All is Not Quiet on the Trofinetide Front #1 A Chess Game

It’s been very quiet in the public eye in regard to Trofinetide. We all are in a holding pattern as we wait for Phase III to begin, but BEHIND the scenes things are progressing strategically and clearly, like a chess game, each move calculated for optimum impact.



What don’t we know yet about Phase III:

  • exact date for Phase III to start
  • the age cutoff
  • the criteria
  • the sites

What DO we know:

  • Phase III will start in the later half of 2019
  • Sites will only be in America
  • It will last about a year
  • Doses will be adjusted for weight in a four tiered system
  • It will include approximately 180 participants
  • will be assisting in reimbursement of travel expenses.
  • The delay in starting the Phase III trial is NOT because of the partnership with Acadia (the North American company that Neuren has partnered with to get the Phase III done and Trofinetide to market)

But, we’ve know all this for awhile.

What has BEEN happening since the Phase II wonderful, outstanding results?? And WHY is everything taking so long?? There are two major “fronts” (in my opinion) in this battle to get Trofinetide to our children- The FDA and the financial/logistical aspects. Today we’ll discuss the FDA, it’s by far more straightforward.

The FDA is a government agency. Let’s be honest, when does the government do anything as fast as we would like? Ok, that’s a little facetious, but sort of true. We do, however, have to keep in mind we damn sure want this to be done perfectly because it would really suck if at the end the FDA goes “oops, um, this part here wasn’t conducted properly” and we have to go through it all over again. To that end, Neuren and the FDA conducted an “End of Phase II Meeting” in October of 2017.  This addressed key issues of the Phase III. I know, you’re asking yourselves-that was 2 years ago! What’s taking so long then?

In June 2018, the Chairman’s Address at Neuren’s annual stockholders’ meeting went over some of the conditions the FDA placed on Neuren in order to prepare for Phase III. Two of the most time consuming conditions have been-

  • “In preparation for the Phase 3 trial, which will involve a longer duration of treatment than the Phase 2, there is a standard requirement to generate additional data from non-clinical studies in two species. We previously completed one of the studies and the second is currently in progress. The second study, which will conclude in Q4 2018 has two components and I am pleased to report that both components are on schedule, with no unexpected findings to date.”
  • Manufacturing is a key element of the preparation for Phase 3. A Phase 3 trial has to be conducted using the commercial (“to-be-marketed”) product, which means that changes to the Phase 2 product supply arrangements and a significant investment have been required for manufacturing of both the drug substance and the finished drug product liquid formulation and packaging.

It is the second condition that has really been the driving force behind how soon/late the Phase III trial starts. You can read more about it in the link above. However, we can all see by the first requirement alone, having most likely just finished, the Phase III could not have started until 2019. This data needs to be given to the FDA and has to be signed off on.

The second condition is something I will go into more in the next blog post. For new parents and for those who may need a refresher- Trofinetide is targeting the underlying biological cause of Rett syndrome and doesn’t treat any singular or particular set of symptoms. It’s had two very successful Phase II trials (one adult, one pediatric); it is well tolerated with no safety concerns identified. If you’re interested in a breakdown of the Phase IIb (pediatric) results, you can look back at my previous posts on the results. 

A quick visual for new parents who might be wondering what Trofinetide actually does.

In the brain, neurons have dendrites. Dendrites act as telephone wires. Between each one is a miniscule distance the signal has to jump, this is called the synaptic space. In the normal brain there are multiple dendrites on each side of a neuron to send out and receive instructions. In the Rett brain, the dendrites are both too few and too short. This means that while the brain is sending out the correct signals, the synaptic space is too vast and the signal gets lost in the space between.

Take your hands and spread the fingers out until they are almost touching-this is the normal neuron/dendrite with a very small synaptic space; now close your fists-this is the Rett neuron with a huge synaptic space. Now, open your hands again with the fingers almost touching-this is what Trofinetide does, regrows the dendrites to the correct number and length, allowing the brain’s signals to get to where they need to go.

I cannot end this segment without discussing Margaret Brimble, the Mother of Trofinetide, because we all owe her such a debt. Recently made a Dame, Dame Brimble has also been given the high honor of “Fellow of the Royal Society.” Without her own passion for discovering new drugs to treat a variety of conditions, we would not be on the cusp of, at the very least, a small victory against Rett syndrome, though I believe it will be a much bigger victory than anticipated.

In ending, I know it’s hard to wait and it seems like things are taking for ever, but everyday we get closer to a definitive endpoint, not some “if” hanging over our heads. It’s going to happen; it’s going to be a game changer for all those who participate and for all those who have to wait for it to get to market. It’s a given, that each child will have a somewhat different response, as true with all medications, but it is my fundamental belief that all children will respond positively in some way. Hang on, we’re almost there.


This entry was posted in Acadia, anxiety in Rett syndrome, Ataxia, boys with Rett syndrome, breakthrough therapy, Communication, cure, FDA, Fragile X, hope, margaret brimble, Neuren Pharmaceuticals, Rett Research, Rett Syndrome,,, Trail to a Texas Trial, Trofinetide, Trofinetide Pediatric trial, Trofinetide Phase III, Trofinitide, Uncategorized and tagged , , , , , , , , , , , , , , , , , , , , , . Bookmark the permalink.

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