Results for Prothena’s Phase 1b Multiple Ascending Dose Study of PRX2/RG7935 in Patients with Parkinson’s Disease to be Presented at the 13th​ International Conference on Alzheimer's and Parkinson's Diseases | P&T Community

For those who might have missed it, the results from the preceding Single Ascending Dose (SAD) trial were published late last year:

First-in-human assessment of PRX2, an anti–α-synuclein monoclonal antibody, in healthy volunteers - Schenk - 216 - Movement Disorders - Wiley Online Library

(this is an open-access document)

and here is the trial record for the recently-completed Multiple Ascending Dose (MAD) trial:

Multiple Ascending Dose Study of PRX2 in Patients With Parkinson's Disease - Full Text View - ClinicalTrials.gov

Here's a link to the December 2016 article on PRX002's Phase 1 clinical trial results. My key takeways:

- PRX002 can clear alpha-synuclein from serum (blood)

- The trial didn't measure whether it did this in the CNS (i.e.: cross blood-brain barrier)

- In mice given a model of PD, they did measure it, and indeed PRX002 did clear alpha-synuclein from the CNS, leading to improvement of PD symptoms

- Phase II trial is slated for 2017 --- exciting!

- Alpha-synuclein exists in many forms, some healthy, some unhealthy. PRX002 clears them all, but has a preference for aggregates over single molecules. Unclear as to whether the clearing of healthy alpha-synuclein is a problem, though it did not lead to symptoms in the healthy patients in the phase I trial. Still, this is cause for concern.

- PRX002 works by binding to alpha-synuclein, apparently in a way that the result can be cleared by the body's own house-cleaning systems (autophagy). This is good, since the alpha-synuclein found in PD cannot be so cleared, hence it builds up. Translating it from unclearable to clearable is a big deal.

- It will be exceptionally interesting to see whether this can be proven to be as good in people with PD as it was in mice given fake-PD. With this in mind, as well as other drugs in the pipeline, my focus for my own PD remains squarely with doing whatever I can to slow the progression. For me, this includes: exercise, diet, intermittent fasting, rasagiline (yes, the last one is controversial).

-- Dan

Darn - I have less than 10 posts, so it won't let me post the link. Would someone please reply to this post, after re-assembling the following link. -- Dan

onlinelibrary.wiley.com/ doi/ 10.1002/ mds.26878/ full

Dan,

The link you wanted to post is actually the first link in my post (i.e. the post just above your post).

Jeff

... and here is a link to the just-announced results of the multiple-ascending-dose (MAD) trial:

Clinical Results Presented from Prothena's Phase 1b Study of PRX2/RG7935 Demonstrating Robust Antibody CNS Penetration and Significant Reduction of Free Serum Alpha-synuclein in Patients with Parkinson's Disease (NASDAQ:PRTA)

Quick summary:
- the Phase 1 trials were successful;
- a global Phase 2 trial of approximately 300 patients with early PD is planned to commence in the second quarter of 2017.

Thanks Jeff. The latter link is the one I meant to paste in. Hopefully, in a couple of years, there will be less of those kind of errors

Dan

Am I correct in thinking that this drug, if it pans out, would potentially be effective for most people with PD, since it is designed to remove alpha synuclein from the brain? No matter how one acquired PD, toxic chemical exposure, gut dybiosis, genetic ddefect, head trauma etc., an aggegation of alpha synuclean in the brain results in PD.
If all trial phases are favorable, how long do we have to wait before this drug is available? Thanks

At this time, the working theory for the vaccine/anti-body trials does not account for any differences in the etiology of the disease. That's not to say, though, that there aren't differences. But, it's so hard to get these trials approved and funded as it is, none of the companies involved want to entertain the possibilities, at this time, of sub-categorical differences. It would require huge sample sizes and take too much time.

With regard to timing, unless there are changes in FDA regulations, it's not likely to be anytime soon. This phase 2 won't conclude for 3 1/2 years (Oct 2020) if everything goes perfectly. Then, assume at least another year to get a phase 3 designed, funded and approved. Then another 3 1/2 year to complete that study. Then at least another year for filing and approval of an NDA. So, I would think around 8 more years. Of course, anyone on here who is still early stage (less than 2 years) can try to enroll in the trial and get the infusions immediately, assuming you don't end up in the placebo group. I would definitely consider it if I was eligible.

Let's just hope that it actually has efficacy. Just take a look at the numerous vaccine failures in phase 2 for Alzheimer's (Merck, Biogen and others). Of course, they all worked on Amyloid-Beta while the new target of choice is now Tau.

For those who may be interested in enrolling, the trial will begin recruitment in June. You can see the inclusion criteria and locations here:

A Study to Evaluate the Efficacy of RO74615 in Participants With Early Parkinson's Disease - Full Text View - ClinicalTrials.gov

Blackfeather said: ".... an aggegation of alpha synuclean in the brain results in PD."

It is my understanding that this has not (yet) been proven, although it is fairly safe to say that an aggregation of alpha synuclein in the brain is associated with PD.

As Tupelo3 said: "Let's just hope that it actually has efficacy."

IMHO, they might end up (eventually) finding that PD results in an aggregation of alpha synuclein in the brain, rather then an aggregation of alpha synuclein in the brain results in PD.