Phase 2 trial of Nilotinib

[parkie13]

parkinsonsnewstoday.com/201...

This just showed up in my email box for Parkinson's news today.

[FMundo]

The funniest thing.... it showed up in my email box as well ! I am a participant in the current Nilotinib trial being run by Georgetown University. There are a couple of corrections/additions that need to be made to the article.

The dosages of nilotinib being administered are 150 MG and 300 MG of Nilotinib not 150, 200, 300 and 400. The Trial is double blinded with placebo and involves 75 people: 25 at 150, 300 and placebo... Each participant is in one of the three groups and at the end of 12 months will be withdrawn from the drug, go through a 90 day washout period and then be randomly assigned to receive either 150 or 300 MG for one year. The Trial is fully subscribed, will complete in 2020. The reported results are from a preliminary single dosing of Nilotinib that was given to all participants at the beginning of their participation in the trial. Data was gathered from CSF from lumbar punctures taken at randomly assigned times 1-4 hours after drug administration.

This trial is an enhanced trial an earlier trial run at Georgetown University in 2013 (finished and reported in August 2015). The results were very exciting and positively reported in the Press. However, the initial trial was small (11 participants, 7 with PD, 5 with LBD) was not blinded and lacked a placebo.

The deficiencies in the trial were noted by Michael J. Fox's CEO Todd Sherer in an article titled "Separating Hope from Hype". Rather than working collaboratively with Georgetown University, MJFF chose to run their own trial (patterned largely after the GU design).

As far as I can tell, the MJFF is having some trouble getting their trial off the ground. The dispersed research effort (25 locations) is in my opinion fundamentally flawed as there are many research physicians and nurses doing progressive neurological examinations and evaluating biological samples that involve very sophisticated testing. (Like all Clinical Trials for PD, the biometrics are weak). More than that, calls and emails to trial centers in both Phoenix and Boston (both "accepting new participants") were met with "we'll get back to you"... and were never followed up on. So much for the complaint that research is being slowed by the lack of volunteers !

I believe that nilotinib's "garbage collection" of alpha synuclein / inhibition of activity of c-Abl protein make it one of the most promising repurposed drugs for slowing Parkinsons Disease. That's why I'm investing my life and time in this trial.

It will be interesting if this turns out to be a winner drug for PD and MJFF has played a bit part.

[tacato in reply to FMundo]

Very well put FMundo. I am also in the Georgetown study and can confirm the details of the study as described by FMundo.

[parkie13 in reply to FMundo]

Thank you for posting Mary

[SELFMeder in reply to FMundo]

Is there a way we can mimic this study? Can we order the supplement? Did the earlier small study id any risks?

Thank you for sharing.

[MBAnderson in reply to SELFMeder]

SELFmeder, as in do-it-yourself Medicator?

You ask the right questions.

Yes, there is a way we can mimic the study. There are some who are already doing that.

It's not a supplement. It's a chemotherapy drug for Philadelphia positive chronic myeloid leukemia.

I agree with Frank, as things stand, it is perhaps our best hope, but there are 2 problems.

1st, on one hand, the current phase II trial is scheduled to end in October 2020. One year to analyze and publish the results puts it at 2021. One year to organize phase III trials, 2022, which then last until 2025. One year to analyze and publish results 2026 and 2 years for FDA approval, 2028. I’ll be dead by then.

2nd, on the other hand, in the hands of do-it-yourself amateurs like us, unsupervised, it's a dangerous drug.

[jenniferdunstan in reply to SELFMeder]

Excellent question! I would love to know if there's a way to get a jump start on their regimen.

[PixelPaul in reply to FMundo]

Thank you @FMundo, very interesting insight.

[munchybunch in reply to FMundo]

Have you had any side effects?

[FMundo in reply to munchybunch]

No side effects. Remember this is a double blinded test. There is a 33% chance that I'm getting the placebo (no nilotinib)

[jenniferdunstan in reply to FMundo]

Thank you so much for posting this encouraging news. Is there an update available as your post is from a year ago...I'm keen to learn more.

[MBAnderson]

tasignalawsuit.com/?utm_sou...

[FMundo in reply to MBAnderson]

Any comment on your link to lawsuits involving Novartis' Tasigna?

[MBAnderson in reply to FMundo]

Yeah, I have a fair amount to say.

It's one more thing to make me anxious.

For a class-action lawsuit to be underway means the law firm has researched this exhaustively and concluded the harm is real, the frequency is high, and bad faith on the part of Novartis.

The frequency is really, really high, i.e., 25%, but they just call that a "vascular event," so that does not tell us if it's part of the atherosclerosis problem. Some of that could be part of the QT prolongation problem. 16% suffered from peripheral artery disease.

