Correlation of individual SMN protein with observed efficacy in the risdiplam SMA clinical trials

<h3></h3> Pharmacokinetic and pharmacodynamic data from risdiplam clinical studies (including infants to adults, with a body weight ≤109kg and aged ≤61 years old) were used to select dosing regimens of 0.2mg/kg for infants aged between 2-months and 2-years, 0.25mg/kg for children ≥2 years old with a body weight &lt;20 kg, and 5mg for patients with a body weight ≥20kg. Here we assess the correlation between individual patient SMN protein level and observed efficacy. Risdiplam’s mode of action was confirmed by the shift from SMN2Δ7 mRNA to full-length mRNA. Risdiplam treatment led to a ≥2-fold median increase in SMN protein levels within 4-weeks of the start of treatment, which was maintained throughout treatment. Exposure–response analyses assessed the correlation between individual SMN protein levels and observed efficacy in pivotal studies with SMA Type 1 (FIREFISH Part 2; NCT02913482) and Types 2/3 SMA (SUNFISH Part 2; NCT02908685). Correlation-efficacy analyses were conducted using absolute SMN protein values during the study treatment period and with the change from baseline in SMN protein level obtained for each patient pre- and post-risdiplam treatment. The results of the correlation of SMN protein in blood versus the assessed efficacy endpoints of the FIREFISH and SUNFISH studies will be presented.