Auris Medical acknowledged today that its acute inner ear (sensorineural) hearing loss candidate AM-111 has failed a Phase III trial, a setback that has prompted the company to terminate a second late-stage trial.
AM-111 missed its primary endpoint in the Phase III HEALOS trial (NCT02561091) of statistically significant improvement in hearing from baseline to day 28 compared to placebo. Patients treated with 0.8 mg/mL of AM-111 showed a mean hearing improvement of 36.6 dB compared with 33.4 dB for placebo patients. Patients treated with 0.4 mg/mL of AM-111 showed a better average improvement of 38.4 dB.
However, Auris Medical quickly added that the drug did show a statistically and clinically significant effect on day 28 following treatment in a subpopulation of patients with profound acute hearing loss, defined as a mean hearing threshold of 90 dB or higher.
Patients in the subpopulation who received 0.4 mg/mL of AM-111 showed improvement at day 28 of 42.7 dB, compared with 37.3 dB for 0.8 mg/mL patients taking AM-111, and 26.8 dB among placebo-treated patients.
“Although the trial did not meet our expectations on the primary efficacy endpoint in the overall study population, we are very pleased to see the statistically and clinically significant treatment effects in the profound hearing loss subpopulation,” Thomas Meyer, Ph.D., Auris Medical's founder, chairman and CEO, said in a statement.
“Considering the high unmet medical need, we look forward to discussing the regulatory pathway for AM-111 with the regulatory agencies.”
Investors, however, apparently did not share Meyer’s optimism, reacting to the Phase III readout results with a stock selloff that sent shares of Auris Medical tumbling about 58% from yesterday’s closing share price of $0.825, to $0.35 in premarket trading as of 9:15 a.m.
AM-111 contains brimapitide, or D-JNKI-1 (D-stereoisomer of c-Jun N-terminal kinase inhibitor 1), an inhibitor of the JNK stress kinase coupled to an intracellular transporter. AM-111 is formulated in a biocompatible and fully biodegradable gel and administered in a single-dose intratympanic injection into the middle ear. The drug is designed to work by diffusing through the round window membrane into the cochlea.
HEALOS was one of two Phase III trials launched by Auris Medical to assess AM-111. Auris Medical said it will terminate early the second trial, ASSENT (NCT02809118), a 300-patient study whose design was similar to the 256-patient HEALOS, except that it was designed to measure improvement 91 days after treatment.
AM-111 is one of Auris Medical’s two late-stage candidates. The other is Keyzilen® (AM-101), a candidate designed to treat acute inner ear (peripheral) tinnitus. Auris Medical said today it has completed patient enrollment for the Phase III TACTT3 trial, designed to assess Keyzilen, and expects to report top-line results in the first quarter of 2018.
Auris Medical said TACTT3 has enrolled 741 patients—of which 373 were enrolled within the first three months from tinnitus onset (acute stage) and 368 were enrolled between three to twelve months from onset (post-acute stage).
Last year, Keyzilen failed an earlier Phase III trial, missing its co-primary endpoints in the TACTT2 study—the change in subjective tinnitus loudness (tinnitus loudness question; TLQ) and the change in tinnitus burden measured by the Tinnitus Functional Index (TFI) from baseline to day 84 over placebo. Auris Medical said at the time that Keyzilen also generated more positive results in the subgroup of patients suffering from tinnitus following otitis media, where Keyzilen treatment generated a clinically meaningful and statistically significant reduction of 14.8 points in TFI from baseline, versus 6.2 points for placebo.