PTC Therapeutics announced interim data from Part 1 of its open-label clinical trials, FIREFISH and SUNFISH, of risdiplam for Type 1, 2 and 3 spinal muscular atrophy in collaboration with Genentech.
PTC Therapeutics, based in South Plainfield, NJ, announced interim data from Part 1 of its open-label clinical trials, FIREFISH and SUNFISH, of risdiplam (RG7916) for Type 1, 2 and 3 spinal muscular atrophy (SMA). PTC Therapeutics is collaborating with Genentech, a subsidiary of Roche, in the trials.
SMA is a genetic neuromuscular disease caused by a mutated or defective survival of motor neuron 1 (SMN1) gene. The disease results in the loss of nerve cells called motor neurons, in the spinal cord and the part of the brain that controls the spinal cord. This leads to weakness and atrophy of the muscle, and in the most severe cases, the muscles for breathing and swallowing. According to the Orphanet Journal of Rare Diseases, the estimated incidence is 1 in 6,000 to 1 in 10,000 live births.
Type 1 SMA is also called Werdnig-Hoffman disease, and it is seen at birth or within a few weeks of birth. It is the most severe form. Type 2 is seen in children between the ages of 6 and 12 months and is characterized by muscle weakness. Although unable to stand or walk unaided, they typically can sit without support. Type 3 is also called Kugelberg-Welander disease or juvenile type. It has mild symptoms that generally show up between early childhood and adolescence. Patients with type 3 can stand and walk without help, but walking and climbing stairs can become increasingly difficult.
PTC’s interim data show increases in developmental motor milestones in all three types. It was well-tolerated and no patients dropped out of the trials because of safety issues. In Part 1 of the FIREFISH trial, 43 percent of infants at Day 245 were able to sit with or without support. At this time, 90 percent of the babies are still alive, although two have discontinued because of their disease.
In Part 1 of the SUNFISH trial in Type 2 and 3 patients, 63 percent receiving the drug for at least one year had a median increase in motor function of 3.13 points compared to baseline. Patients in this category typically decline in motor function by 0.85 to 0.67 points each year. In addition, the SMN protein level that increased more than 2-fold were sustained over the year.
The company expects to present data at the 23rd International Annual Congress of the World Muscle Society in Argentina.
Risdiplam is a small molecule SMN2 splicing modifier that targets SMN2 RNA, which results in a functional transcript. The drug is oral, crosses the blood-brain barrier, and shows systemic distribution.
“The emerging results from FIREFISH and SUNFISH trials support the broad clinical benefit of a systemic oral treatment for SMA patients,” stated Stuart W. Peltz, PTC’s chief executive officer. “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.”
Although there are currently at least 16 active programs in the industry for SMA, the only approved therapy is Biogen’s Spinraza (nusinersen), which got the nod in December 2016 from the U.S. Food and Drug Administration (FDA). The drug is not without its controversy, although mostly around price. Biogen gave it a price tag of $750,000 for the first year and $375,000 for each year afterward. Patients receive six injections in the first year at about $125,000 per shot.
