company is undertaking a review of its product pipeline and commercial efforts to identify opportunities to extend its cash runway and build shareholder value."

As of June 30, 2017, the company held cash, cash equivalents, and short-term investments totaling $150.5 million with prior non-GAAP operating expense guidance of $80-85 million for 2017. The company is withdrawing the spending guidance for the year pending the above-mentioned review.

 

Shares are down 83%.

I don't see it impacting their other product candidates though, they do have plenty of cash & cash equivalents to continue their operations. As described in an article this product is not comparable at all to the ones we are interested in:

Source: http://www.xconomy.com/san-diego/20...-loss-drug-after-phase-3-flop-shares-routed/#

 

I wonder if they're still going to do a Q&A with Tinnitus Talk regarding OTO-311, probably not.

 

Later on today?

 

As it's for acute tinnitus I don't think it will interest us anyway, I think the only hope we have for chronics are "brain" drugs... in many years to come or DBS.

 

Realistically, you mean?

What is the difference between acute and chronic tinnitus?

 

Acute is sudden tinnitus, so if we can treat tinnitus before it comes established in the brain. Such as soon after an acoustic trauma. The window for opportunity is still yet to be tested. I.e blocking NMDA receptors to stop the effects of a glutamate storm.

Chronic is when the neurological pathways in the brain have already been altered and recent research has shown that chronic tinnitus originates in the brain.

According to the Auris Medical's website, it is unlikely a cure for chronic tinnitus will come in the near future.

I don't see Auris Medical or Otonomy having offered any explanation to how they could help chronic sufferers.

 

Knowing a bit more about OTO-4XX and the synapses regeneration would be awesome as well.

 

So acute tinnitus is not in the brain?

 

Just don't get your hopes up any regeneration if possible is going to free you from tinnitus, until a scientific explanation to how it may comes up. Theorising it will reverse natural plasticity is not a scientific explanation.

 

Are you going to repeat this every day?

 

If you prefer to believe Auris Medical, the same company that has achieved absolutely nothing so far and keeps trialing the Keyzilen bullshit, and their "there won't be any cure for "chronic tinnitus" (whatever this is)" claim, then go for it. But, please, stop spreading your depression, negativity and shit talking every thread you go.

 

I want somebody to challenge me, believe me I hope I am incorrect. But after a while of having tinnitus the hope for a cure dies and you see more an objective view of tinnitus and why it is so difficult to treat.

From what I read, it starts in the ear to establish itself in the brain. That's why the effects of ear injuries last far well beyond the injury, a bit like phantom pain.

 

Auris medical have a team of scientists working on their products everyday, it would be logical to listen to them surely. A professor in tinnitus research also has the same opinion as me, I don't want to depress anybody, I just want a debate with scientific knowledge and fact and what has already been documented in papers. False hope gives no winners unfortunately.

 

But how can you hear acute tinnitus if it's not via the brain?
Does the tinnitus go out of your ears again when acute?

 

On the other hand I just read on reddit tinnitus that scientists will crack seeing tinnitus objectively

That to me sounds like progress

See the tinnitus... or the brain on tinnitus... find a way to manipulate what is causing it...

Don't get down or upset by this news that just means that particular method doesn't work and we can learn from it right

 

That's a bit like asking why do some people experience temporary tinnitus and permanent tinnitus. Excellent question. I wish I knew the answer.

 

Why would we? This drug wasn't even for tinnitus...

 

Let's be real we all hoped it would help or yield results for tinnitus since we're all suffering. You are right though.

 

This is the break scammers have been waiting for, another product failure another opportunity to sell to desperate people...

I think tinnitus would be much harder to treat than vertigo/Meniere's, it's a massive set back I wouldn't underestimate it.

 

Well, I didn't. I can't see why curing Ménière would cure tinnitus, too. Tinnitus wasn't even an outcome of any of the four Otividex's trials. Actually, it looks like the drug was only aimed to reduce the number of days with vertigo attacks. Nothing more.

 

It's a massive setback for the company anyway. Investors' confidence will fall for one in any of the other product candidates.

 

Good and fair point.

 

Another disappointing news...
I don't think it will not affect OTO-311 at least in terms of monetary conditions... financial issues, motivation of the employees, 80% share crush and so on... we have to wait so many years...

 

I try to never be too optomistic but I don't think this failing is the worst thing for tinnitus sufferers. It was more for vertigo, and had more to do with the ears, not brain. This just more proves tinnitus is a brain issue, which we could now focus on that. I still feel really bad for people with menieres

 

If your tinnitus is caused by damaged nerves or ihc/ohc, and these would be restored, and the brain would be picking up signals again, why wouldn't it disappear.

Like with alcohol, if you're addicted, and you get none, you quiver. Over time, this effect will decrease and you'll stop quivering. I believe, similair will happen after hearing restauration. The old normal will be picked up and tinnitus will fade.

 

Here is a link that focuses on NMDA receptors that Otonomy are focusing on to treating tinnitus. It may shine some light to why it might work

http://onlinelibrary.wiley.com/stor...16&s=19fdf103dc3d93568c6ce97b805d1880f783ecae

 

I hope so, but it doesn't explain why some of those with a loss and corrected with a hearing aid don't see any change in tinnitus, or when the audiotory nerve is cut - sometimes it fixes it sometimes it doesn't, there are so many unanswered questions we cannot assume it will work. That's why it's important other avenues for fixing tinnitus are addressed and supported.