Exondys 51: how was the first human dose set?

The public FDA and EMA reviews of Exondys 51 don't say how the first human dose was chosen. That rationale is in the IND, which is confidential, so it is missing for most approved products.

Find the highest dose with no adverse effects (NOAEL) in each animal species, convert it to a human equivalent dose, usually by body surface area, pick the most appropriate species, then divide by a safety factor (default 10) to get the maximum recommended starting dose.

NOAEL / key findings: Kidney tubular degeneration in all species; monkey NOAEL 320 mg/kg (~20x AUC); juvenile rat NOAEL 300 mg/kg (6x); bone density loss (FDA pharmacology/toxicology review, p. 91)

Full method, every step sourced →