Prothena Trial PRX002

[youngparkie]

Massive news coming out of the prothena Trial today

ir.prothena.com/news-releas...

[bassofspades]

Woohooo! And it didn't even mention the mice! Sign me up!

[MBAnderson]

Sounds good, but for newly diagnosed who are not on meds and don't anticipate being on meds for another year.

[WinnieThePoo in reply to MBAnderson]

No. The trial eligibility was newly diagnosed no meds. Meds were allowed year2. If it works it will slow progression at all stages

[park_bear]

"35% reduction in motor function decline" So test arm patients declined 2/3 as fast as control arm.

"The statistical analyses were conducted in alignment with the powering to detect changes at a two-sided alpha of 0.20; thus p-values below 0.20 are considered significant [hmmm]. ... As a result of the primary objective not meeting the criteria for statistical significance, subsequent nominal p-values are for descriptive purposes, without alpha control for multiple comparison." [Emphasis added]

This is only a phase 2 trial so they can say whatever they like, but they would have to do better in phase 3.

" change from baseline in MDS-UPDRS Part III in prasinezumab-treated patients vs. placebo at 52 weeks by central rating (pooled dose levels: –35.0%, –1.88, 80% CI=(–3.31, –0.45), p=0.09". I take it the -1.88 figure is the point difference in decline.

These results are a bit of help, but not an earthshaking change in the treatment of Parkinson's.

If this ends up being synergistic with high-dose thiamine the combined effect would be more useful.

[WinnieThePoo in reply to park_bear]

So, 2 years from now, would you rather your updrs score had increased by 10 or by 6.5?

And as for synergy with B1, royprops latest post isn't very encouraging for progression and B1

[park_bear in reply to WinnieThePoo]

We need the phase 3 result to see if this is real. I agree Roy's result is not encouraging. On the other hand I've been taking high-dose thiamine for more than two years and am about the same as I was two years ago. My current UPDRS score is 25. Did not check my score 2 years ago however.

[WinnieThePoo in reply to park_bear]

I was referring to your "only 2/3 progression" point. When I was diagnosed my neurologist said that stage 1 and 2 were quite well managed by conventional medication and generally last 8-10 years. Imagine if this drug only extends that to 12-15 years

Phase 3 trial will be interesting but it was a large multi-site phase 2. Phase 3 might be in the field

[park_bear in reply to WinnieThePoo]

Phase 3 will be required to have valid stats instead of handwaving.

"nominal p-values are for descriptive purposes"

[Hidden in reply to park_bear]

How does one select a dose of B1 for the slowing of progression?

I understand how you would trial various doses for short term symptom alleviation or an improved sense of wellbeing, but how would you do it for progression? Assuming, for example, that no doses appeared to provide any short term benefits?

[park_bear in reply to Hidden]

It takes 3 to 4 months for most benefits of high-dose thiamine to be observed. I would not call this "short-term" symptom relief. In any case, either the dose that works to improve symptoms reduces, and preferably halts, progression or it does not. If no benefit is observed after four months I personally would not anticipate any improvement in rate of progression either.

[Hidden in reply to park_bear]

How does one "find the right dose" if it takes 3 plus months to see the benefits? Does one have to spend 3 months at every gradual dose level?

[park_bear in reply to Hidden]

No, the dose adjustment adjustment process is not so lengthy. Dosing methodology is set forth here:

highdosethiamine.org/hdt-th...

And has also been discussed in various posts on this site

[Farooqji]

A day of hope to some extent, however it will pass through phase 3 for confirming further (another 2 to 3 years at least}. If successful in phase 3, we can expect it in the market by 2025!

I think some members of this forum were enrolled in the study, they can mention their own experience here.

A bit detailed version of the study results is given in the following link

globenewswire.com/news-rele...

[WinnieThePoo]

I don't think either Redhawk1 or i are too surprised by the news. All the shenanigans on SPARK suggest Biogen will be announcing similar news in a year or so

[Farooqji in reply to WinnieThePoo]

Are you still in the Biogen trial. How is it going?

[WinnieThePoo]

Going ok. I posted about it a couple of weeks ago. Missed 2 visits due to covid19 closures. I have accepted participating in a trial extension

[redhawk1]

I am one of the over 300 cohorts participating in the Roche/Prothena Pasadena study. I was officially diagnosed with PD in March 2017. Symptoms of PD such as tremor in left hand, excessive sweating when exercising and some neuropathy in feet appeared at least two years earlier in 2015.

My first infusion was in September 2017. I can say I had no adverse experience whatsoever Involving the medication at any time.

I do not yet know whether I had the drug in the first year of the two year trial. My symptoms of PD during the two year trial did increase . . . but increased very slowly during the two years of infusion. But, how does one compare progression of the disease not having experienced it prior? lol Since my last infusion one year ago I have noticed a more pronounced progression in symptoms. So, is that “normal” progression of the disease or is it the affect of being without the drug? I did definitely feel my symptoms worsen two weeks after my infusions . . . could that be at all connected to the the half-life of this drug being about 14 days? mmmmm . . .

Although both of my brain docs have recommended that I begin with Sinimet I have not yet done so. I am scheduled to begin phase 3 this coming Wednesday.

So . . . heartening to hear there were signals of efficacy . . .

[Farooqji]

I believe that stem cells Will be the ultimate solution to reversal of PD. The medicines like this (if trials get successful) will only (possibly) halt the progression. The reason is that the restoration of the lost cells is necessary for reversal, which in turn is not possible without harvesting new cells . Mark has rightly pointed out that therapies like these will be most beneficial to the newly diagnosed

[Parkinsonjisung]

Did I understand it correctly that the low dose arm did a lot better than the high dose?

[redhawk1 in reply to Parkinsonjisung]

From my understanding the all phase 3 cohorts will be on the low dose.

[Parkinsonjisung in reply to redhawk1]

Where did you read this info?

[redhawk1 in reply to Parkinsonjisung]

Got that info from contact at trial site. Will confirm that on Wednesday appointment.

[Parkinsonjisung in reply to redhawk1]

Thanks. Interesting that they're moving forward with a phase 3 even before phase 2 has finished

[Parkinsonjisung in reply to Parkinsonjisung]

redhawk1 , any new insider updates on the trial? 😁