Unlikely at all IMO, a lot of members here have been shot up with all sorts of stuff and noticed no improvements, and most people here can attest that time does nothing at all.
Frequency Therapeutics — Hearing Loss Regeneration
- Thread starter RB2014
- Start date
Member- Aug 5, 2019
- 1,852
- Tinnitus Since
- 05/2019
- Cause of Tinnitus
- Autoimmune hyperacusis from Sjogren's Syndrome
There are people who see great improvements by chance, either with lower stress, better sleep, better diet, coincidence.
ajc
Member
- Feb 6, 2018
- 1,170
- Tinnitus Since
- 11/2002; spike 2009; worse 2017-18
- Cause of Tinnitus
- Loud music - noise damage
You are very wrong. MOST who get tinnitus habituate to it, it becomes a non-issue or it improves considerably over the first year or two.
This forum is not representative of the real world.
Imo you are stuck on "the drug barely works" without understanding *why* it would work differently in different people and just going population stats. Doubling word scores is not subtle.
At least consider this possibility: the drug targets IHCs first, but with either pristine IHCs or multiple doses, it would target OHCs.
If rapid multiple dosing diminished this effect, we have no idea how well it could work for OHCs, but even small gains could be improved with re-dosing at more reasonable intervals.
It's just not consistent to me to say doubling word scores in Phase 1 is not placebo or chance but the "drug barely works." The "why" of the data has to be answered first.
- May 27, 2020
- 556
- Tinnitus Since
- 2007
- Cause of Tinnitus
- Loud music/headphones/concerts - Hyperacusis from motorbike
It's all plausible, although I find it difficult to explain tinnitus changes given it was previously stable for two years. I know you're being bearish for the sake of us all not getting ahead of ourselves, but I think your gut might be telling you otherwise.
The takeaway for me from my conversation with this patient is that if you put the tests aside, this patient is experiencing real life, translatable benefits. The problem we have is that these are not being reflected well enough in the endpoints, possibly due to subpar diagnostics. I'm not even going to start on subpar dosing and delivery. It's kind of sickening to think that this drug could fail not because it doesn't work but because the tools at our disposal are not objective or accurate enough to track what the drug is doing in real terms so that the FDA can approve it until Frequency Theraputics can optimise dosing and delivery.
- Aug 5, 2019
- 1,852
- Tinnitus Since
- 05/2019
- Cause of Tinnitus
- Autoimmune hyperacusis from Sjogren's Syndrome
Well, my answer to this is that I do believe super responders are possible, but it's probably small for most true responders. I'm not sure what doubling has to do with this patient, as they improved by 10%.
I'm sure you would agree with me on this, it's more than just OHC vs IHC distribution; there could be reasons that we don't understand as to why some handle the bad delivery better than others.
Let's say this patient saw a worsening. Similar margins. Would we think they were the placebo?
This person had hearing loss for over two years and he noticed his tinnitus to be 90% gone 3.5 months after the last FX-322 shot. I don't think this is a coincidence, I think FX-322 did something.
I'm talking about mechanism (which previous results give us clues about), not just this patient and it is extremely relevant to the variability.
But if we were to take this patient, for instance, and my theory is correct, they still wear hearing aids but some sounds are "easier to discern". They have 3 bands of 10 dB changes. This could easily fit with the drug preferring IHCs but had minor OHC changes probably on second pass but dampened by rapid repeat dosing.
There is a lot to uncover here...
Are these people reporting these things to FREQ? With these kinds of results the FDA could be very flexible.
- Aug 5, 2019
- 1,852
- Tinnitus Since
- 05/2019
- Cause of Tinnitus
- Autoimmune hyperacusis from Sjogren's Syndrome
Being a bear sucks, especially on a support forum, but I'm trying to ask fair and critical questions.
This patient does not scream treatment to me. If their word scores went from 40% to 80% and they are as honest as you think they are, then I would change tune for this one patient anyways.
FYI, with a starting word score of 40%, the upper bound of the 95% CI is 58%. They weren't statistically significant. I'm too tired to compute the p-value, but it's quite a bit bigger than .05. I haven't looked at the PTA stats as much, but 10 dB is not unbelievable.
But what if Frequency Therapeutics are right and multiple injections do dampen the effect?
This is why I have been saying over and over again, that we now need more data (eg. the severe arm).
- Aug 5, 2019
- 1,852
- Tinnitus Since
- 05/2019
- Cause of Tinnitus
- Autoimmune hyperacusis from Sjogren's Syndrome
I see. Sorry, I get confused sometimes (and I'm going to bed now) whether we are talking about diagnostics and discovery or the overall population-level proof required in the study. As I've said before, case studies have a really important place in medicine; it's just not for proving efficacy.
