Roche's risdiplam shows significantly improved, stabilised motor function in patients with SMA type 2, 3

Roche on Thursday detailed results from Part 2 of the pivotal SUNFISH study, demonstrating that patients, including adults, with type 2 or 3 spinal muscular atrophy (SMA) achieved a significant 1.55-point mean improvement from baseline on the primary endpoint of the Motor Function Measure (MFM-32) scale at 12 months, compared with placebo. The drugmaker, which is leading development of the experimental SMN2 splicing modifier, also known as RG7916, in partnership with PTC Therapeutics and the SMA Foundation, said the data were presented at the International Scientific and Clinical Congress on SMA. 

"We are very encouraged by the positive results in this broad group of SMA patients, many of whom are under-served and under-represented in clinical trials," commented Levi Garraway, Roche's head of global product development. 

Part 1 of the SUNFISH study determined the dose for the second confirmatory portion of the trial, which involved 180 patients aged two to 25 years with non-ambulatory type 2 and type 3 SMA. The primary endpoint evaluated motor function at 12 months using total score of MFM-32 scale, which assesses fine and gross motor function in patients with neurological disorders, including SMA. 

PTC noted that "as expected," the strongest responses were observed in the youngest age group of patients, those between two and five years old, with 78.1% achieving a point increase of 3 or more on the MFM-32 scale, compared with 52.9% for placebo. The company added that stabilisation, defined as either no change or an improvement on the MFM-32 scale, is the treatment goal among older patients, aged 18 to 25 years, who have more established disease, with 57.1% achieving stabilisation versus 37.5% for placebo. 

The trial also hit a key secondary endpoint, with risdiplam-treated patients achieving a significant 1.59-point improvement on the Revised Upper Limb Module (RULM) from baseline, versus placebo. Roche said the scale, which measures upper limb movement in people with SMA, "can capture progressive muscle weakness across the spectrum of the disease, reflective of the SUNFISH Part 2 study population." Meanwhile, the secondary endpoint of total change from baseline on the Hammersmith Functional Motor Scale Expanded (HFMSE) was not met versus placebo, although there was a numerical difference in favour of risdiplam. PTC said patients and caregivers also reported numerical improvements in independence as measured by the SMA Independence Scale, a new measurement that captures "highly relevant, day-to-day activities such as eating and drinking, getting dressed, and overall hygiene," among others. 

The FDA granted priority review for risdiplam last November, with a decision on approval expected by May 24. Along with data from the SUNFISH trial, the submission also includes 12-month results from the pivotal FIREFISH study investigating risdiplam in infants aged one to seven months with Type 1 SMA. 

For related analysis, see ViewPoints: Experts' enthusiasm for Roche's risdiplam grows as FDA grants priority review.

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