A (minor) update by Inhibikase Therapeutics on their Phase 2 trial of Risvodetinib (IkT-148009) for Parkinson's Disease.

[jeffreyn]

As of 24 Feb 2024:

- Recruitment continues and is reaching the halfway point (59 of 120);

- 25 recruits have completed the required 12 weeks of risvodetinib;

"Participant experience in the trial appears to be positive, as clinician and patient impression of disease status or severity is not changing over the 12 week course of dosing."

"Depending on the date of enrollment of the last participant, top line results from the 201 Trial might be reported in the second-half of 2024 [i.e. possibly a little earlier than the Jan 2025 date given in the trial record]."

inhibikase.com/news/press-r...

[jimcaster]

I don't think it's remotely possible to determine if progression has been slowed or stopped in twelve weeks -- unless the disease is actually reversed, which would be miraculous.

[jeffreyn in reply to jimcaster]

Agreed.

And this reminds me that I forgot to mention the planned OLE.

"Twenty-five people have completed the 12 week dosing course and all have indicated interest to continue into the 12 month extension study when available."

[WinnieThePoo in reply to jimcaster]

They're not trying to show that. They're trying to establish that it's safe and tolerable at 200 mg dose. So they can use that dose in a phase 3 trial. The 25 participants are "blind" but roughly 6 of them should be on 200mg. And all 26 want to participate in the open label extension. So it's going really well And the phase 3 won't try to show any disease modifying effect either. It will attempt to show symptomatic relief

And then, if they can get fda approval for that, they will try to show in licensed use, that it is disease modifying. (which we pwp know it must be if it provides symptomatic relief because of its mechanism of action.

Meaning we can start using it about 6-8 years earlier than if they tried to the disease modifying route

[jimcaster in reply to WinnieThePoo]

I understand all that, but other accounts have focused on perceived slowing or stopping progression, which is entirely premature. Even this report says, "Participant experience in the trial appears to be positive, as clinician and patient impression of disease status or severity is not changing over the 12 week course of dosing." That grabs headlines even though safety, not efficacy, is what is being studied at this point. I remain hopeful, but we have a long way to go.

[WinnieThePoo in reply to jimcaster]

It's positive because nobody has dropped out due to a third eye growing in the middle of their forehead or grown scales on their back.No change? 1/4 of them are on placebo. If half had developed a worse tremor or significant bradkynesia then you wouldn't be moving to phase 3

It would be interesting to see the Adpd 2024 presentation instead of just the press release before the event

[WinnieThePoo in reply to jimcaster]

I'm still trying to find the one where he explains why they are looking to show symptomatic relief rather than disease modification. It might be one of the (longer) investment ones

But this video explains the process well, references the 10 year state in mice that I mentioned, credits Michael J Fox Foundation with grant support, and confirms they have a sense of urgency (it also deals with the cause or effect issue on a-syn)

vjneurology.com/video/a6w_5...

[jimcaster in reply to WinnieThePoo]

Like you, I find Dr. Werner to be very persuasive and credible. I also remember seeing the video in which he explained that it was quicker and easier to claim to relieve symptoms rather than actually modifying the disease even if the latter is ultimately true. I'll also look for that video.

[WinnieThePoo in reply to jimcaster]

This would appear to be all we are going to get out of Portugal. Hardly news, other than maybe the state of trial recruitmentparkinsonsnewstoday.com/new...

[WinnieThePoo]

vjneurology.com/video/70ylz...

[WinnieThePoo in reply to WinnieThePoo]

The "change to the trial protocol" which caused them to unblind the first 11 participants, and then restart the trial - was due to an FDA hold order over concerns about eye-related adverse events

Oh - and the "we could completely reverse the disease in those animals no matter how far into the disease course they had gone" is based on mice who were only allowed to progress to the human equivalent of 10 years post diagnosis (I believe). Still very exciting, but it probably wouldn't restore Michael J Fox to pre-diagnosis health

[WinnieThePoo]

59 participants enrolled. 19 prospective in medical screening. Plus 54 potential being evaluated to move to medical screening. If all of the applicants make it to the trial, they have 132 and the trial is full. Hopefully we will have results before the end of this year. And hopefully they get their finger out for a phase 3 at the sort of pace Annovis achieved for Buntanetap. (not easy, because they only want drug naieve applicants). And hopefully they don't run out of money. They were "fully funded" until December 2024. But that presumably means "out of money" after December 2024, since they have negligible revenues and essentially spend money on corporate admin and research projects. Phase 3 is going to be expensive.

Redhawk first due my attention to this drug. The more I look, the more I want it. If it works in humans like it works in mice...

I know, I know - but the mouse science was a bit different from the usual rubbish.

[limcheeese22]

"In 2023, an early insight into the potential of risvodetinib was presented at the annual Movement Disorders Society (MDS) Congress in Copenhagen, where it was shown that 11 patients pulled from the 201 trial in 2022 showed that the sum of Parts 2 and 3 from the MDS Universal Parkinson’s Disease rating scale was reduced by 10.4 points relative to placebo for the 200 mg dose. "

sound really promising, 10.4 points is a lot right?

now phase2 expected to be completed by Jan 2025, that mean we must wait at least 5 more years to be available in the market?

[WinnieThePoo in reply to limcheeese22]

Where do you get 5 years from. It needs a completed phase 3 to be successfulAnnovis bio have just completed a phase 3 of buntanetap 2 years after inception

Why not 2 years from June 2025?

[jeffreyn in reply to WinnieThePoo]

Wouldn't there surely be a sizeable time gap between "a completed phase 3" and "available in the market"?

[WinnieThePoo in reply to jeffreyn]

I'm pretty sure they have an FDA fast track on this one.