And on we go! So far I’ve discussed what Trofinetide is, how it came about and what it does. Great, but what are we talking for a timeline, right? Who holds the strings? Just what the heck are the steps to get it to our kids! Note: This is pretty lengthy and may be boring to some, but I thought it important to put how long we all feel it is taking into perspective with how long it could take!
Well, some of those steps are already completed. There was an initial trial, Phase I, of a very small number of adults, I think it was 10, to make sure the drug was safe. It was very short, you can read about it here. That was completed in 2012.
Next came Phase II. This was begun in 2013 and completed in 2014. This was a much larger study, with 53 participants ages 16-45 (Katelin was participant #26 and was either the last or next to last to receive the lower dose of 35mg/kg or placebo; the higher dose was 70mg/kg) You can read about this phase here.
In between these two phases, something very important happened. Neuren Pharmaceuticals was granted “Fast Tracked” status for NNZ-2566 (later named Trofinetide) So, what’s the big deal about that? Quite a bit, actually. The FDA can grant Fast Track status to a drug that is developed to meet an unmet need for a serious illness/condition. There are multiple advantages in having been given Fast Track status-
From the FDA website:
A drug that receives Fast Track designation is eligible for some or all of the following:
- More frequent meetings with FDA to discuss the drug’s development plan and ensure collection of appropriate data needed to support drug approval
- More frequent written communication from FDA about such things as the design of the proposed clinical trials and use of biomarkers
- Eligibility for Accelerated Approval and Priority Review, if relevant criteria are met
- Rolling Review, which means that a drug company can submit completed sections of its Biologic License Application (BLA) or New Drug Application (NDA) for review by FDA, rather than waiting until every section of the NDA is completed before the entire application can be reviewed. BLA or NDA review usually does not begin until the drug company has submitted the entire application to the FDA
The end result being: The frequency of communication assures that questions and issues are resolved quickly, often leading to earlier drug approval and access by patients.
As you can see, this is a fantastic designation. However, there is also another designation that NNZ-2566 was given in 2015-Orphan Drug Status. While this doesn’t directly affect the timeline, it gives great incentives for companies to continue the development and trials necessary to get the drug to market. Without these incentives, it becomes more likely that a company would not see the possible profitability as a reasonable risk. Trofinetide has also been granted Orphan Drug status by the European Medicines Agency (EMA).
There is a third designation- Breakthrough Therapy status- that Trofinetide did not receive, though Neuren applied. You can read all about my thoughts on that, here. If we were in person, talking face to face, you and I, I would have to say “don’t get me started on Breakthrough Therapy status!”
In the end, though, being Fast Tracked is the main thing. So, you ask- it’s taking FOREVER, it doesn’t seem very quick to me! But, really it is. It’s been only 6 years from the time of the first phase. We are now looking at, very shortly, the third and final phase. If you were to look at the FDA’s website about clinical trials you would be aghast at how long and how many participants are generally included.
FDA: Phase I: Study Participants: 20 to 100 healthy volunteers or people with the disease/condition.
Length of Study: Several months (approx. 70% of drugs move on to next phase)
NNZ-2566: Study Participants:10 Length 5 days
FDA: Phase II: Up to several hundred people with the disease/condition.
Length of Study: Several months to 2 years (approximately 33% move on to next phase)
NNZ-2566: 53 participants Length: 6 weeks/participant; Phase IIb (Pediatric phase) 82 participants Length: 11 weeks/participant; less than one year each, overall
FDA: Phase III Study Participants: 300 to 3,000 volunteers who have the disease or condition
Length of Study: 1 to 4 years (25%-30%) move forward.
Trofinetide: Phase III; I haven’t heard anything yet about how MANY participants there needs to be, but from everything I’ve read and heard about the trial will be 6 months/participant; less than one year overall.
Now, if Rett syndrome trials had the same guidelines applied it would feel like eons! Imagine getting several hundred participants just for the Phase II! and 3,000??? never. And look at the percentages that progress! Say 100 drugs start out in Phase I, 70 move on to Phase II, only 33% of 70 move on; that’s approx. 23. What happens after Phase III? only 25-30% of those 23 move on; that’s approx. 6. Now, there’s no doubt in my mind that Trofinetide will be one of those 6, but really it’s beating tremendous odds here, both in timeframes and probability.
Ultimately, the FDA holds the strings. Luckily, with Fast Track status, any questions/problems/concerns can be addressed while this third trial is ongoing, without it Neuren could get to the end of the trial and the FDA goes “oops, we don’t like the way you did this, do it all over.”
Fairly soon the call will go out for participants. Hopefully, there will be enough sites open in the States and abroad to fill all the necessary spots quickly. Let’s do it, folks. Rettland.org is there to help with expenses; I for one will open my home to any family if they have a site in LA and/or San Diego (which would be a bit of a drive, but I have a pool and hot tub 😉 ) We can do this!