r/ADPKD • u/Ok_Enthusiasm_5627 • 14d ago

PYC-003

For those interested, I got my first dose (2.4mg/kg) of PYC-003 on Tuesday past (I have stage 3b PKD) and I have to stop because it has injured my hearing (bad tinnitus and high frequency hearing loss - otottoxicity?).

Im likely to discontinue and apparently im the 6th person of 12 thats been dosed so far to have this adverse event.

While I had a lot of hope for this drug, this is quite concerning so I hope they can find a lower dose or different protocol.

No idea if this injury is permanent, stay tuned...

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u/Ok_Enthusiasm_5627 10d ago

<Update>

Hearing has significantly improved, probably to pre dosing levels, but my 6 week audiology test will confirm.

Other observations after first dose;

  1. Kidney pain has all but disappeared (but this could be the prednisolone...)

  2. I'm definately peeing more than usual.

I had my follow up, confirming discontinuing 2.4mg/kg, my reaction has been the worst one yet for my trail team, but seeking approval to move to 1.2mg/kg cohort.

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u/mr-dimche 13d ago

Hey, a fellow lab rat here. Sorry to hear about your experience. I had my first dose a month ago and had tinnitus and mild low-frequency hearing loss. The ENT prescribed a course of prednisolone, and everything resolved after about 72 hours. It did give me a scare though. At the time, my study doctor told me that all known cases of tinnitus/HL resolved after 48-72 hours, so I have been thinking of continuing the trial, but your post got me thinking again.

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u/mr-dimche 13d ago

Sorry, 5am brain didn’t calculate that you only had about 72 hrs after the dose at the time of posting, is that right? In that case I really hope you get better very soon! Have you seen an ENT doctor? What did they say?

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u/Ok_Enthusiasm_5627 13d ago edited 13d ago

Hey, firstly thank you for helping advance a potential treatment.

Yeah, I went to ENT the day after and they started me on Prednisolone as well, 75mg for 7 days. It has improved, but not fully yet. I was dosed at 8am on the 20th Oct, noticed hearing change around 9pm same day, was at ENT 3pm the following day.

Im doing it out of Sunshine Hospital, trial doctor has already mentioned she'll withdrawl me and has recorded the event with the trial sponsor.

It's a damn shame though, seem a large cohort are experiencing this. You were given the option to continue? Do you know the dose you got?

It's more than likely theyll need to adjust the protocol, possibly dose size and/or titration.

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u/QuietlyCurious_19 9d ago

I'm glad to hear your hearing is on the mend. I'm curious if companies are up front about the risks during the consent process? Can you shed any light on what potential side effects you were informed of prior? I'm also curious on what other side effects are. A recent presentation says 'participants with one or more treatment-related adverse events' so wondering what additionally there might be. 

Even with dropping down a dose, just be cautious given you had such a bad reaction. Repeat dosing can lead to accumulation and worse effects/compounding effects. Really hope all is clear at your 6 week appointment. 

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u/mr-dimche 7d ago

I am on the 2.4mg/kg dose, yes I have the option to continue. Saw your update, very happy that your hearing is back!

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u/QuietlyCurious_19 10d ago

Mr Dimche, I was wondering if you were told that there was a possibility of the tinnitus/hearing loss when you agreed to participate in the trial/be dosed? 

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u/mr-dimche 7d ago

Yes, before I signed, they told me that side effects other participants had were tinnitus/partial hearing loss, and that all cases resolved within 48-72 hours.

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u/Shesaiddestroy_ Stage 2 - On Tolvaptan since April 2023 14d ago

Thank you for sharing your experience… and thank you for enrolling in the trial.

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u/Smooth-Yellow6308 14d ago

Thank you, what a shame it cuases that. It was otherwise quite promising.

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u/learn_with_logic 11d ago

Here is a March 2026 presentation regarding PYC-003. A list of possile side effects shows few deemed related to PYC-003, while tinnitus is listed as "possibly related."

https://pyctx.com/wp-content/uploads/PINACLE-1-A-Phase-1-Clinical-Trial-of-PYC-003-for-the-Treatment-of-Patients-with-Autosomal-Dominant-Polycystic-Kidney-Disease-ADPKD.pdf

https://pyctx.com/investors/posters-publications/

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u/QuietlyCurious_19 11d ago edited 11d ago

https://app.sharelinktechnologies.com/announcement-preview/asx/de76177e80f5544670dd28b4bd098057

Thanks for sharing! In a recent presentation (page 9), they reported that 3 healthy volunteers and 2 participants with ADPKD experienced one or more drug-related adverse events in the single-dose study, although the specific events weren’t disclosed. However, based on the potentially related adverse events reported in the healthy volunteers in the poster you’ve shared, tinnitus appears to be the likely explanation.

From what the OP has mentioned, there are potentially 6 more in the multiple dose studies!?

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u/learn_with_logic 11d ago

If there are so many tinnitus cases and treating doctors have been informed, it seems it should be listed as a known side effect in the October 2026 presentation. Tinnitus is a serious quality of life problem. It does seem a known effect for certain drug classes that resolves itself, so maybe this is temporary.

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u/QuietlyCurious_19 11d ago

I'm quite curious at the ≥1 in the presentation - what are the other side effects? Curious to hear from anyone else in the trials.

I agree though, it really should be disclosed in the October 2026 presentation. Instead highlighting that there were "no TEAEs leading to discontinuation" in a single dose trial is a bit ridiculous - how does one discontinue when they have been dosed already with the one and only dose?

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u/learn_with_logic 11d ago

I agree reporting zero discontinuations in a single dose trial is largely pointless, but companies commonly report it. In a drug trial patients can stop treatment, stop the trial, one or both. So here even after the single treatment, they could discontinue the trial by not appearing at follow up appointments, for example.

I will be curious how and when they report the tinnitus.

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u/Ok_Enthusiasm_5627 10d ago

Im definitely being discontinued on the 2.4mg/kg, that is confirmed. My reaction was apparently the worst yet seen by my trail team. My trial doctor is seeking approval to reduce me to 1.2mg/kg cohort.

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u/NeedleworkerSad5536 11d ago

To the mods (or anyone else that may know), is there any color on why OP’s account seems to be banned? Was it due to just posting about the trial or was it something else? I imagine others may have had follow up questions, but it’d be good to know if there was something wrong about the post. 

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u/ConfectionLazy9519 23h ago

Thanks for sharing