Rare Daily Staff
Roche said interim clinical data from the dose-finding parts of two pivotal studies of its experimental spinal muscular atrophy drug risdiplam showed infants treated with the drug surviving and achieving developmental milestones.
Spinal Muscular Atrophy (SMA) is a severe, inherited, progressive neuromuscular disease that causes devastating muscle atrophy and disease-related complications. It is the most common genetic cause of infant mortality and one of the most common rare diseases, affecting approximately one in 11,000 babies. SMA leads to the progressive loss of nerve cells in the spinal cord that control muscle movement. Depending on the type of SMA, an individual’s physical strength and their ability to walk, eat or breathe can be significantly diminished or lost.
SMA is caused by a mutation in the survival motor neuron 1 (SMN1) gene that results in a deficiency of SMN protein. SMN protein is found throughout the body and increasing evidence suggests SMA is a multi-system disorder and the loss of SMN protein may affect many tissues and cells throughout the body.
Risdiplam is an investigational, oral medicine that is systemically distributed and designed to increase SMN protein levels in the CNS and throughout the body. It is designed to help the SMN2 gene produce more functional SMN protein, to better support motor neurons and muscle function. Roche is leading the clinical development of risdiplam in collaboration with the SMA Foundation and PTC Therapeutics.
In the FIREFISH study, an open-label trial in infants aged 1-7 months with Type 1 SMA, six out of 14 infants (43 percent) were able to sit (with or without support), including three (21 percent) who achieved unassisted stable sitting after eight months of treatment. In addition, four infants (29 percent) demonstrated rolling to the side; seven (50 percent) kicking and six (43 percent) achieved upright head control.
The data were presented at the 23rd International Annual Congress of the World Muscle Society in Mendoza, Argentina.
“We are highly encouraged by these data showing infants treated with risdiplam surviving and achieving developmental milestones beyond the natural history of this devastating disease,” said Sandra Horning, Roche’s chief medical officer and head of global product development. “SMA therapies that produce a sustained increase in SMN protein in both the CNS and periphery may provide comprehensive benefits to people diagnosed with SMA, and we look forward to sharing additional data on risdiplam as the clinical program progresses.”
Updated analyses of a scale developed to assess motor function in infants with Type 1 SMA, demonstrated that eight out of 14 infants in FIREFISH (57 percent) achieved a score of 40 or above at their eight-month visit. Typically, an infant with Type 1 SMA does not demonstrate any motor improvement and can decline during this time period.
The most common adverse events were fever (52.4 percent), diarrhea (26.8 percent), upper respiratory tract infections (19 percent), ear infections (14.3 percent), pneumonia (14.3 percent), constipation (14.3 percent), vomiting (14.3 percent), cough (14.3 percent) and upper respiratory tract inflammation (14.3 percent).
In Part 1 of the SUNFISH study, a double-blind, placebo-controlled trial in children and young adults (2-25 years old) with Type 2 and 3 SMA, SMN protein median increases of greater than two-fold were seen after 12 months.
Of the patients treated with risdiplam for at least one year, the median change from baseline in a scale used to assess motor function in neuromuscular disease, the primary endpoint in the confirmatory part of SUNFISH, showed a 3.1-point improvement. Some 63 percent of patients experienced an improvement in scores over baseline of three points or more after one year. Such improvements were seen both in patients under 12 years old (76 percent) and above 12 years old (46 percent).
Serious adverse events that occurred in two or more of the 51 patients exposed to risdiplam were nausea (4 percent), upper respiratory tract infection (4 percent), and vomiting (4 percent).
Follow up is ongoing for the confirmatory part 2 portions of both studies.
October 4, 2018
Sandra Horning, Roche’s chief medical officer and head of global product development