New data presented at AAN meeting highlights clinically meaningful benefits of Spinraza to treat spinal muscular atrophy,. Biogen Inc.

Biogen Inc. announced new data affirming the safety and durability of Spinraza (nusinersen) and highlighting its clinically meaningful benefits for individuals with spinal muscular atrophy (SMA). Data from the SHINE extension study, with patients followed for up to four years, the NURTURE study of pre-symptomatic infants and an evaluation of phosphorylated neurofilament heavy chain (pNF-H) as a biomarker will be featured presentations at the 71st annual meeting of the American Academy of Neurology (AAN) in Philadelphia, PA (May 4-10, 2019).

Interim results from the ENDEAR-SHINE open-label extension study of infants (n=89) followed for up to four years demonstrated that treatment with Spinraza resulted in additional or new motor function improvements on the Children�s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND). The infants also exhibited improved event-free survival rates compared to the natural history of the disease. There were no new safety findings. Additional highlights from ENDEAR-SHINE include: As of October 15, 2018, study participants who received Spinraza in ENDEAR and SHINE (n=65) increased average CHOP INTEND score by 16.8 points after nearly three years of treatment. Those in the sham-control arm in ENDEAR and that received Spinraza in SHINE (n=24) increased average CHOP INTEND score by 8.2 points after over 1.5 years of treatment. Patients receiving Spinraza in ENDEAR and SHINE continued to achieve motor milestones during SHINE. Both those who began treatment younger (n=30, less than or equal to 5.42 months) and older (n=21, greater than 5.42 months) demonstrated the ability to sit without support, 60 and 38 percent respectively. At nearly three years of follow-up, infants in the younger age group demonstrated greater improvements in CHOP INTEND score (19.4 vs. 13.8 points). Patients treated with Spiraza in ENDEAR and SHINE demonstrated a longer period of survival without need for permanent ventilation (median 75.0 weeks). This compared to event-free survival among patients initiating treatment in SHINE (median 22.6 weeks). Among patients who received sham in ENDEAR and Spinraza in SHINE, the median time of event-free survival was reached in ENDEAR while untreated. Among infants who initiated treatment in SHINE and were alive without permanent ventilation at baseline, 58 percent remained alive without permanent ventilation at the data cutoff.

Data from CHERISH-SHINE, which evaluated individuals with later-onset SMA (n=125, most likely to develop SMA Type 2 or 3), demonstrated that earlier treatment resulted in greater improvements in motor function and continued improvement or stabilization of motor function scores. Mean change in Hammersmith Functional Motor Scale Expanded (HFSME) score was 3.7 for participants treated with Spinraza in SHINE and CHERISH. This compared to a positive 0.4 change from baseline among participants in the CHERISH sham-control arm and who received Spinraza in SHINE. During CHERISH, sham-control participants experienced a 0.4 decline in HFSME. Four participants in the youngest age group in the study (n=39, less than 3.69 years) were walking independently at Day 690 compared to no patients at baseline. There were no new safety findings. Patients were followed for up to four years, adding to the long-term safety profile of Spinraza.

Data from the NURTURE study showed that pre-symptomatic treatment of infantile-onset SMA (n=25, most likely to develop SMA Type 1 or 2) resulted in motor milestone achievements more consistent with normal motor development. Evaluations were conducted at a median age of 26 months. All infants were able to sit without support and 88 percent could walk with assistance and 77 percent could walk without assistance. All infants were alive and none required permanent ventilation. No new safety concerns were identified. In the natural history of SMA, individuals are unable to sit without support (SMA Type 1) or walk (SMA Type 1 or 2) and often require respiratory and nutritional interventions in order to live past the age of two (SMA Type 1). The May 2018 data was previously presented.

An evaluation of pNF-H in plasma highlighted its potential to predict disease activity and suggested that it may be a useful biomarker in SMA. Baseline measure of pNF-H was higher in individuals with SMA (n=302) than those without SMA (n=34). Individuals from the NURTURE, ENDEAR and CHERISH studies treated with Spinraza experienced rapid pNF-H declines followed by stabilization at lower levels. The results are part of ongoing work to identify biomarkers that could provide insight on disease progression in SMA.