Frequency Therapeutics — Hearing Loss Regeneration

I see the secondary outcomes in the Phase 2A as an "AND" not an "OR" as you've suggested. They showed significant improvement in Phase 1/2; so to me, adding more outcomes this early (TFI, etc) is a sign of confidence. Sorry you feel that way.

 

Did you listen to the Tinnitus Talk Podcast interview with Carl LeBel from Frequency Therapeutics by any chance? Why those measures were added was explained.

 

What he said is all great, but the fact remains that they came up with new targets after the study results showed improvements only at 8 kHz and frankly speech-in-noise understanding is not that helpful if there is no change in other frequencies.

 

They did. To expand the evidence that it is working as intended.

Primary Outcome Measures:

1. Speech Intelligibility [ Time Frame: Screening to Day 210 ]
   Assessment of speech intelligibility using the Word Recognition in Quiet test measured with Consonant-Nucleus-Consonant (CNC) word lists.
2. Speech Intelligibility [ Time Frame: Screening to Day 210 ]
   Speech intelligibility using the Words-in-Noise test measured with Consonant-Nucleus-Consonant (CNC) word lists
3. Standard Pure Tone Audiometry [ Time Frame: Screening to Day 210 ]
   Standard pure tone audiometry will be measured to determine a subject's threshold for hearing at standard frequencies (Hz)
4. Systemic Safety: Number of patients with treatment-related adverse events [ Time Frame: Screening to Day 210 ]
   Number of patients with treatment-related adverse events assessed by CTCAE v5.0
5. Local Safety: Number of patients with abnormal changes from baseline in otoscopic examinations [ Time Frame: Screening to Day 210 ]
   Microscopic otoscopy will be included to specifically record any abnormalities of the external ear canal, tympanic membrane and middle ear.
6. Local Safety: The number of patients with abnormal changes from baseline in tympanometry [ Time Frame: Screening to Day 210 ]
   Tympanometry tests the integrity of the tympanic membrane by varying air pressure in the ear canal. Middle ear compliance (mL), peak pressure (daPa), and ear canal volume (mL) will be recorded.

Secondary Outcome Measures:

1. Extended High Frequency Pure Tone Audiometry [ Time Frame: Screening to Day 210 ]
   Pure tone audiometry will be measured to determine a subject's threshold for hearing at extended high range frequencies (Hz)
2. Tinnitus Assessment [ Time Frame: Screening to Day 210 ]
   Measured by the Tinnitus Functional Index (TFI), with a scale ranging from 0 to 100 that defines severity categories based on 25 self-reported answers.
3. Hearing Handicap Inventory [ Time Frame: Screening to Day 210 ]
   The Hearing Handicap Inventory for Adults (HHIA), is a 25-item self-assessment scale composed of two subscales (emotional and social/situational). The subject will self-report one of the following answers for each item on the scale: Yes, Sometimes, No.
4. Hearing Screening Inventory [ Time Frame: Screening to Day 210 ]
   The Hearing Screening Inventory (HSI) is a 12 item self report inventory to assess hearing impairment. The subject will self report one of the following answers, for each question from 1 to 8: Never, Seldom, Occasionally, Frequently, Always, and for each question from 9 to 12: Good, Average, Slightly below average, Poor, Very Poor. The HSI is designed to assess subjective change during the study.

 

This drug has to work. It just has to.

 

You are actually equating a safety study which did some outcome testing with an actual phase 2 study? I am actually at this point yet to see any phase 1/2 study for any treatment that tries to test anything more than the very basic elements of the treatment, which is exactly what Frequency Therapeutics did with their initial phase 1/2 trial. The decision to expand the things tested happens completely regularly with pharmaceutical trials. I can see similar stuff happening with, for example, PIPE-505 if they find out that this treatment benefits tinnitus which is not being tested in the initial trial.

The targets that Frequency Therapeutics set in the phase 1/2 trial actually haven’t changed for the phase 2a trial. Secondary measures do not actually help the treatment getting FDA approval either. Essentially these secondary measures were only added after Frequency Therapeutics found out about additional actual benefits post the phase 1/2 trial that they didn’t know even existed. This is not desperation at all, but rather a case of Frequency Therapeutics trying to get a complete understanding of what FX-322 does.

