Jimmy,
Happy to elaborate a bit.
First a refresher from Phase 2a and Phase 2b for both Retts and Fragile X trails.
P2 (names changed or redacted)
III. EXCELLENT NEWS/UPDATE: Steve saw his tutor this morning and she saw a TON of differences- fluent speech, reading without skipping words/without scrambling words/without rushing to get through, really good eye contact, problem solving, novel ideas, faster processing, self-regulation, better imitating! Even two of her neighbours noticed that something was different in a brief interaction with him. Not only was he not constantly talking, perseverating or flapping, he was listening, answering and not interrupting!!!! Everyone saw a different kid!!
IV. And tonight, when we brought out a City Lego City Garage (age 6-12) to assemble, it was not me assembling it. He had to be prompted to look at the picture now and then but he basically burned through it. Every other time he got impatient and frustrated and it was always me building them. It's going to be very sad getting off this drug by the end of February. I do have a different kid and I'm remembering that ease of parenting that I experienced during the 3 and 1/2 years of arbaclofen. He has been on this drug for only 3 days.
V. Here is a short clip of how Steven’s temper is tempered by this Neuren trial drug. Snaps right back. No meltdown or long lasting effects. [link removed].
VI. More updates: Motor Skills- Steven does not have trouble negotiating unshovelled snow or other barriers! He moves differently! School doesn't see it because there's probably too much going on BUT his OT wrote me and said, " Tuesday I noticed some nice changes in Steven. He said " I want to tell you what I did yesterday." And proceeded to tell me he went to Tom’s. He was also willing to work harder and try a new activity with me in the lycra... It was pretty awesome!"
VII. His calmness is noticeable. No freakouts, no meltdowns, no getting upset at all! He thinks, has better conversations, listens, answers....
VIII. This drug is good!
IX. Parent 2: I noticed many of the same changes in Blair when he did it. X. So what do you think about this?? Instead of asking (or telling) me "no music" in the car, he is listening to jazz and blues on the radio with me and he is requesting it! And again, was out with him at night at a busy restaurant yesterday. He walks right by (both for entering and when we're done) crowded areas filled with families with kids. He's looking around, continuing his conversation with my friend, still walking smoothly. In the past, he would have panicked and been loud, awkward, covering his eyes and stumbling around and basically, pushing to get out. Lastly, funny Steven- he wakes me up this morning, asks me for orange juice while he turns on the TV in my room. Me: "I can't believe I have to hear this show (Super Why) first thing in the morning". Steven says, "well if you go downstairs, you won't have to hear it". XI. Last day of dosing will be February 9. We will miss this drug.
XII. Last post on the effects of NNZ-2566 (the Neuren trial drug)- Okay, you may know we had a blizzard and I've been shoveling on and off for over 24 hours. Again, not only is Steven as cool as a cucumber about most everything but he moves through un-plowed, unshoveled snow like a typical kid, not only not freaking out or not being able to physically negotiate an uneven terrain but he does it, gets from a to b without a peep other than calm comments like "this is a mess!" This attitude and capability is another thing I remember from the arbaclofen trial which he was in for 3 and 1/2 years- he is unencumbered and free to be relaxed and me? I am a better, more honest parent. He's a teenager so I don't know how much he's just putting up with, but I talk to him, not just circumvent potential disasters, not be on edge. If I don't like something, I tell him. There is not going to be a backlash or an upset. I LOVE this medicine. I love my kid more too.
XIII. When he's done and off this drug. I am not going to try the Alcobra drug. I am not returning to Acamprosate because he would talk non-stop. He will try minocycline again and if that's a failure, we may go back to acamprosate. Don't know what else to do right now. XIV. He's been off the drug since last Monday. He gags again at smells, is still relaxed but not as relaxed. OCD and perseverative talk back to a degree. Moving a little jerkily again.
Following the posting of the above across various social media platforms, the P2 trials all met their primary end-point of safety and tolerability with strong efficacy signals.
Results corroborate the positive pattern of clinical benefit of trofinetide in improving core symptoms of the disease similar (across both Rett and Fragile X).
The improvement was observed both in the clinician as well as caregiver (parent) assessments.
While some immediate improvement was evident, the extent of the improvement relative to baseline progressed, especially from around the 4 weeks mark, and even continued after the drug was stopped (disease modifying potentially).
P3 Lilac and LavenderUnfortunately as required the company has tightened its enforcement of confidentiality and reporting of Ph3 results on SM (as reasonably required) However, here is an example of some of the P3 anecdotal I have collected thus far:
Parent 1:
"We really thought XXXwas on the placebo, but then week 4 she started walking down the stairs along and getting into and out of my mini van. XXX does still gain skills normally so idk if we got the medicine or it's coincidence"
Parent 2 on open label trial after noticing no change during blinded trial:
"Since XXX has been receiving her trial mediciation we have notived some changes..she's more engaged, her motor skills are improving and her eye contact is amazing! The best part is we are only 4 weeks in!"
Parent 3:
"Brilliant news, I was unconvinced despite promising phase 2 results and a couple of rett parents singing its praises no end.
Having seen its affects first hand in some of the girls in the phase 3 trial it can't come quick enough so anything that can give it that helping hand through the red tape is most welcomed"
"improved motor function, things children haven't done in years, bear weight, steps, hand to mouth feeding. Word in a couple of cases. We aren't talking a cure but some good smaller improvements that can help their qol."
Concluding comments:From firm KMR Group, the following shows the probability of success of trials.
Phase 2 — 22% (Trofinetide has passed 4 of these!)
Phase 3 — 65%
In short, we have passed the highest risk stage 4 times (Phase 2a and 2b for Retts and Fragile X) and the 65% is probably conservative as it assumes (incorrectly) all therapeutic areas, drugs (marginal versus strong early results), trial designs (objective versus subjective measures) and teams (proven commercialisation/regulatory experience) actually have the same probability of success.
So if you adjust based on the molecule size and indications being tested, we are probably sitting at 75% chance of a rerate to say $10.
Not without risk, just as with any trial, but the RvR is attractive here to include within a diversified portfolio.
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