If I were taking the drug under supervision like you are, I'd print this out and bring it into the trial doctors and I'd pay attention to their reaction to see if they knew about it. I would probably also insist that they look for signs and monitor for it.

If you do something like this, please get back to me with what they say. (Vicarious supervision.)

I'm going to begin monitoring/testing for this on a regular basis.

We need to look into this further. Surely for this trial to be conducted in 25 locations, some of these panels who approved the trial would have come across this, so there is something amiss here.

PS. What were the values of your spinal tap?

[MBAnderson in reply to MBAnderson]

I replied via email, but for the benefit of this thread, I agree with your brother and that this law firm is hyping the problem. In order for trial like this to take place in 25 locations, each location has to assess their liability which means it must pass muster with a panel of experts, i.e., oncologists, neurologists, doctors, scientists, hospital/university administration, and government authorities. If the drug were harming 25% or 16% of the population, they never would've made it to phase II trial.

In conclusion, false alarm.

I'm going to keep plugging along.

Marc

[MWLE in reply to MBAnderson]

The use of the drug for cancer is around 800 mg. The use for PD is around 150 mg. There is a significant difference in the amount. Not sure how much the risk is with smaller dosage.

[jeffreyn in reply to MWLE]

According to the PNT article (and also the Lyon "abstract" that the article is based on), it seems to me that 15 participants are taking 400mg nilotinib.

Unless the Lyon abstract is also wrong ...

iaprd-world-congress.com/in...

(4.62 MB PDF - see page 29)

[MBAnderson in reply to jeffreyn]

See FMundo post at the top this thread.

[jeffreyn in reply to MBAnderson]

From the "Results" section of the Lyon abstract:

"Further analysis will be performed to compare plasma and CSF levels of these biomarkers between this single time administration and 52-week treatment."

The way I see it, the only way that they can do this comparison is to continue to give the 4 different doses (150, 200, 300, 400) for a full 52 weeks.

[MBAnderson in reply to jeffreyn]

You may well be right. I don't know. I was just referring you to Frank's post as an FYI because he's in the study. You probably saw the the post below Frank's, from tacato who says he is also in the study and he confirms Frank's description. However, your point makes sense to me.

[MWLE in reply to jeffreyn]

If I recall, the original phase I was using 150 mg. It had significant impact on the patients. I believe the effect dosages may be lower than 150 mg.

[jeffreyn in reply to MWLE]

From the "Conclusion" section of the Lyon abstract:

"Importantly, the dose response of oligomeric alpha-synuclein and HVA changes to nilotinib suggests that the dose administered may depend on the stage of disease to potentially halt PD progression."

I had a bit of trouble understanding this sentence. What I think they are saying is that the stage-of-disease may dictate the appropriate dose of nilotinib to administer. And from what they say earlier in the abstract, an earlier stage-of-disease would seem to dictate a lower dose.

[MBAnderson]

I recently have had a change of heart regarding Nilotinib.

I began taking it 28 months ago November 1, 2016. For a long time I felt it was not doing anything for me, that Pagan and Moussa had exaggerated their claims. I now look back on that as an unrealistic expectation for the dose I was averageing, 150 mg a day.

Through much of 2018 I was reporting that my progression was stabilized or slightly improving, never being certain of which. In anticipation of entering the ENT-01 trial January 30, because I couldn't do a contraindications search on an experimental drug, I discontinued Nilotinib 2 months ago, January 15. Now, over the past few weeks, all my symptoms have clearly worsened. I attributed my stabilization to the sum total of my regimen, but now feel it must've been due primarily to Nilotinib because I've made no other changes.

All of which is to say, I'm quite confident N has been doing me a lot of good and in about a year from now when the current phase II trial is complete, I'm going to begin my quest to find a compounding pharmacy to make some more.

Marc

[jimcaster in reply to MBAnderson]

Marc-

When I read the first sentence of your comment, I feared you had given up on Nilotinib, which discouraged me because it seems to be one of the most promising treatments which may soon (relative term) be available. I'm glad your change of heart is in a positive, optimistic direction. 😊

By the way, it's sunny and 50 degrees in Minnesota according to my car thermometer. More reason for optimism!

[MBAnderson in reply to jimcaster]

Jim,

It's cold here today -- 68°. We come home in early May when it should be about 68° in St. Paul.

Most of the past year, I was taking too small a dose, 125 mg/day. If I were taking 200 mg/day, I would have done even better.

I'm surely not top of every promising therapy, but from what little I know, Nilotinib is the most promising for the primary reason it seems to benefit the largest percent of the cohort, if not everybody who takes it.

1 of the obstacles will be that Novartis may try to get $40,000 per year for it, which will cause a lot of insurance companies to come up with some BS rationale for not covering it -- thereby creating a black-market where a lot of PWP will find ways to have it made themselves.

If it makes it through phase III, it could be on the market 5 or 6 years.