Bioequivalence and food effect assessment for a new risdiplam tablet formulation in healthy volunteers


Clinical Trials

Poster Number: S109


Heidemarie Kletzl, PhD, F. Hoffmann-La Roche Ltd, Katja Heinig, F. Hoffmann-La Roche Ltd, Birgit Jaber, MSc, F. Hoffmann-La Roche Ltd, Wai Yin Yeung, PhD, Roche Products Ltd, Hugh Coleman, Fortrea (formerly Covance), Barbara Lomeli, Fortrea (formerly Covance), Lydia Buckley, Fortrea (formerly Covance), Alice Varghese, Fortrea (formerly Covance)


Risdiplam (EVRYSDI®) is an oral survival of motor neuron 2 pre-mRNA splicing modifier approved for the treatment of spinal muscular atrophy.

The approved risdiplam dose for patients with a body weight ≥20 kg is 5 mg. The commercially available formulation is an oral solution that is drawn up in a syringe by the patient or their caregiver every day. A bioequivalent tablet formulation would provide patients weighing ≥20 kg with the option of replacing the current oral solution with the simpler daily administration of either swallowing a tablet or dispersing it in water and drinking the suspension.


Part 1 of this healthy volunteer study (NCT04718181) assessed the relative oral bioavailability of, and the effects of food and stomach pH on, two new risdiplam tablet formulations. Here we present the results from Part 2 of the study, which assessed the bioequivalence and food effect of the most promising tablet formulation from Part 1 versus the currently approved oral risdiplam solution. Using a four-way crossover design, each volunteer randomly received a single dose of 5 mg risdiplam oral solution in both fed and fasted states, and a single 5 mg risdiplam tablet (either swallowed whole or dispersed in water, depending on their group allocation) in both fed and fasted states.


The new risdiplam 5 mg tablet formulation was shown to be bioequivalent to the current commercially available oral solution of risdiplam, based on the pharmacokinetic parameters area under the concentration-time curve and maximum concentration. In addition, no relevant impact of food on the exposure of risdiplam for either the oral solution or the tablet was found.


The new risdiplam tablet formulation will provide a convenient alternative to the approved oral solution for patients taking the 5 mg dose of risdiplam. Additionally, administration of the oral solution or the tablet is not affected by whether individuals are in a fed or fasted state.