Trofinetide #3

trofinetide1And 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!

 

 

 

 

 

 

 

Advertisements
This entry was posted in boys with Rett syndrome, breakthrough therapy, FDA, hope, margaret brimble, Neuren Pharmaceuticals, NNZ-2566, Orpan Drug Status, orphan drug designation, Rett Syndrome, rettland.org, Trail to a Texas Trial, Trofinetide, Trofinetide Pediatric trial, Trofinetide Phase III, Uncategorized and tagged , , , , , , , . Bookmark the permalink.

17 Responses to Trofinetide #3

  1. Harsh Miglani says:

    Hi, can we expect that medicine will be available in open market by end of 2018 ?
    What will be the price ? I heard it would be too expensive ?

    • melelllan says:

      Since I am a parent and work neither with Neuren nor any of its affiliates (if it has any) nor the FDA nor Rettsyndrome.org I cannot answer that question and I seriously doubt there is definitive answer either as to when available or price. Sorry.

  2. Harsh Miglani says:

    One more query please….can this medicine helps in leading a normal life or just eliminates few symptoms ?

  3. melelllan says:

    The trials have been too short to say with any certainty what the eventual outcome will be. We should have a better idea when the results of the last trial come out. No matter what, it’s unlikely that all the children will have the same response. We have to wait and see.

  4. Rune says:

    I think all of us in the Rett community worldwide are hoping for the best for Neuren. Personally I am convinced that Trofinetide will have a large impact on the lives of our little girls of all ages, and your blog has really been a great joy to me so far.
    From my experiences with clinical trials, I expect that there will be one trial with 6 months of double blinded treatment for each participant followed by an extension trial for some long term safety data with 6 months of open label treatment for each participant wishing to continue.
    I don’t think Neuren will have any trouble finding enough participants, and looking at the data from the two phase II trials, they will not need to go anywhere near 3000 patients to have a rather high power. Don’t expect the phase III trial to have more than 300-500 participants. Half a point on a CGI scale after 6 weeks (usually around that time the placebo effect is at it’s peak), and a tendency toward an increasing gap between placebo and active is a really strong indicator that it works, and that if it works the study will be able to show it with around 500 patients.
    You mention the number of drugs not making it all the way to the market, and that might seem disconcerting to some, but I have seen several drugs fail, and often they don’t have the same amount of positive evidence in phase II as Trofinetide, sometimes they failed in one indication before having some success in another. Trofinetide at least has shown positive signs in two different indications.

    • Harsh Miglani says:

      Is it for fragile x also ?

      • Rune says:

        As melelllan said, there has been a successful trial in Fragile X.
        If Trofinetide is approved by the FDA, I think some doctors in the US will be willing to prescribe it off label to Fragile X patients, especially if a further phase II or III study in Fragile X shows some additional promise.
        If I had anything to do with Neuren, it would probably be illegal for me to even mention the possibility of off label use, and I only mention it at all because the safety profile thus far looks fine for Trofinetide and there is as far as I’m aware no drug for Fragile X, and there is some evidence of it working from a double blinded trial in that indication. Those are probably the only circumstances where I would recommend off label use.
        And of course as a parrent to a disabled time one year of waiting can feel very long, I can’t imagine how it must feel for those who have actually had the drug and have waited for what seems like an eternity.

  5. melelllan says:

    It has had a trial for Fragile X but those trials are not as far along as for Rett syndrome

  6. Harsh Miglani says:

    `Hello, do anyone know the status of the III phase of trial ? and by when this medicine will be available in the market ? because some where I have read that this medicine will be launched in USA market in 2021.

  7. melelllan says:

    I know that Neuren is working on finishing a final toxicity study. I expect that when that is presented to the FDA we’ll here something shortly after. Right now everything is speculation. Though I think that is a reasonable timeframe. Just have to wait.

  8. Father says:

    Good day! Does anyone know how to register to the number of participants of III (third) phase study? I have a daughter, she is 2 years old. Diagnosis : Rett syndrome with hard classical form. We live in Kazakhstan (Central Asia).If anyone know how to be a volunteer to test Trofinetide (3 phase) , help me please! (i have an opportunity to go to the necessary place if needed). Next question is : is there any news about the time of selling of Trofinetide? Thanks for any provided information !!!

    • melelllan says:

      Hello, I’m very sorry to hear about your daughter. The trial specifics have not been released. There is a chance there might be an international site/s but we won’t know until they release that info. I am not sure they will allow such a young child since it’s been tested on 5-45 year old. You can check this site periodically, when the trial starts recruiting all the info will be there. http://Www.clinicaltrials.gov

      We must first get approval by the FDA before it will go to market and that won’t happen until this next phase is complete. I’m sorry it’s not faster.

      • Father says:

        Thanks a lot for your answer!
        Can u advice us, if there are any special drugs from the symptoms (such as hands stereotypes, to develop way of walking and etc.) in the US? any special american vitamins, amino acids or biologically active additives ? the main point is that our (Kazakhstani) doctors don’t know about such disease , that’s why we don’t have any medicines.
        thanks in advance!

  9. melelllan says:

    Hi, it must be very rare there. If you can/are on Facebook there is a site: Rett syndrome family support forum. Many families from all over the world are there to help you! But, just in case- you can contact Rettsyndrome.org and request a CD of the Rett Syndrome handbook. To answer your questions as bedtime can not knowing what is available in your country- for nonprescription medications that some have seen improvement are fish oil for motor and cognition; magnesium for constipation and mood control. As far as hand stereotypes there is no medicine for that, some people put arm brace/s to keep hands out of the mouth and on the less dominate hand side giving their dominate hand a chance to work. Just to let you know nearly half are left handed so that can be the dominate side. There was a study with IGF-1 and some parents so improvement with that, not the kind weight lifters use, it is an injection and a prescription. For walking, many use gait trainers as part of their PT therapy. There is a device that you may be able to purchase called an UPSEE it’s a harness that attaches to the parent and allows the child to mimic the walking of the parent. A very few parents have tried feeding raw fresh placenta either from a newborn sibling or a friends to their children for the stem cells, they believe it has helped, but there is no studies in this. The fish oil did have a study and some children definitely improved. Unfortunately, there are still doctors in America who have never heard of it, too. Here is s link to Rett syndrome Europe, they have good resources, too. https://www.rettsyndrome.eu Also, there are no medications in America specific for Rett syndrome. The most widely recommended is the fish oil. And then each child is treated systematically for their specific issues. If you want to email me (I’m on my phone right now, so not easy to do research for you, ) m3ml@hotmail.com with specific issues I can do research for you and/ or put you in contact with people whose children present with the same issues as your daughter. You will find, if you join the Facebook forum that we are all there to help you, you will get a TON of suggestions, and possibly a family near you. I wish you all the best. It’s not an easy journey. Oh, there are also dad only forums on Facebook, too. Just email me and we can go from there to get you some help.

  10. melelllan says:

    Sorry there are some typos, I hate autocorrect. “Bedtime” was supposed to be “best I” lol sorry😉.

    • Father says:

      Thank you so much that you find a time and gave me very helpful information ! You are very kind and strong person! i wish Katie will get better soon and everything went well!

  11. melelllan says:

    Thank you, the best to you🙂

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google+ photo

You are commenting using your Google+ account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

w

Connecting to %s