Biogen’s Spinraza (nusinersen) retards disease progression in pre-symptomatic spinal muscular atrophy (SMA) infants, allowing them to achieve motor milestones they would otherwise not reach, according to updated results of a Phase 2 clinical study.
The interim data were presented in a late-breaking session at the Annual Congress of the World Muscle Society Oct. 2-6 in Mendoza, Argentina.
SMA is caused by mutations in the SMN1 gene, leading to insufficiency or absence of the SMN protein, key for motor nerve cells and muscle function. While a second survival motor neuron gene (SMN2) is also capable of producing SMN, only 10 percent of the resulting protein is functional.
The number of SMN2 gene copies that a patient carries is inversely associated with disease severity. Two SMN2 copies are associated with a severe form of SMA (type 1), while three or more copies are linked to later disease onset and slower disease progression (types 2 or 3).
Spinraza works by increasing the ability of the SMN2 gene to produce a functional SMN protein, restoring its normal levels.
The ongoing Phase 2 NURTURE study (NCT02386553) is evaluating the safety and effectiveness of Spinraza in 25 infants genetically diagnosed with SMA and treated before symptom onset, compared with the disease’s natural course.
Fifteen infants were likely to develop type 1 SMA (two SMN2 copies) and the remaining 10 were most likely to develop type 2 or 3 SMA (three SMN2 copies).
As of May 2018, all 25 infants were alive (age 14 months and up) and did not require permanent ventilation, which contrasts significantly with the natural course of type 1 SMA.
These children also achieved several motor milestones — according to the motor milestone standard of the World Health Organization — with all of them being able to sit without support and 22 (88%) being able to walk either with or without assistance.
The infants’ motor skills were assessed through the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) score, ranging from 0 to 64, with higher scores indicating better motor function.
At the time of the analysis, the mean CHOP-INTEND scores of patients with three SMN2 copies was 62.6 and of those with two SMN2 copies was 61.0.
Spinraza was also well-tolerated in these patients, with no new safety concerns.
“The NURTURE study results demonstrate that early diagnosis and treatment with Spinraza has the potential to dramatically change the course of SMA,” Wildon Farwell, Biogen’s senior medical director of clinical development, said in a press release.
“This is the longest available span of data on infants with SMA who began treatment in a pre-symptomatic period and indicates that children treated early with Spinraza can achieve motor milestones they would likely not attain without treatment,” he added.
As a part of Biogen’s efforts to identify and validate new biomarkers of SMA, the company presented additional data on phosphorylated neurofilament heavy chain (pNF-H), a major component of motor nerve cells.
Increased levels of pNF-H have been previously associated with nerve cell damage in the central nervous system (spinal cord and brain), supporting pNF-H as a potential biomarker of motor nerve cell damage.
The company compared the blood levels of pNF-H of more than 300 SMA patients who participated in Spinraza clinical trials (including those in the NURTURE study) with those of healthy individuals.
Patients treated with Spinraza showed a fast reduction in pNF-H levels, followed by stabilization at levels close to those of healthy people, suggesting that pNF-H could be used to monitor treatment response or disease progression.
“We … are encouraged by the potential of neurofilament [pNF-H] as a biomarker for SMA, how it could further expand the scientific understanding of this rare disease and, more importantly, its potential impact on those living with SMA,” Farwell said.