And this is just a follow up on MRI with regards to its use and the FDAs Advice
This is the the review from the FDA on the Duvyzat trial
6.3.2. MRS Biomarker Data as Confirmatory Evidence of Effectiveness
Issue
Determine if the MRS Biomarker Data is adequate to contribute to confirmatory evidence, along
with the single adequate and well-controlled Study 48, to provide substantial evidence of
effectiveness of a treatment benefit of givinostat in patients with DMD.
Background
Repetitive muscle damage in DMD patients leads to muscle fiber death with replacement by fat
and connective tissues. Fat infiltration in the vastus lateralis muscle of the thigh is considered as
a characteristic of disease progression in patients with DMD (Barnard et al. 2020). Vastus
lateralis muscle fat fraction has been shown to be closely related to functional performance and
predictive of functional decline in published studies (Forbes et al. 2014; Mankodi et al. 2016;
Kim et al. 2023)
There is an observed difference in fat fraction as measured by MRS between givinostat and the
placebo in Study 48. The Applicant has proposed this difference as one piece of evidence to
provide confirmatory evidence of efficacy.
The biomarker results were fully analyzed by the
clinical pharmacology review team. The MR imaging techniques were also reviewed by Dr.
Daniel Krainak from the Center for Devices and Radiological Health (CDRH).
Assessment
In Study 48, VL MFF (expressed as a percentage) was included as one of secondary endpoints to
assess the efficacy of givinostat, which was measured by MRS at baseline, Week 48, and EOS
(approximately at Month 18). The longitudinal change of VL MFF for subjects in the Target
population is presented in Figure 10. The observed VL MFF and the change from baseline for
subjects in the target population taking givinostat and placebo are summarized in Table 30.
ConclusionIn conclusion, the increase of VL( Vastus Laterals ) MFF (Muscle Fat Fraction ) from baseline in the
subjects treated with givinostat was found to be smaller than the placebo group, and VL MFF change from baseline is associated with the key efficacy endpoints (4SC, 6MWD and Total NSAA).
The VL MFF data from Study 48 demonstrate a pharmacodynamic effect on the muscle
indicating that the drug is having the intended target engagement resulting in downstream benefit to the muscle.
This pharmacodynamic evidence is capable of contributing to the confirmatory evidence ofeffectiveness of givinostat in patients with DMD.Reference ID: 5351242
PLEASE NOTE :
This pharmacodynamic evidence is capable of contributing to the confirmatory evidence ofeffectiveness of givinostat in patients with DMD.
Unfortunately we didnt get this opportunity
WHY
Were our funds wasted on this trial, we have evidence of hitting our target marker, but either way good or bad we have no
pharmacodynamic evidence as to if it had effect in any way shape or form
See Doc Duvyzats FDA review Doc
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2024/217865Orig1s000IntegratedR.pdf
drug failure i can accept
The UNKNOWN is JUST THAT
UNKNOWN
and he talks about not throwing the baby out with the bathwater
And looking for something in the drug
Wouldnt have had to do that if MRI had been included results would have been front and centre V placebo
Huge opportunity missed to see the method of action our drug may have had in these boys be it something or nothing
Now we will now never know
