Roche presented data from its risdiplam pivotal FIREFISH and SUNFISH studies at the 2019 American Academy of Neurology annual conference
31 May 2019
Risdiplam is an orally administered small molecule which encourages the SMN2 “back-up gene” to produce functional SMN protein.
SMA Type 1 trial – FIREFISH
FIREFISH is a trial of risdiplam on 21 infants with SMA Type 1 , in two phases:
Part 1: The aim of the first part of this study is to find the optimum dose to administer. Infants with SMA Type 1 survived and achieved key motor milestones after 1 year of treatment, beyond those expected in the natural history of the condition.
Part 2: In this part of the study, the infants are receiving the dose of risdiplam determined in part 1. Enrollment for this study is now complete and preliminary results are expected in early 2020.
SMA Types 2 or 3 – SUNFISH
SUNFISH is a trial of risdiplam in 51 people with SMA aged from 2 to 25 years, also conducted in two parts:
Part 1: New data from this dose-finding study of SUNFISH reinforce risdiplam as a promising investigational therapy for people with SMA Types 2 or 3 and no treatment-related safety findings leading to withdrawal were seen to date. The functional status of the participants ranged from individuals unable to sit to those capable of walking. Scoliosis ranged from none to severe. As previously reported, a sustained increase in SMN protein greater than two-fold, as measured in blood, was seen after 12 months of treatment with risdiplam.
Motor function was assessed: Among the patients for which the motor assessments have been completed at all visits up to month 12 (n=43), 58% saw an improvement of at least 3 points on the scale from baseline, including 71% among patients 2-11 years old and 42% aged 12-25 years.
While Part 1 of the SUNFISH study was not designed or powered to detect efficacy, the change from baseline in total functional score is the primary efficacy endpoint in the ongoing Part 2 of the trial. To date there have been no treatment-related safety findings leading to withdrawal from any study.
Part 2: Among the infants who received the dose selected from part 1 of the study, 41.2% were able to sit without support for at least 5 seconds. In addition, 11 (64.7%) infants were able to sit (with or without support) while 9 (52.9%) achieved upright head control after 12 months of treatment. Finally, 1 infant (5.9%) achieved the milestone of standing (supports weight) by this 12-month time point.
Roche is planning to include the new data presented at the AAN Annual Meeting in regulatory filings with the European Medicines Agency during the second half of 2019.