I agree, we only need the age-related hearing loss trial to show meaningful improvements and maybe show some patients with a decrease of their tinnitus or completely get rid of tinnitus to convince the FDA that FX-322 works with patients with mild-moderately severe hearing loss.
Why should millions of people have to suffer from the delay of the trial while most people have only mild-moderately severe hearing loss.
- Aug 5, 2019
- 1,852
- Tinnitus Since
- 05/2019
- Cause of Tinnitus
- Autoimmune hyperacusis from Sjogren's Syndrome
If there's anything I've learned, it's that the burden is on the data to prove the theory. Frequency Therapeutics also said that multiple injections could push the drug deeper.
For the Severe study, even if it is successful, that's changing two big variables in one study: hearing loss level and single vs multiple injections.
We still don't have proof of the dampened theory. We really would have some level of proof for the dampened + moderate combined.
Even then, it's a shame the sample size is smaller for the Severe study. Would be great if we could basically redo Phase 2a with one injection and only Severe...
As long as absolutely none of the placebo group improves and that the FX-322 group does improve. I reckon if just one of the placebo patients also improves it will cast a huge doubt over not just these Phase 1bs but also Phase 1/2.
I thought about that as well. Maybe IHCs and OHCs are both growing but OHCs are having trouble with the synapse and IHC are not.
Totally get where you're coming from @Zugzug — and appreciate your valued input as always, especially taking a bearish approach — but maybe a 10 dB shift can have massive implications in terms of tinnitus reduction depending on type of damage and location of frequency.
We simply do not know how much regeneration is necessary to generate enough input that would result in a noticeable improvement of tinnitus since there's so much variation amongst individual cases.
I would also like to add that both of the positive anecdotes stated they think they may have gotten two FX-322 shots as they noticed the shots give a burning sensation.
@Aaron91, would you be able to ask those positive anecdotes about when they got their 4 doses, and in which order of those 4 shots did they experience the burning sensation. I'm trying to figure out if they got two shots of placebo first and then two shots of FX-322 or if they got FX-322, Placebo, Placebo, FX-322, etc. I am trying to figure out why they may have experienced those improvements where other participants didn't.
@Aaron91, would you be able to ask those positive anecdotes about when they got their 4 doses, and in which order of those 4 shots did they experience the burning sensation. I'm trying to figure out if they got two shots of placebo first and then two shots of FX-322 or if they got FX-322, Placebo, Placebo, FX-322, etc. I am trying to figure out why they may have experienced those improvements where other participants didn't.
Maybe they burned themselves. They added some 'soft' criteria to increase their chances of getting a good result. If they had stuck to the published criteria and maybe added extra total numbers to get enough subjects with low WRS scores, maybe things would have been different. I think their first mistake was treating the Phase 1b as a defacto efficacy trial. They wanted the publicity. The next trial should have been the same regime with bigger numbers.
Wouldn't it make sense then to abort the Phase 2a trial and get on with the post-mortem? Preferably with third party assistance imo.
These are my before and after audiograms:
Look at the dates and then look at the difference at various frequencies. This could be construed as an improvement, but I didn't have a treatment of any sort. I took various vitamins and that's about it.
My right ear, in particular, went up by 15 dB at 8 kHz. This is the issue I have with results that show an improvement of 10 dB. It is clinically insignificant and means nothing. This was made clear by Frequency Therapeutics themselves when 4 people showed an improvement of 10 dB in phase I/II just like I did (except I didn't have FX-322).
I also think the WR scores are too marginal. It's very underwhelming.
An anecdotal experience of someone noticing an improvement in their tinnitus is common amongst the general population.
There's no other way I can view this. I need to see hard data that proves beyond doubt that FX-322 is doing something inside the ear.
That is my biggest fear that both placebo and FX-322 show improvements. I hope none of the placebos show improvements and nobody fakes their word scores before the trial because that's what really cost us in the Phase 2a.
That's why I hope both age-related and severe hearing loss trials show improvements in FX-322 and none in placebo. I'm not that confident about the severe hearing loss trial as FX-322 will need to go deeper in the round window.
That's the problem with having these types of hearing conditions as each person is different and it can be really hard to test what type of hearing loss they have.
I agree with this, their biggest mistake was doing multiple doses of FX-322. They should have done a single dose again with more people to confirm that it works.
As the saying goes "they bit off more than they could chew"
Some good news, their stock is at $9 now. And they still have $200M.
A setback? Yes. But they are not done, not by a long shot.
A setback? Yes. But they are not done, not by a long shot.
Street Novelist
Member
- Apr 2, 2018
- 290
- Tinnitus Since
- February 2018
- Cause of Tinnitus
- Listening to loud music through headphones
I hope Lucchino's theory is correct; that they just need to wait before giving us a second injection and so on. I'm telling you, if this drug doesn't end up working, I don't think I'll be able to take on life anymore.
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