Auris Medical Reports Key Results from Keyzilen® (AM-101) AMPACT2 Open-Label Extension Study

http://ir.aurismedical.com/phoenix.zhtml?c=253572&p=irol-newsArticle&ID=2263955

Auris Medical Reports Key Results from Keyzilen® AMPACT2 Open-Label Extension Study

• Trial outcomes show positive safety profile of Keyzilen® for chronic intermittent use
• Exploratory efficacy results support therapeutic concept of early tinnitus treatment

Zug, Switzerland, April 24, 2017 - Auris Medical Holding AG (NASDAQ: EARS), a clinical-stage company dedicated to developing therapeutics that address important unmet medical needs in otolaryngology, today announced key results from AMPACT2 (AM-101 in the Post-Acute Treatment of Peripheral Tinnitus 2), the open-label extension study of the Phase 3 TACTT3 clinical trial. The study confirms the long-term safety of Keyzilen® and further supports early treatment from onset of inner ear tinnitus.

"We are very pleased that AMPACT2 provides further evidence of good tolerance and safety for Keyzilen® and shows this, for the first time, also for chronic intermittent use," commented Thomas Meyer, Auris Medical's founder, Chairman and Chief Executive Officer. "In addition, the exploratory efficacy data from AMPACT2 lend further support to our therapeutic approach of treating tinnitus early, while the symptom is still of peripheral rather than central character." In 2015, an interim analysis of data from patients with post-acute tinnitus in TACTT3 provided first suggestions that improvements were more pronounced the earlier they had enrolled in the trial.

AMPACT2 is one of two open-label extension studies with Keyzilen® that were conducted at the request of the US Food and Drug Administration (FDA) to generate safety data from chronic intermittent use of Keyzilen® for up to 12 months. Participants who completed the TACTT3 trial were offered the option to roll over into AMPACT2, while still blinded to the treatment allocation. Patients were given the choice to receive up to three treatment cycles with each cycle comprising three intratympanic administrations of Keyzilen®, followed by a treatment-free observation period of 12 weeks. Of the approximately 660 patients enrolled in the TACTT3 trial up to June 2016, 485 patients rolled over into AMPACT2 and provided safety data; 422 of these patients provided exploratory efficacy data. At the time of enrollment into AMPACT2, all patients were in the post-acute stage; approximately half were from Stratum A (originally enrolled in TACTT3 during the acute stage; i.e. up to three months from onset) and the other half were from Stratum B (originally enrolled during the post-acute stage; i.e. between three and 12 months from onset).

The primary safety endpoint of AMPACT2 was the incidence of clinically relevant hearing deterioration five weeks after the start of a treatment cycle. In line with the results from previous trials with Keyzilen®, such incidence was low, amounting to 4-8% with no significant difference between one, two or three treatment cycles. During the course of AMPACT2, the patients' hearing threshold at the average of 4, 6 and 8 kHz was stable. The vast majority of adverse events that were considered related to the study drug or treatment procedure were rated as either mild or moderate in intensity. Seven patients experienced a total of eight non-fatal, serious adverse events, none of which was considered related to the study drug. Confirming previous data, 96-98% of tympanic membranes were already closed at the time of the first follow-up visit.

Exploratory efficacy analyses of AMPACT2 show improvements in the Tinnitus Functional Index (TFI) that were more pronounced for Stratum A patients compared to Stratum B patients. For Stratum A patients, the TFI decreased on average by 7.6 points (95% confidence interval 5.5 to 9.6; baseline of 40.3 points) to the last follow-up visit. For Stratum B patients, the TFI decreased on average by 3.5 points (1.4 to 5.6; baseline of 42.3 points) when enrolled in TACTT3 between three and six months from onset and by 2.5 points (-1.1 to 6.1; baseline of 45.3 points) when enrolled in TACTT3 between six and 12 months from onset.

Auris Medical expects to announce results from AMPACT1, the open-label extension study related to TACTT2, later this quarter. TACTT3 has been extended to recruit an additional 60 patients in each of Stratum A and B, and enrollment is ongoing; top-line results are expected in early 2018. As recruitment for AMPACT2 has completed, the open-label extension is not offered to patients currently enrolling in the extended TACTT3 trial.

 

Another press release that looks really good until you dig a bit:

1) 4 to 8% of people have a "clinically relevant hearing deterioration"

2) the best case scenario was an average reduction of 7.6 points with a 95% confidence interval of 5.5 to 9.6 points on the TFI. Unfortunately, the minimum reduction considered "clinically meaningful" to patients is around 13 (http://www.audiology.org/sites/default/files/publications/tinnitusFunctionalIndex.pdf) though of course some people might find a 9 or 10 point reduction meaningful.

And this is of course not placebo controlled.

 

AM-101 is done and dusted I feel. Forget it and go live your life and put your faith into regenerative medicine which is probably 20 years away before some of it hits the market. It sucks yes, but there's not really much else we can do.

 

We don't know what the future holds. None of us thought we would get tinnitus or hearing loss. I just want a dang device to help with this tinnitus.

 

Does anyone know if Auris Medical (Altamira Therapeutics) is still studying Keyzilen (AM-101)? Phase 3 failed?

 

They had two Phase 3 failures - TACTT2 and TACTT3.

As of 2019 they still believed in the drug, however, they'd already burned through all of their funding. It's still listed on their website, so maybe at some point they'll revisit it? Years ago I read that gacyclidine (OTO-313) was a much stronger NMDA receptor antagonist (I think on this forum actually). I don't have a source for that though. I imagine AM-101 is basically dead in the water at the moment - though that could change.

If OTO-313 fails, it probably means NMDA receptor antagonists don't work. If OTO-313 does work, I wouldn't be surprised if Auris Medical tries to scrap together some funding for one last Phase 3 to try and beat OTO-313 to market (or at least get there shortly afterward). Though then again, they don't have a slow release gel like Otonomy, and that may have been something that hurt them (instead their study involved getting multiple injections).

 

Thank you for your feedback.

Indeed, everyone hopes that OTO-313 will be effective as an antagonist against NMDA receptors.

There was this study here that informed that no known drugs on the market were very favourable for NMDA antagonists:

The Management and Outcomes of Pharmacological Treatments for Tinnitus

 

What NMDA antagonist did Auris Medical use in their treatment?

 

I skimmed the paper, though didn't see anything about NMDA anagonists. It mentions the Sertraline study. I tried that but couldn't make it past day 3. It caused horrible side effects and made my tinnitus to go through the roof (I could hear it in the shower). It also mentions a surgical study regarding cutting the auditory nerve (side note: this is from the paper it quotes):

That is a little concerning, and does give some credibility to the idea that tinnitus either moves to the brain after a while or exists in the brain for some people. Or it could be that there are simply different kinds of tinnitus.

Esketamine hydrochloride. Interestingly, OTO-313 (gacyclidine) is closely related to PCP (the street drug also known as "angle dust"). I don't know enough about chemistry to know how close it is or if its closeness means anything.