Rates of survival are higher, and respiratory intervention rates are lower, in 25 infants with presymptomatic 5q spinal muscular atrophy (SMA) treated with Spinraza (nusinersen). Biogen announced these new interim results from their NURTURE trial; this is an ongoing open-label, single-arm efficacy and safety phase 2 study of Spinraza in 25 presymptomatic infants with SMA. The data were presented in a late-breaking session at the 23rd Annual Congress of the World Muscle Society (WMS; 2–6 October, Mendoza, Argentina).
The interim analysis evaluated survival and respiratory intervention rates in 25 infants who were genetically diagnosed with presymptomatic SMA and also began treatment in the presymptomatic stage of the disease. As of May 2018, all patients in the study were alive and none required tracheostomy or permanent ventilation. Additionally, 22 of the 25 participants were able to walk with assistance, 17 participants were able to walk independently according to the motor milestone standard of the World Health Organization, and all 25 were able to sit without support.
“The NURTURE study results demonstrate that early diagnosis and treatment with nusinersen has the potential to change the course of SMA,” says Wildon Farwell, senior medical director, clinical development at Biogen. “This is the longest available span of data on infants with SMA who began treatment in a presymptomatic period and indicates that children treated early with nusinersen can achieve motor milestones they would likely not attain without treatment.”
The motor skills of study participants were also evaluated using the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND), an assessment which considers 16 different types of movement to create an overall score between zero and 64. The mean CHOP INTEND scores were 62.6 (min, max: 58, 64) for study participants with three copies of the SMN2 gene and 61 (46, 64) for those with two copies of the gene.
All NURTURE study participants were 14 months or older at the time of the analysis (median: 26 months; range: 14–34.3 months). Participants included infants with two copies of the SMN2 gene (15 of the 25 patients) who are likely to develop an often fatal, early-onset form of SMA known as Type 1, and infants with three copies of the SMN2 gene (the remaining 10 of the 25 infants) who typically develop SMA Type 2 or 3. People living with SMA Types 2 and 3 may never be able to walk or will lose that ability over time. No specific safety concerns were identified.
Additional research presented at WMS looked into possible biomarkers for SMA. The investigators compared levels of phosphorylated neurofilament heavy chain (pNF-H) in plasma in more than 300 patients from nusinersen clinical trials, including those in the NURTURE study, and a control group of people without SMA. The data demonstrated that treatment with nusinersen is associated with a rapid decline from baseline followed by stabilisation of pNF-H in plasma at levels close to those of healthy controls.
For those patients with two SMN2 copies, the mean pNF-H concentration was 1,447pg/mL at 788 days. Individuals with three SMN2 copies had a pNF-H concentration of 315.4 at 540 days. In contrast, the median plasma pNF-H in children without SMA aged less than one year is 1,510 pg/mL. The results are part of Biogen’s ongoing work to identify and validate biomarkers that could provide insight on the disease progression of SMA.
“We continue to develop tools to inform our clinical research and are encouraged by the potential of neurofilament 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,” concludes Farwell.
Recently, the UK’s National Institute for Health and Care Excellence (NICE) published its Appraisal Consultation Document (ACD) outlining a ‘minded no’ for the routine funding of Spinraza (nusinersen) for the treatment of SMA in England, Wales and Northern Ireland, triggering vice president and managing director of Biogen UK and Ireland Terry O’Regan to urge NICE and NHS England to continue to work with the company on agreeing the terms of a managed access agreement (MAA), “so that patients in England, Wales and Northern Ireland can share equality in access compared to other countries across Europe and the world.”