CAMBRIDGE, Mass.—In early May, Biogen Inc. announced new data affirming the safety and durability of Spinraza (nusinersen), highlighting its clinically meaningful benefits for individuals with spinal muscular atrophy (SMA).
Data from the SHINE extension study (in which patients were followed for up to four years), the NURTURE study of pre-symptomatic infants, and an evaluation of phosphorylated neurofilament heavy chain (pNF-H) as an SMA biomarker were featured at the 71st annual meeting of the American Academy of Neurology (AAN) in Philadelphia.
“Each milestone in these studies marks a new chapter in what it means to live with SMA, and the insight provided is invaluable in understanding the long-term experience of this rare disease,” explained Dr. Alfred Sandrock, Jr., executive vice president and chief medical officer of Biogen. “These results confirm previous data from our trials, which demonstrated that early treatment with Spinraza can make a critical difference in survival and achieving motor milestones. The data also demonstrate that improvements in motor milestones were achieved in individuals who began treatment with Spinraza at a later age. This is a powerful development for the SMA community.”
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). Infants had improved event-free survival rates compared to the natural disease history. There were no new safety findings.
As of Oct. 15, 2018, study participants who received Spinraza in ENDEAR and SHINE (n=65) increased average CHOP INTEND score by 16.8 points after about three years of treatment. Those in the sham-control arm in ENDEAR and who 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. 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 Spinraza in ENDEAR and SHINE demonstrated a longer period of survival without need for permanent ventilation (median 75.0 weeks). This was comparative to event-free survival among patients initiating treatment in SHINE (median 22.6 weeks, 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), 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 (HFMSE) score was 3.7 for participants treated with Spinraza in SHINE and CHERISH, compared to a +0.4 change from baseline among participants in the CHERISH sham-control arm.
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 zero patients at baseline. Patients were followed for up to four years, adding to the long-term safety profile of Spinraza.
SVB Leerink LLC spoke with MEDACorp KOL [key opinion leader] neurologists on May 7 to cover the recent SMA data and presentations in SMA at AAN this year. Analysts and KOLs appear to be wary—not of Spinraza itself, but of its delivery method.
“Both KOLs were careful in directly comparing efficacy of Spinraza, AVXS-101 and risdiplam based on the differences in patient baseline characteristics, with particular emphasis on wide variation in age at treatment initiation between the studies,” said Leerink analysts. “Those caveats in place, given the profile seen to date, they believe that Zolgensma [AVXS-101] will capture most eligible Type 1 and presymptomatic patients as families gravitate to a one-time therapy due to the fact that treatment can never be taken away, families will not be dependent on insurance and access to care to maintain treatment in the future, lower treatment burden compared to repeated intrathecal injections, and no need for compliance with a lifelong oral regimen.”
“From the doctors’ perspective, treatment with Spinraza creates a substantial operational burden—both KOLs noted doctors, nurses, administrative coordinators, and physical therapy staff are specifically dedicated to Spinraza administration at their respective treatment centers,” Leerink analysts continued. “Based on this, the treatment burden on neurologists from Spinraza is likely to color physician views of Zolgensma and risdiplam, as treating patients with these agents in place of Spinraza would provide relief from the intrathecal injection burden…”
Leerink analysts pointed out that “there are competitors coming after the top and bottom ends of patient severity in the Spinraza franchise. While we are not yet convinced that the efficacy for Roche’s risdiplam is exactly as good as Spinraza, Roche is likely to find many eager patients and providers willing to migrate away from the burden of spinal taps every 3–4 months to a once/day oral medicine.”
Data from the NURTURE study showed that pre-symptomatic treatment of infantile-onset SMA (n=25) resulted in motor milestone achievements more consistent with normal motor development. Evaluations were conducted at a median age of 26 months. All infants could sit without support, 88 percent could walk with assistance and 77 percent could walk without assistance. All infants were alive, and none required permanent ventilation.
“The newest NURTURE update of Spinraza in presymptomatic SMA patients presented at AAN provides additional evidence that outcomes for all SMA patients are better the earlier treatment is initiated,” noted Leerink analysts. “While this view is widely held among neurologists, the data update should support efforts to expand newborn screening efforts and support use of disease-modifying treatments in patients identified through newborn screening.”
An evaluation of pNF-H in plasma highlighted its potential to predict disease activity, and suggested that pNF-H may be a useful biomarker in SMA. Baseline measure of pNF-H was higher in individuals with SMA (n=302) than those without (n=34). Individuals from NURTURE, ENDEAR and CHERISH 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.