In this presentation, Dr Craig Erickson (Cincinnati Children’s Hospital and Chair, FXCRC Clinical Trials Committee) discusses the mechanism of action of trofinetide (NNZ-2566, Neuren Pharmaceuticals) and its potential suitability as a treatment for Fragile X syndrome.

Trofinetide is a synthetic analogue of a molecule derived from IGF-1 (Insulin-Like Growth Factor), a growth factor produced by both the major types of brain cells: glia and neurons. IGF-1 in the brain is critical for normal brain development and for responding to injury and disease.

Additional Q&A

After the webinar, we asked Neuren Pharmaceuticals to answer some of the most pertinent questions about trofinetide, which we share with you here:

Will girls be included?

We have no plans to include females in this study.

When the results will be known?

It is anticipated top line results will be available before the end of 2015.

How many people does the trial target to include? How many people are included so far?

The study is targeted to include 60 subjects. We remain on track with enrollment.

Will there be extensions?

There are no planned extensions in this study. A Phase 2 study of this kind is a necessary precursor to larger studies where open label extensions may be appropriate and studies in younger individuals. These larger studies must also be completed before the drug could be approved by the FDA and available to consumers.

When would approval of the drug (if it works) happen?

Larger studies and studies in younger individuals will be needed to demonstrate the required level of safety and efficacy before the drug could be approved and available to patients. These studies and their planning, execution and analysis take time and resources. The quicker that Neuren can complete the ongoing studies, the sooner those large scale studies can commence. Neuren has two special designations from the FDA for our development of NNZ-2566 in Fragile X: Fast Track Designation and Orphan Drug Designation. Fast Track designation can expedite the development and review of important new medicines that are intended to treat serious diseases and fill unmet medical needs. Orphan Drug designation is a special status that the FDA may grant to a drug to treat a rare disease or condition that can help in ultimately making the drug available commercially to families. Both designations are important milestones in accelerating the development of viable treatments for Fragile X, and demonstrate a recognition of the critical unmet needs of individuals with Fragile X.

Why only males?

Fragile X syndrome (FXS) is caused by mutation of the FMR1 gene on the X chromosome. When the gene mutates, it switches off production of a protein (FMRP) that is involved in brain development and other functions. Females have two X-chromosomes so any mutation or deletion in one of these FMR1 genes is potentially compensated for by having a second, viable copy on the other X-chromosome. Males have only a single X-chromosome, hence they are generally affected with greater severity. As a result, any changes in the sign and symptoms of Fragile X in males during the study can more easily be attributed to a treatment benefit rather than the presence of a functioning FMR1 gene.