SPINRAZA, the first FDA-approved treatment for adults with SMA1

Pivotal trial for
onset SMA2

The efficacy and safety of SPINRAZA was evaluated

CHERISH was a 15-month, phase 3, sham-controlled pivotal trial that evaluated changes in motor function as measured by HFMSE. Results showed patients ages 2-9 years old with later-onset SMA treated with SPINRAZA (n=84) experienced a 3.9-point increase in HFMSE score from a baseline of 22.4, compared to a 1.0-point decrease from a baseline of 19.9 in the sham-treated group (n=42).

Explore data from the largest observational real-world study of SPINRAZA in adults up to age 653

The Lancet



Study design: An independent, prospective, multicenter, observational cohort study

Study duration: Up to 14 months. Assessments made at 6, 10, and 14 months

Participants: 139 patients with genetically confirmed 5q later-onset SMA aged 16-65

Primary endpoint: Change from baseline in motor function measured by HFMSE at 6, 10, and 14 months. Patients with missing baseline HFMSE scores were excluded from these analyses

Secondary endpoints: Change from baseline in upper limb and walking ability measured by RULM and 6MWT at 6, 10, and 14 months

Study limitations: No control group; observational design. Study powered on primary endpoint only. Statistics for other endpoints are descriptive only

Safety: Adverse events (AEs) were generally consistent with those reported in the SPINRAZA clinical trials

  • Nausea
  • Diffuse pain
  • Constipation
  • Vertigo
  • Bladder disorder not otherwise specified
  • Infection
  • Meningitis, aseptic
  • Tinnitus, aggravated

Primary endpoint: Mean change from baseline in HFMSE score at 6, 10, and 14 months (95% CI)

HFMSE=Hammersmith Functional Motor Scale—Expanded.

SPINRAZA significantly increased mean HFMSE scores compared to baseline.3

139 patients completed an assessment at 6 months, 105 at 10 months, and 61 at 14 months. Patients not included at 10-month and 14-month assessments were those who had not reached the assessment time point (30 at month 10, 44 at month 14), were missing baseline or assessment values (15, 13, and 4 at month 6, 10, and 14), withdrew due an adverse reaction or procedure-related event (n=2), or withdrew due to consent (n=2). Greater improvement of motor function was correlated with lower severity of disease at baseline. Fourteen of 124 patients (11%) showed worsening motor function under treatment as measured by HFMSE.

≥3-point increase is considered clinically meaningful for HFMSE. A 1–2-point increase could be considered a positive outcome in a disease where natural history has shown a progressive decline.4,5

No new safety concerns were identified.

The majority of AEs were consistent with those in the SPINRAZA pivotal trials. Other reported AEs were:

  • Nausea
  • Diffuse pain
  • Constipation
  • Vertigo
  • Bladder disorder not
    otherwise specified
  • Infection
  • Meningitis, aseptic
  • Tinnitus, aggravated

Secondary endpoint: Mean change from baseline in RULM (95% CI)

RULM=Revised Upper Limb Module.

SPINRAZA improved mean upper limb function and walking distances compared to baseline at every study time point.3

After 6 months of treatment:

  • 28 (23%) of 120 patients showed ≥2-point improvement in RULM from baseline (ie, a clinically meaningful improvement)
  • 74 (61%) showed no meaningful change
  • 18 (15%) showed a decline of 1 point or more, and 10 (8%) showed a decline of ≥2 points
  • 75% (21/28) who saw clinically meaningful improvements in RULM at 6 months maintained these milestones at 14 months

Secondary endpoint: Mean change from baseline in 6MWT (95% CI)

6MWT=6-Minute Walk Test.

A 30-meter increase is considered clinically meaningful, and a 45-meter increase has been shown to greatly improve daily life challenges.6

In the largest observational study in adults with SMA taking SPINRAZA, mean motor function was improved3

*Number of patients in each group at 6, 10, and 14 months, respectively, was as follows: Type 2: 45, 30, and 20; Type 3: 77, 60, and 37; ambulant: 46, 35, and 23; nonambulant: 78, 57, and 34; baseline HFMSE ≥35: 39, 33, and 22; baseline HFMSE <35: 85, 59, and 35; previous spondylodesis: 28, 18, and 14; no previous spondylodesis: 96, 74, and 43.

SPINRAZA was evaluated for survival and overall motor function in pivotal trials.2,8