So... if they cherry-picked the most likely subjects to give positive results, the results are really only applicable to people who meet the same selective criteria.
How's the FDA going to view that? And on different but kind of related tack, if the results are positive, investors are going to make decisions unaware (most of them) that the subject pool may not be representative of the general hearing loss population (the hundreds of millions that we were told had an 'unmet need').
I throw that over to the hive mind.
There are two points to unpack here. The first point is one on efficacy and FDA approval, your other point has to do commercialisation risk.
On your first point: the FDA will view it quite favourably, in fact. Remember, half the bear thesis (not put forward by bears, but by bulls with concerns) is that Frequency Therapeutics may not be able to successfully "cherry-pick" the population well enough to produce statistically significant results that will allow them to move on to Phase 3 in the first place. The FDA are
not asking:
"Does this drug treat hearing loss of any and every kind and can that be shown at a statistically significant level in all groups"?
Instead, they are asking:
"Does this drug treat hearing loss for at least some kind of population at a statistically significant level in any group"?
Just because there is an unmet need in all groups doesn't mean a drug won't be approved only because it still meets some kind of unmet need.
There's also a wider point to be made here and that is people can get really, really bogged down in the maths sometimes, especially the bears. Just because there were 6/15 "responders" doesn't mean those 9 other patients didn't experience some kind of quality of life improvement that wasn't necessarily reflected in WR/WIN/audiogram tests. As Frequency Therapeutics have said in their KOL presentation, just a 10% improvement can translate to a huge quality of life improvement. A case in point here is Sarepta and their DMD drug Exondys 51 (thanks to
@FGG for bringing this to my attention). If I remember correctly, the drug could only be used in 14% of cases of DMD and if you looked at the maths and trial design even their results could have been described as somewhat spurious, especially compared to Frequency Therapeutics. And yet when you looked at patient testimonies and how the drug translated to real life, you had examples such as the one
@FGG described of a kid that should have been in a wheelchair but was skiing! So all this to say that quality of life improvement as a measure is a real thing and that is, I suspect, one of the reasons why a secondary endpoint is the Quality of Life questionnaire just to cover all bases. I'm going to go out on a limb and say that in the event we do not see statistically significant improvements in the mild hearing loss category, that does not necessarily mean we won't see a statistically significant QoL improvement in that same category.
All this brings me to your second point about commercialisation risk. I think I speak for a lot of us here when I say that just because some of us may not fall within the group parameters that showed statistical significance, that doesn't mean we are not willing to try this drug when it gets to market. We shouldn't underestimate how far a person will go when they are desperate, particularly when their health is on the line. This thread is a case in point: over 500 pages of debate and research. I come back to a quote I quite like: "a healthy person has a thousand wishes, a sick person only one". Assuming this drug costs something in the region of a hearing aid (which only has a 25% uptake rate due to stigma/aesthetics/crudeness of technology/ineffectiveness with regards to clarity), I think most people with hearing loss of any kind would be willing to give that a shot.
I think they will definitely have enough tinnitus patients considering the age-related cohort was in another trial and >90% of people with SSNHL have tinnitus:
Sudden Sensorineural Hearing Loss; Prognostic Factors
I quite liked
@Diesel's take on this. I think it's very plausible that a selection criterion could have been tinnitus in the treated ear and not the other. How difficult that would have been to recruit for though I have no idea, especially if we also assume the other boxes they would have wanted ticked, such as asymmetric hearing loss etc. I suppose it's possible though that if you have asymmetric hearing loss, chances are that if you unilateral tinnitus, it's more likely to be in the bad ear than the good ear.
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