Since it is some +3 years ago I created this thread in the slipstream of the Summer of 2014 after I had had multiple dialogues with Autifony Therapeutics as well as some of the personnel at the study centres, I wanted to briefly return for a "comment or two".
From my perspective, it is not clear what Autifony Therapeutics has in store with the overhaul their pipeline has received in relation to hearing disorders. At this point, just the target (Kv3.1 channels) is mentioned, not the compound they intend to use. This is relevant because in the
latest paper (paywalled), AUT00063 was the compound of interest and the earlier failed clinical trial (QUIET-1) which employed AUT00063 was specifically referred to in the conclusion – which is not included in detail in the abstract (but the excerpt can be seen below for those without access):
"The suppressive effects of AUT00063 on spontaneous activity are important from a clinical standpoint because increases in spontaneous activity have long been known to be a neural correlate of tinnitus. The observed suppression of hyperactivity in the present study, therefore, suggests that AUT00063 may have a suppressive effect on the tinnitus percept in humans.
A double-blind, placebo-controlled trial of the efficacy of AUT00063 in patients with subjective tinnitus, sponsored by Autifony, was recently completed in the U.K. (NCT02315508, ClinicalTrials.gov). Unfortunately, the trial did not meet its primary endpoint, which was a reduction in tinnitus score measured using the Tinnitus Functional Index (TFI). Plasma levels of AUT00063 in subjects were similar to those achieved in rodents following a 30 mg/kg i.p. dose.
The apparent absence of effect of AUT00063 in this trial likely reflects the heterogeneity of the tinnitus population studied and the possible insensitivity of subjective rating scales such as the TFI to changes in tinnitus percept. In addition, whereas the present preclinical study examined activity immediately following drug administration, the clinical trial outcomes measures were obtained 28 days following treatment. It will therefore be important to assess the persistence of the effect of AUT00063 in the rodent model with chronic dosing. More direct measures of auditory brainstem neural activity in patients would also be useful to allow a better translation of rodent study results in humans."
So, what the above means is that:
- Autifony Therapeutics could be revisiting AUT00063 once more (due to the observations mentioned above re: clinical trial design in relation to the 28-day observation timepoint).
- Autifony Therapeutics could be moving forward with AUT1 or AUT2 (which were already described in a comparison publication in 2016. I recall finding it odd at the time, that new publications were surfacing and decided not to do much with the information (in part because "tinnitus" was not mentioned even once in the entire paper – if I recall correctly).
Of course, a possibility is also that tinnitus is not "on the menu" at all, but instead problems related to hearing clearly with background noise present, or... something else altogether.
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