Definitely have a look at a drug like Viagra which was originally getting tested for heart problems and ended up being able to stimulate men’s privates. No one predicted that was going to happen which was why they added that to testing later too. Thus the amendment of testing criteria is not abnormal and also actually has nothing to do with the performance of the drug in the previous trial(s) either.

 

Well, I think we know what they might call FX-322: RADIAL.

https://uspto.report/TM/90263339

 

In most of the literature it's discussed that tone matching is incredibly difficult to achieve for the average patient population, and time-consuming for the audiologist.
In my personal experience, most audiologists also care little for the diagnostic information like tinnitus match, loudness and masking levels. Probably because they haven't got any idea how they can put this data to good use.

 

It says it's for an "assessment" protocol. Is that just standard wording?

 

I saw that as well, in my experience with trademarks, they are broadly worded on purpose. It could be that FX-322 is part of some type of Frequency Therapeutics' own "regenerative" treatment process. IE: Using the "RADIAL" process to treat hearing loss with their regenerative drugs.

 

I just noticed that they marked it as category 101. So, it may or may no be a product name, but could be an "advertising" asset. Since they're calling it an "assessment" and classified as an advertisement, it's much more likely that RADIAL is being used as an instrument to inform. So, in my revised opinion, Frequency Therapeutics may be developing for informational/adverting purposes a "RADIAL" process/assessment to inform doctors/ents how to assess hearing loss and then how that assessment applies to delivering FX-322. It would make sense for Frequency Therapeutics, since they own the rights to the drug, to also begin taking ownership of the process for informing doctors of delivering and administering the drug.

This might be a sign that they're already working on how to quickly educate ENTs on understanding how to assess hearing loss in patients, and perhaps how many injections are needed to begin recovering those losses.

 

Radial would be a bad drug name, doesn't sound drug enough.

 

FX-322 safety study took place in 2017 (Phase 1). Phase 1/2 was indeed rather strange, because the primary target was still adverse events. I think the Phase 1/2 was designed in a way to be successful for upcoming IPO. They hoped to also demonstrate efficacy, but not as the official target, however this part did not quite materialize. So it is quite reasonable to consider that even multiple injections might not provide desired results, hence the new secondary targets were added to Phase 2a.

 

I agree that they probably thought they'd see better performance on the audiogram from the Phase 1/2. But, it does seems like the significant word score improvements seen out of the Phase 1/2 was an unexpected "win" for them.

 

An initial injection is needed to start the regeneration process and subsequent injections will be more effective at penetrating the cochlea.

 

Phase 1/2 was still acknowledged as a safety study by the FDA for the fact that it was the first time that Frequency Therapeutics used the large dose in a trial. Thus they were only allowed to test a single dose of FX-322 during this trial.

The thing is that the secondary targets do not actually assist the medicine in getting FDA approval and Frequency Therapeutics still hasn’t changed their primary targets from the Phase 1/2 study though either. You might also need multiple shots to work to achieve some of these secondary measures though which rules out the claim that these have been added because Frequency Therapeutics didn’t get certain results in Phase 1/2.

Therefore I cannot see how you can equate adding secondary measures to a trial for reasons such as Frequency Therapeutics wanting to demonstrate that the medicine works, when Frequency Therapeutics hasn’t actually shifted away from its primary aim with the medicine and actually only added these when they discovered that the medicine provided a far greater benefit than what they initially thought that it would.
Efficacy also got demonstrated with the improvement in word recognition scores.

 

7 months till we all get the answers that we seek. Praying on Breakthrough Status.

 

If you could get both FX-322 and OTO-413 injected at the same time (same day), would the effects of OTO-413's hydrogel carry over to FX-322, or would the two have to be mixed prior to injection for that to happen?

 

If FX-322 doesn't work I'm literally moving to Central/South America and living in a lean-to. We can start an open-air community in a habitable climate for tinnitus sufferers.

 

Was thinking of moving to Oregon somewhere off the grid and growing marijuana. I am done with society.

 

You know it’s funny, I was thinking that once they are both out, I wonder if they’ll ever make a blended version like we have now where they mix Paracetamol and Ibuprofen.

 

Probably not since they're both made by competing companies. A combination of OTO-413 and OTO-6xx is more likely. I'm thinking more along the lines of convincing an ENT to do it.

