Risdiplam Demonstrates Significant Motor Milestones in Infants with Type 1 SMA


In addition to increased motor milestone achievement, the safety profile of risdiplam was consistent with that observed in previous studies, with no new safety signals identified.

Levi Galloway, MD, PhD

Levi Galloway, MD, PhD

Genentech announced its investigational, orally administered survival motor neuron-2 (SMN2) splicing modifier, risdiplam, met the primary end point in the FIREFISH (NCT02913482) part 2 clinical study by demonstrating a significant increase in achieved motor milestones in infants with Type 1 spinal muscular atrophy (SMA) aged 1 to 7 months after 12 months of treatment.

Using the Gross Motor Scale of the Bayley Scales of Infant and Toddler Development Third Edition (BSID-III), 12 infants (29%) sat without support for 5 seconds by the end of month 12, a milestone typically not reached in the natural history of Type 1 SMA (P <.0001). The full cohort for part 2 included 41 infants.

The data, which were accepted for presentation to the American Academy of Neurology (AAN) 2020 Annual Meeting, showed that 18 (43.9%) infants were able to hold their head upright, 13 (31.7%) were able to roll to the side, and 2 (4.9%) were able to stand with support, as measured by the Hammersmith Infant Neurological Examination 2 (HINE-2). A maintained ability to swallow at 12 months was observed in 36 (95%) patients, while 34 (89%) were able to feed orally.

“These results confirm the clinically meaningful efficacy of risdiplam in infants with an advanced and difficult-to-treat disease,” Levi Garraway, MD, PhD, chief medical officer, and head, Global Product Development, Genentech, said in a statement.

READ MORE: High-Dose Nusinersen Trial Paves the Way for More Individualized Treatment of SMA

The median duration of treatment for infants within the study was 15.2 months, and their median age was 20.7 months. Among the 41 infants included, 38 (93%) were alive and 35 (85.4%) were event-free at the time of analysis. Death occurred in 3 infants 3 months into the treatment period, but it was determined to have no correlation with risdiplam treatment.

A Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) score increase of ≥4 points was reported in 37 (90%) patients, with 23 (56%) of them achieving a score above 40.

Safety for risdiplam in the FIREFISH study was consistent with its known safety profile, with upper respiratory tract infection (46.3%), pneumonia (39%), pyrexia (39%), constipation (19.5%), nasopharyngitis (12.2%), rhinitis (12.2%), and diarrhea (9.8%) as the most common adverse events (AEs). Serious AEs documented included pneumonia (31.7%), bronchiolitis (4.9%), respiratory failure (4.9%), and hypotonia (4.9%).

The agent is currently being studied in a broad clinical trial program in SMA, with patients ranging from birth to 60 years old, and includes presymptomatic patients and those previously treated with other SMA-targeting therapies. In February, Genentech, PTC Therapeutics, and the SMA Foundation announced the drug had met its primary and key secondary end points in part 2 of the SUNFISH trial in patients with type 2 or 3 SMA.

In November 2019, risdiplam received a priority review designation, with a decision for approval initially expected by May 24, 2020. Although, after additional data were submitted by Roche in February 2020, the FDA announced in early April that it was pushing back its regulatory decision to August 24, 2020.

For more AAN coverage, click here.


Genentech’s risdiplam shows significant improvement in survival and motor milestones in infants with type 1 spinal muscular atrophy (SMA) [news release]. South San Francisco, CA: Genentech; Published April 28, 2020. Accessed April 28, 2020. businesswire.com/news/home/20200427005918/en/Genentech’s-Risdiplam-Shows-Significant-Improvement-Survival-Motor

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