Nilotinib

[Sane1]

Nilotinib. Not quite over yet.

medpagetoday.org/neurology/...

[jeffreyn]

See also this interview with Charbel Moussa (30 minute JAMA podcast). It seems to me that he is keen to proceed with a Phase 3 clinical trial of nilotinib for PD.

edhub.ama-assn.org/jn-learn...

[Sane1 in reply to jeffreyn]

Thank you for posting this. I personally found his interview to be informative and honest. I find looking at Abl tyrosine kinase inhibitors and autophagy in PD important. I am looking forward to the results of the phase 3 study.

[sharoncrayn]

He must be living in La-La Land if he feels a Phase 3 is going to prove anything different than this Phase 2. In fact, the results could be even worse.

My advice: Just shut this whole sham down and admit it is a drug that is irrelevant for PD. In fact, it is dangerous under almost any condition.

Another "paycheck" trial, or ego trip...take your pick.

Sharon

[Sane1 in reply to sharoncrayn]

If it crosses the BBB and the neuro pathways are beneficial and safety with lower dosing is being closely investigated I don’t see a downside.

They learned new information about the workings of PD in the “failed “ phase 2 trial that will help with other PD research.

[MBAnderson in reply to Sane1]

Can you remember if Moussa's word choice indicated it was safe or was he more precise saying, 'it was safe in the cohort we tested' because they use pretty severe screening to dis-allow people in the cohort, i.e., anyone with the whiff of a heart condition was eliminated, which is not the general population?

[Sane1 in reply to MBAnderson]

It sounded to me like he was stressing that the safety issue needs more testing especially the lower doses. He did seem to imply that study set up needed to be done differently.

[Dogmatic377 in reply to Sane1]

During the MJFF Webinar of December 17, 2019 the MJFF sponsored trial proponents claimed that only 1% of the drug crossed the blood brain barrier which was insufficient to have any impact on cleaning up the alpha-synuclein. So they feel that this drug cannot be effective.

Dogmatic

[WinnieThePoo]

Dead in the water. Bydureon is still labouring to get a phase 3 under way and had far more positive results

[MBAnderson]

When taking into consideration the history of the trials and the history between MJFF and Georgetown and the claimed issues MJFF raised (flawed study protocols) and considering MJFF has no skin in the game and Moussa does and, lastly, I feel MJFF has more to lose (if Moussa gets it wrong, Moussa is hurt, not the whole of Georgetown whereas if MJFF gets it wrong (Nilotinib proves safe and effective,) MJFF goes down. So, when added to the safety concerns, I stopped taking it.

If it proves safe and effective, I'll start up again.

[Sane1]

I hope nobody goes down. That said

I wouldn’t consider taking it myself until these trials are over and have proven the drug safe and disease modifying.

[Sane1]

If they find it safe I would hope the y wouldn’t have to be any more complicated than most other drugs. We must have the same neurologist lol. Sadly I can’t imagine my neuro following up with lab work. He may ask me if I have had chest or abdominal pain or swollen ankles. I’m sure he would refer me to my general physician if I ever said yes.

[jeffreyn]

Both of the nilotinib Phase 2 trials (MJFF et al. and GU) used doses of 150mg and 300mg (I think that Tasigna only comes in 150mg and 200mg capsules). My understanding of the GU trial results is that the patients on 150mg did better than the patients on 300mg.

If GU do manage to get sponsors for a Phase 3 trial, I hope they include some smaller doses. Perhaps they could try 50mg, 100mg, 150mg and 200mg.

[Sane1 in reply to jeffreyn]

One article I read said that the optimal dose they tried was 200 mg. Don’t think they will go below 159 mg.

[jeffreyn in reply to Sane1]

The only mention I've seen of a dose of 200mg was in an abstract of a one-day trial GU conducted at the beginning of their Phase 2 trial, where they divided the 75 patients into 5 groups (placebo, 150mg, 200mg, 300mg, 400mg). In the results section they stated that ".. lower dose (150mg and 200mg) resulted in a significant decrease of oligomeric:total CSF alpha-synuclein."

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

(4.62 MB PDF - see page 29)

[Sane1 in reply to jeffreyn]

I meant below 150. Good read. It wasn't this article. Have to look for it.

[jeffreyn in reply to Sane1]

I think I've found it. It's the same study, but the full paper, rather than just an abstract:

ncbi.nlm.nih.gov/pmc/articl...

(and the abstract has been re-written)

[jeffreyn]

See also the section on c-Abl inhibitors in Simon's recent SoPD post:

scienceofparkinsons.com/202...

[Sane1 in reply to jeffreyn]

Thank you so much for the link. Lots of interesting research there.

[PDGal4]

I qualified for the trial but chose not to participate. Dr. Pagan at Georgetown said he believed 200 mg would be the ideal dose. I don’t believe it’s available at that dosage, just 150 or 300 mg. Having said that, I know one trial participant who did very well, much improvement also documented by participant’s PT. It’s a shame this has become political.