-- All children (100%) treated presymptomatically in the SPR1NT two-copy 
      cohort survived without respiratory or nutritional support, and sat 
      independently for >=30 seconds, most (11/14) within the WHO window of 
      expected normal development 
 
   -- The majority of children (82%) treated in STR1VE-EU achieved 
      developmental motor milestones not observed in the natural history of SMA 
      Type 1, including patients with more severe disease 
 
   -- More than 1,200 patients have now been treated with Zolgensma globally 
      across clinical trials, managed access programs, and in the commercial 
      setting1

Basel, June 18, 2021 -- Novartis today announced data that reinforce the transformational benefit of Zolgensma(R) (onasemnogene abeparvovec), an essential, one-time treatment and the only gene therapy for spinal muscular atrophy (SMA). New late-breaker data from the completed two-copy cohort of the Phase 3 SPR1NT clinical trial demonstrate age-appropriate milestone development in presymptomatic children with SMA without respiratory or nutritional support of any kind, and with no serious, treatment-related adverse events. The completed Phase 3 STR1VE-EU trial demonstrated rapid improvements in motor function following treatment with Zolgensma, and the majority of patients achieved motor milestones not observed in the natural history of SMA Type 1. Safety remained consistent with previously reported data. The data will be presented at the European Academy for Neurology (EAN) Virtual Congress 2021.

The Zolgensma data represent a significant contrast to the natural history of SMA Type 1, which leads to progressive and irreversible loss of motor function and if left untreated, often death or permanent ventilation by the age of two years.(2,3) Remarkably, all children (100 percent) treated presymptomatically in the SPR1NT two-copy cohort achieved event-free survival, were independent of respiratory and nutritional support and met the primary endpoint of sitting independently for >=30 seconds, including 11/14 (79 percent) who achieved this milestone within the World Health Organization (WHO) window of normal development.(4) A majority of patients went on to stand independently (11/14) and walk independently (9/14), most within the typical range of normal development.(4)

Among symptomatic children with SMA Type 1 treated in the STR1VE-EU trial, including patients with more severe disease at baseline, the majority of children (82 percent) achieved developmental motor milestones not observed in the natural history of SMA Type 1, including 16 children (49 percent) who sat without support for >=30 seconds.(5)

"With more than 1,200 children now treated, these data presented at EAN further reinforce the life-changing benefit of a one-time treatment of Zolgensma," said Shephard Mpofu, M.D., SVP, Chief Medical Officer, Novartis Gene Therapies. "When treated with Zolgensma prior to the onset of symptoms, not only did all patients survive, but were thriving -- breathing and eating on their own and sitting independently, with many standing and walking. When you consider these newborns would go on to develop severe symptoms of SMA Type 1, a devastating, progressive disease that robs children of the ability to talk, eat, sit up and even breathe, findings from the SPR1NT trial are nothing short of extraordinary."

"STR1VE-EU included some patients with more severe SMA at baseline, yet the study demonstrated consistent and significant therapeutic benefit for symptomatic children with SMA Type 1," said Professor Eugenio Mercuri, M.D., PhD., Department of Pediatric Neurology, Catholic University, Rome, Italy. "This is a remarkable outcome that adds to the robust body of clinical evidence for Zolgensma showing that even among patients with more severe disease, Zolgensma was highly effective and demonstrated a consistent safety profile."

Final Phase 3 SPR1NT Two-Copy Cohort Results

SPR1NT is a Phase 3, open-label, single-arm, multi-center trial designed to evaluate the safety and efficacy of a one-time intravenous (IV) infusion of Zolgensma in presymptomatic patients with a genetic diagnosis of SMA and two or three copies of SMN2 who were <=6 weeks of age. Fourteen patients with two copies of SMN2 and 15 patients with three copies of SMN2 were treated. The majority of patients with two copies of SMN2 develop SMA Type 1, the most common form accounting for 60 percent of cases. Data reported at EAN reflect the final data cut for SPR1NT two-copy patients. Mean age at dosing in the two-copy cohort was 20.6 days (8 -- 34 days). The study of the three-copy cohort is ongoing.

