It depends on who you ask, but how I have looked at these results was the same as Dr. Cliff in the video that
@Keith Handy posted, which is the drug seems to prefer IHCs vs OHCs.
IHCs are difficult to test for because you have to lose a lot of them before it shows up. Just like OHCs, it is a cause of tinnitus (there isn't just one structural cause) in individuals who have IHC loss (which you would only suspect if you have lost a lot of them).
I still very much believe the drug grows OHCs too (pre-clinical explant studies show this) but IHCs are preferred first pass and rapid multi-dosing produces worse results. I contend that we therefore cannot conclude what it does for OHCs without multi-dosing at much longer intervals.
Anyway, the problems Frequency Therapeutics has attributed to Phase 2a failure are:
-- Rapid multi-dosing worsening outcomes (which is not that uncommon just based on the fact that more isn't always better for efficacy, e.g., SPI-1005 did worse for efficacy at 600 mg vs 400 mg), even if they don't exactly yet know why (could be anything from overdosing to fluid overload, e.g., inducing temporary mild Meniere's type environment, interfering with signaling, multi factorial?).
-- "Inconsistencies" in word scores that Frequency Therapeutics said they found in medical records vs the baselines. I.e. people worsened their word scores to be selected.
There has been some back and forth about how many people that could possibly be, however, widespread IHC destruction much more commonly happens with severe hearing loss (there are exceptions but it's not the norm) and Frequency Therapeutics selected Phase 2a participants based on excluding people with Severe PTAs (they were put in the severe trial instead) while making low word scores a requirement. They were essentially giving a huge preference to people who would lie about their word scores inadvertently.
There is still a delivery problem below some unknown range between 6 kHz and 8 kHz based on pharmacokinetic data they had released earlier but, ironically, if they are delayed 2 years due to redoing Phase 2 with a different trial design, they may be able to piggy back a better delivery technology (Otomagnetics, less destructive surgery, etc.).
Some people think the Phase 1 and Phase 1b word score results were fraud (I don't at this point) or placebo (I don't believe the placebo effect applies to things that have historically not been possible).
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