PTC Therapeutics announced interim clinical data from the Part 1, open-label studies of FIREFISH and SUNFISH demonstrating the benefit of risdiplam (RG7916) for the treatment of Type 1, 2 and 3 spinal muscular atrophy (SMA). The results showed that patients across all SMA types benefited from an oral systemic therapy indicated by increases in developmental motor milestones. Risdiplam was well tolerated at all doses across studies to date and no participants have withdrawn due to drug-related safety findings. The pivotal portions of both studies are ongoing. The data were presented at the 23rd International Annual Congress of the World Muscle Society in Argentina. The SMA program is a collaboration between PTC, the SMA Foundation, and Roche.
"The emerging results from FIREFISH and SUNFISH trials support the broad clinical benefit of a systemic oral treatment for SMA patients," said Stuart W. Peltz, Ph.D., Chief Executive Officer of PTC Therapeutics. "Patients with Type 2 and 3 SMA typically decline over the course of a year and the increase in motor function by over 3 points in SUNFISH when compared to natural history is exceptionally encouraging. We are excited by the gains in developmental motor milestones exhibited by Type 1 babies in FIREFISH. The observation of six babies sitting to date in a dose finding study is remarkable. SMA is a systemic disease, and risdiplam which is an oral treatment that reaches all affected organs has the potential to be a best-in-class therapy."
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In Part 1 of the FIREFISH study, at Day 245 of treatment, 43% (6/14) of infants were able to sit (with or without support), including three who achieved unassisted sitting. Natural history indicates that Type 1 SMA babies never achieve this milestone. Ninety percent of babies remain alive with two having discontinued due to the fatal progression of their disease. In Part 1 of the SUNFISH study in Type 2 and 3 SMA patients, 63% (19/30) of patients treated with risdiplam for at least one year achieved a median increase in motor function (as measured by MFM32) of 3.13 points versus baseline. Typically patients with Type 2 or 3 SMA decline by 0.85 to 0.67 point per year. In addition, median SMN protein level increases of greater than 2-fold were sustained over 12 months.
The pivotal portion of the SUNFISH clinical study has completed enrollment. Part 2 of SUNFISH is a randomized, double-blinded, multi-center, placebo-controlled study which enrolled 180 Type 2 and Type 3 SMA patients 2-25 years of age for 24 months, followed by an open-label extension. Patients enrolled in the SUNFISH trial have a broad age range (2-24 years; median age 8 years) and with broad functional characteristics. The primary endpoint is change from baseline in the total Motor Function Measure 32 (MFM-32) score at Month 12.
Risdiplam is an investigational small molecule SMN2 splicing modifier targeting the survival motor neuron 2 (SMN2) RNA, restoring a functional transcript. In preclinical studies, risdiplam, which was given orally, crossed the blood brain barrier, and showed systemic distribution to the organs that are affected by low levels of SMN protein.
The most common adverse events were fever (pyrexia: 52.4%,) diarrhea (26.8%), upper respiratory tract infections (19%), ear infections (14.3%), pneumonia (14.3%), constipation (14.3%), vomiting (14.3%), cough (14.3%) and upper respiratory inflammation (14.3%). Data cutoff: 7-Sept 2018.