Two-copy cohort (n=14) final results: 


   -- One hundred percent of patients (14/14) met the secondary endpoint of 
      survival without ventilatory support of any kind at 14 months of age,4 
      versus only 26 percent of patients in the Pediatric Neuromuscular 
      Clinical Research (PNCR) natural history cohort.6 
 
   -- All patients (100 percent) achieved the primary endpoint of sitting 
      independently for at least 30 seconds, including 11 (79 percent) who 
      achieved this milestone within the WHO window of normal development.4 
 
   -- Eleven patients (79 percent) could stand independently, seven of whom 
      achieved this milestone within the WHO window of normal development.4 
 
   -- Nine patients (64 percent) could walk independently, five of whom 
      achieved this milestone within the WHO window of normal development.4 
 
   -- All patients (100 percent) were independent of nutritional and 
      respiratory support for the duration of the study.4 
 
          -- Nearly all patients (13/14) achieved the additional secondary 
             efficacy endpoint of age-appropriate weight maintenance without 
             non-oral feeding support at any visit up to 18 months of age.4 
 
   -- All patients (100 percent) achieved or maintained a Children's Hospital 
      of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) 
      score of >=58.4 According to natural history, untreated patients with SMA 
      Type 1 almost never achieve a CHOP INTEND score of >=40.6 
 
   -- All patients (100 percent) had Bayley-III fine motor performance scores 
      similar to same-age peers without SMA and the majority (64 percent) had 
      gross motor performance scores similar to same-age peers without SMA.4

All patients experienced at least one adverse event (AE) after dosing, 10 (71 percent) of which were considered to be treatment-related.(4) There were no serious, treatment-related AEs. Five patients were reported to have had serious adverse events (SAEs), all of which resolved and were not related to treatment.(4)

Final Phase 3 STR1VE-EU Results

STR1VE-EU was designed to evaluate the efficacy and safety of a single, one-time IV infusion of Zolgensma in patients with SMA Type 1 who had bi-allelic SMN1 gene deletion or point mutations and one or two copies of the SMN2 backup gene, and were less than six months of age. Mean age at dosing was 4.1 months, and mean age at symptom onset was 1.6 months. The mean CHOP INTEND score at baseline was 28. All patients had two SMN2 copies and were symptomatic with a variable degree of severity. Patients with SMA Type 1 not treated with disease-modifying therapy will never sit unassisted. If left untreated, SMA Type 1 leads to death or permanent ventilation by the age of two in the majority of cases.(2,) (3)

STR1VE-EU was distinct in its broadened inclusion and exclusion criteria of enrolled patients compared with START or STR1VE-US. Some patients in STR1VE-EU had a more severe disease at baseline, including lower CHOP INTEND scores and the need for nutritional and ventilatory support.(5) Of the 33 patients enrolled, nine (27%) required feeding support, an additional nine (27%) required ventilatory support and five (15%) required both at baseline.(5)

STR1VE-EU (n=33) final results: 


   -- Thirty-three patients were enrolled; and 32 patients completed the study. 
 
   -- Twenty-seven of 33 patients (82 percent) achieved developmental motor 
      milestones not observed in the natural history of SMA Type 1.5 
 
   -- Fourteen of 32 patients (44 percent) in the intention-to-treat (ITT) 
      population achieved the primary endpoint of sitting independently for 
      >=10 seconds, observed at a median age of 15.9 months (7.7--18.6). The 
      patient who was not in the ITT population also achieved this primary 
      outcome measure.5 
 
   -- Twenty-three of 30 patients (77 percent) achieved head control (three 
      already had control at baseline), 19 of 33 (58 percent) rolled from back 
      to sides and 16 patients (49 percent) sat without support for >=30 
      seconds, including all patients who met the primary endpoint of sitting 
      without support for >=10 seconds.5 
 
   -- In addition, two patients stood with assistance, and one crawled, stood, 
      pulled to stand, and walked without assistance, all by 18 months of age.5 
 
   -- Thirty-one of 32 patients (97 percent) achieved the secondary efficacy 
      endpoint of survival, free from permanent ventilatory support at 14 
      months,5 compared with a quarter of patients (26 percent) in the PNCR 
      natural history cohort.6 
 
   -- The majority of patients (73 percent) achieved a CHOP INTEND score of 
      >=40 points, 14 (42 percent) achieved a score of >=50 points and three (9 
      percent) achieved a score of >=58 points.5 According to natural history, 
      untreated patients with SMA Type 1 almost never achieve a CHOP INTEND 
      score >=40.6 
 
   -- Thirteen of 33 patients (39 percent) remained independent of any type of 
      daily ventilatory support at 18 months of age,5 compared with none in the 
      PNCR data set.6 
 
   -- Of the nine patients who required ventilatory support at baseline, two 
      achieved independence, and of the 24 patients who did not require 
      ventilatory support at baseline, a majority of patients (67 percent) 
      remained free from this support at the end of the study.5

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June 18, 2021 12:30 ET (16:30 GMT)