Q/A notes from SVBLeerink CC
The QA session seemed to be the most interesting part of the call to me. Thought I would share this with the board. I think the host asked more questions than most hosts, and they were of good quality. I think some of the Qs came from the audience. Lots of interesting comments on Trofinetide. Also, the first question, I think, shows the line Dr.Missling must walk, trying to deal with multiple agencies, and resolve any agency issues to the satisfaction of the other agencies (that are not really involved in the trial)!
(These notes are not exact quotes, but should be the intent.)
Q. The FDA agreed ahead of time to the Avatar endpoint change, correct?
A. Let me use correct language, the Avatar study was done in UK and AUS, so these regulatory agencies approved the changes BEFORE the trial completed. The FDA was not involved in that study, just the US phase 2 study.
Q. Talk about the biomarkers that give you confidence.
A. Not only was S1, which is a biomarker of the drug changed significantly, correlating with the outcome. But also biomarkers of the disease, like seizures having low GABA and to high glutamate, and we were able to show that our drug reverses that. That is important because it addresses not only Rett syndrome, but also other diseases which we are going to address like FragileX. And when you look at LAAA, expressed in many degenerative diseases like Alzheimers and Parkinsons, we were able to reduce that. Thats important, because it shows that something biological is taking place that is beneficial to the system.
Q. And Gaba?
A. Yes Gaba deficiency is known to be associated with seizures, so we were able to show that increasing Gaba reduced the seizures.
Q. Thoughts on Trofinetide?
A. Looking at the Trofinetide study we were actually called from investigators and Rett family members, we were pointed out that just looking at the adverse event profile that there was high prevalence of vomitting(20%) and diahrea(80%). This is very inconvenient for girls that are bedridden or in wheelchairs. That is certainly a manifestation of the drug. We had none of that.
Q. Ref. the Rett program, when is the last time you talked with the FDA, and what is going to be needed to get that approved for Rett in US?
A. I repeat, we shared the US P2 data with the FDA, we need to write the Avatar clinical study report for the FDA but we are sharing this data with the FDA,
then we will discuss the next steps.
Q. That should happen soon?
A. Yes of course we want to move ahead.
Q. Comments on the ongoing trials in general and timelines.
A. Covid is having an effect on trials, but Alz is already fully enrolled, covid is only affecting Exellence.
I also want to point out we are happy to have two independent trials with improvements in Rett adults. Most trials target adolescents as they have better chance of responding. We are fortunate to have good results with patients up to 40 years old. This was not the case with Trofinetide, which didnt see any effect in adults. So it gives us extra confidence in the Excellence study.
