After one late-stage flop, Auris Medical rejigs new PhIII for Keyzilen

Small cap Auris Medical ($EARS) says it will be moving the goalposts on its late-stage test for its tinnitus candidate Keyzilen (AM-101).

What’s prompted this change? Well, back in mid-August, the Swiss biotech said it had missed its co-primary endpoints in the key Phase III TACTT2 trial after Keyzilen failed to beat out a dummy therapy in treating patients with tinnitus.

Specifically, its med could not best placebo in creating statistically significant changes in tinnitus loudness and tinnitus burden. Cue its shares down by 65% on the news, decimating its market cap.

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Concerned by this failure, the biotech has said it will now change things around on another Phase III test for the med--the ongoing TACTT3 study--which is being undertaken in Europe.

It said it would be sending off a protocol amendment request to EU regulators around the use of the Tinnitus Functional Index (TFI) score--namely for it to be moved up from a key secondary endpoint to an alternate primary efficacy endpoint.

“Certain patient subgroups will be included in confirmatory statistical testing, and the trial size will be increased to enhance statistical sensitivity to the effects of treatment,” the company said in a statement.

This will have the effect of delaying the study’s readout, which were originally expected in Q4 2016, to “early 2018.”

TACTT3 had initially been set up as a randomized, double-blind, placebo-controlled test in acute and post-acute inner ear tinnitus, following traumatic cochlear injury or otitis media.

The trial had by August enrolled more than 300 patients during the acute tinnitus stage and around 330 patients during the post-acute tinnitus stage. The mark of its success was to be if it could produce a change in tinnitus loudness from baseline to day 84.

Under the amended trial protocol, however, it will be the change in tinnitus loudness and in the TFI from baseline to day 84 that become its new, alternate primary efficacy endpoints.

The biotech added that the outcomes from TACTT2 and the regulatory path forward “will be reviewed with the FDA in early December 2016.”

While TACTT2 failed to hit its marks, the trial data did show treatment effects on TFI in favor of Keyzilen for specific subgroups, and in the prespecified subgroup of patients suffering from tinnitus following otitis media, treatment with Keyzilen resulted in a “clinically meaningful and statistically significant reduction of 14.8 points in the TFI from baseline,” according to the biotech’s figures, as compared to 6.2 points for placebo--where a reduction of 13 points was defined as clinically meaningful.

A “trend for improvement” was also observed in active-treated patients who suffered from severe or extreme tinnitus at baseline with a clinically meaningful reduction in TFI of 15.5 points as compared to 11.5 points in the placebo group. Hence why the company is moving the goalposts in the hope of reproducing this elevated endpoint in the rejigged trial.

“Applying the Hochberg procedure, the two endpoints will be tested for the overall study population as well as for the subpopulations of patients with otitis media-related tinnitus or with severe tinnitus at baseline,” the company explained in a statement.

In order to “enhance the trial’s statistical power”, 60 additional patients will be recruited in TACTT3 in each of Stratum A and Stratum B; enrollment is set to resume early next year.

“Although we are disappointed that the TACTT2 trial failed to confirm the efficacy of Keyzilen in the overall study population, we feel very encouraged by the clinically meaningful reductions in tinnitus burden in two relevant subgroups,” commented Thomas Meyer, founder, chairman and CEO of Auris Medical.

“New knowledge gained from the TACTT2 trial allows us to make appropriate adjustments to the TACTT3 trial while we are still fully blinded to its outcomes. We believe that the measures outlined today will improve the probability of success of the TACTT3 trial for the entire study population as well as for key patient subgroups.”

The treatment contains esketamine hydrochloride, an N-Methyl-D-Aspartate (NMDA) receptor antagonist, made in the form of a biocompatible and biodegradable gel.

The news, which broke first thing this morning, was preempted by a nod that the company was set for an update, which was posted last night after normal trading hours. On this, its shares bounced 2.47% after ending the day down 1.22%, and was up nearly 4% premarket this morning. It had a market cap of just $55 million last night and was hovering close to penny-stock territory. 

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