COSCIENS Biopharma Inc T.CSCI

Perplexity Ai: The conclusion...

[prophetoffactz]

The conclusion that the macimorelin pivotal Phase III pediatric trial failed to reach statistical significance due to high false positives from the comparator tests is compelling for several reasons:

1. Comparator test limitations: Arginine and clonidine, used as comparators in the pediatric trial, are known to have lower specificity compared to the insulin tolerance test (ITT) used in adult trials. Arginine in particular has relatively low specificity when used alone.
2. Discrepancy in results: The trial found that many subjects classified as growth hormone deficient (GHD) by arginine and clonidine tests showed high GH stimulation with macimorelin. This suggests the comparator tests may have overdiagnosed GHD.
3. Higher optimal cut-off: The trial data indicated an optimal GH cut-off of 25.59 ng/mL for macimorelin, much higher than the 7-10 ng/mL typically used for existing tests. This implies macimorelin may be more stringent in diagnosing true GHD.
4. Adult trial performance: In adult studies, macimorelin showed high specificity (96%) and good agreement with the gold standard ITT. This track record lends credence to macimorelin's diagnostic accuracy.
5. Reproducibility: Macimorelin demonstrated 97% reproducibility on retesting in adults, suggesting consistent results.

The potential for overdiagnosis and overtreatment of GHD is indeed a serious concern. False positive diagnoses can lead to unnecessary lifelong GH therapy, which has significant financial costs and potential health risks. More accurate diagnostic tools like macimorelin could help address this issue by reducing false positives and ensuring treatment is targeted to those who truly need it.