 

If it works better in combination, then yes, I think that Otonomy will combine both OTO-413 and OTO-6XX but it is going to require separate safety and efficacy trials since it effectively becomes a new treatment.

Have faith. If it isn’t FX-322, I reckon something else is going to work.

 

And if a success, instant compassionate use availability.

 

I’m hoping that after Phase 2a, the results are good enough that it can come to market before the Phase 3 trial starts.

 

Absolutely this. I hope all the back end stuff Frequency Therapeutics has done is indicative of FX-322 working because this gives me a lot of positivity at present.

 

Is this actually a possibility?

 

Yes release after Phase 2a is possible for a number of reasons:

1. Frequency Therapeutics has been granted Fast Track status and compassionate use allowance by the FDA because FX-322 is a new medicine to treat an unmet need. This enables Frequency Therapeutics to release the medicine if it successfully completes and passes phase 2 trials under the ‘Right to Try’ and ‘Compassionate Access’ provisions if they choose to so.

2. Commentary from Frequency Therapeutics staff has indicated that they would be open to considering allowing early access to FX-322 if they believed it delivered outcomes which warranted early release/access.

3. There is clear desire and interest from consumers in getting FX-322 at the earliest possible time. This means Frequency Therapeutics stands to benefit earlier with sales than they would if the medicine was not actually released until after completing the full trial process first. Furthermore customers could get FX-322 much sooner as well.

4. Fortunately ear medicine and specifically ear medicine which treats hearing, has a very low chance of delivering false results which don’t indicate the true outcomes and/or true effectiveness of the medicine.

This means that if trial participants gain improvement(s) with FX-322, it is highly likely that these are genuine and also real outcomes which would be validated by the FDA. This means the FDA can be very confident that FX-322 is working as it is expected to.

The previous trial demonstrated that various stakeholders could be confident in the trial result when only those who were given FX-322 demonstrated hearing improvement.

5. it is quite obvious that Frequency Therapeutics has focused solely on completing the trials in the US first for two reasons:

Firstly, because trials in the US are relevant and required to get FX-322 approved in the US by the FDA.

Secondly, completing the final or pivotal trial(s) overseas has no bearing on whether Frequency Therapeutics can obtain approval from the FDA to release FX-322 through compassionate use allowances. Companies are only required to complete one trial in the US and Frequency Therapeutics are doing this by completing the phase 2a trial there.

Therefore the FDA will recognise future trials including the final or pivotal trial conducted overseas by pharma companies based in the US.

So by completing trials in the US first, Frequency Therapeutics will have done what is required to release the medicine in the US under both the compassionate use provision and to get the final FDA approval.

This means Frequency Therapeutics can start selling the treatments in the US as soon as possible, obtain their payment from Astellas for running the trials in Asia and Europe and still successfully comply with the overall requirements to fulfil the FDA process.

Therefore I think that it is truly possible that Frequency Therapeutics might release FX-322 after phase 2a providing it actually satisfies the FDA requirements.

While Frequency Therapeutics will get in trouble if they directly comment that they are going to release FX-322 through compassionate access, we know they have indicated many times and through many platforms that they have a clear desire to help people as quickly as possible. Furthermore I feel that Frequency Therapeutics have certainly laid the framework to potentially be able to release FX-322 early after the current trial is done.

So I would say that an early release post phase 2a does currently seem to be very possible.

 

Yes it is possible. I'm not going to guess the likelihood of this or how it would go because I'm not sure but if the results are deemed to be above a certain level along with a good safety profile and there is an unmet medical issue that FX-322 addresses, it can be released while phase 3 is being conducted.

However, if people can access FX-322 early, I can see it messing with phase 3 trials, since getting and retaining trial subjects might be more difficult. Why go through the possibility of getting a placebo when you can get the real thing? Only reason I can see is financial. Some people may not be able to simply afford the treatment and would depend on being a trial subject.

 

You raise some very good points on the potential accessibility of FX-322 after Phase 2a. As a counterpoint, the primary issue would be the findings of the study from only 95 participants.

Given the limited variability of audiogram scores after treatment, the cost factors for the procedure, and possibly hindering any conclusive strong backing that a Phase III would probably provide, I believe Frequency Therapeutics will elect to proceed with Phase III given the financial backing that was received from investors in August, 2020 for the sole purpose of financing further testing. This company is hell bent on leaving no stone unturned and patience is key.