WHY SPINRAZA/LATER-ONSET EFFICACY

SPINRAZA has proven efficacy in presymptomatic, early-, and later-onset SMA1

Pivotal trial: CHERISH1,2

Study: A phase 3, multicenter, randomized (2:1), double-blind, sham procedure–controlled trial

Treatment duration: 15 months

Participants: 126 patients with later-onset SMA, aged 2 to 9 years at screening

Primary endpoint: Least-squares mean change from baseline in the HFMSE at 15 months of treatment

Select secondary endpoints: Clinically meaningful change in HFMSE ≥3 points and change in upper limb function as measured by RULM

Study limitations: Differences in dosing compared with the approved SPINRAZA schedule

Safety: The most common side effects were fever (43%), headache (29%), vomiting (29%), and back pain (25%)

HFMSE=Hammersmith Functional Motor Scale—Expanded; RULM=Revised Upper Limb Module.

Significant improvements seen in overall motor function1,2

Motor function began to steadily improve in just 6 months compared with untreated group

HFMSE=Hammersmith Functional Motor Scale—Expanded.

Learn more about the mobility measures used in the SPINRAZA clinical trials

Learn more about the mobility measures used in the SPINRAZA clinical trials

Review the warnings and precautions, including thrombocytopenia, coagulation abnormalities, and renal toxicity1

In additional data from multiple independent real-world studies,
SPINRAZA showed clinical benefit in adults with later-onset SMA3

Independent, observational study from The Lancet Neurology4

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 to 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 6-Minute Walk Test (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: The majority of adverse events (AEs) were generally consistent with those reported in the SPINRAZA clinical trials. Other reported AEs were:

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

HFMSE=Hammersmith Functional Motor Scale—Expanded; RULM=Revised Upper Limb Module.

Not a Biogen-sponsored study. Biogen-sponsored pivotal trials for SPINRAZA did not include adults with SMA.

One of the largest real-world studies of SPINRAZA included 139 adults with later-onset SMA up to age 653,4

HFMSE=Hammersmith Functional Motor Scale—Expanded.

SPINRAZA significantly increased mean HFMSE scores compared with baseline

14 of 124 patients (11%) showed worsening motor function under treatment as measured by HFMSE. 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, respectively), had an adverse reaction or procedure-related event (n=2), or withdrew consent (n=2). Greater improvement of motor function was correlated with lower severity of disease at baseline.

Exploratory endpoint.

≥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

SPINRAZA improved mean upper limb function and walking distance compared with baseline at every study time point4

*For individuals with later-onset SMA, clinically meaningful was defined as an improvement in RULM score of at least 2 points.

Lower bound of 95% CI not shown.

RULM=Revised upper limb module.

  • 75% (21/28) who saw clinically meaningful improvements* in RULM at 6 months maintained these milestones at 14 months
  • At 6 months, 28 (23%) of 120 patients showed ≥2-point improvement in RULM from baseline (ie, a clinically meaningful improvement), whereas 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

*For individuals with later-onset SMA, clinically meaningful was defined as an improvement in RULM score of at least 2 points.

§Lower bound 95% CI not shown.

6MWT=6-Minute Walk Test.

Start your patient on SPINRAZA

Independent, retrospective, observational study from The Journal of Neurology, Neurosurgery and Psychiatry1,3

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

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

Participants: 116 patients with later-onset SMA Type 2 (n=13) and Type 3 (n=103), aged 18-72

Primary outcomes: Change from baseline in motor function measured by HFMSE, RULM, and 6MWT at 6, 10, and 14 months

  • Clinically meaningful response was defined as a ≥3-point increase in HFMSE, ≥2-point increase in RULM, or ≥30-meter increase in 6MWT

Study limitations: No control group; retrospective observational design; missing data for some clinical assessment variables; and a small number of patients with SMA Type 2 (n=13)

Safety: The majority of AEs were generally consistent with those in the SPINRAZA clinical trials

  • The most frequently reported AEs were postprocedural headache (37.1%) and lumbar pain (8.6%)
  • 5 patients were hospitalized for headache
  • Other reported AEs were transient worsening of existing hand tremor (2 patients) and renal colic (1 patient)

AEs=adverse events; HFMSE=Hammersmith Functional Motor Scale—Expanded; RULM=Revised Upper Limb Module; 6MWT=6-Minute Walk Test.

Not a Biogen-sponsored study. Biogen-sponsored pivotal trials for SPINRAZA did not include adults with SMA.

One of the largest real-world studies of SMA Type 3 to date included 103 adults3

Positive trends toward improvement in patients with SMA Type 2, even though improvements were not statistically significant

HFMSE=Hammersmith Functional Motor Scale—Expanded.

SPINRAZA improved median upper limb function and median walking distance in SMA Type 3 subgroups3

Positive trends toward improvement in patients with SMA Type 2, with a 2-point increase seen at 14 months (n=5, range 0 to 3)

RULM=Revised Upper Limb Module.

6MWT=6-Minute Walk Test.

Critical literature review and meta-analysis from Orphanet Journal of Rare Diseases1,5

Study design: A real-world, independent critical review and meta-analysis assessing the efficacy of SPINRAZA in Type 2 and Type 3 SMA patients based on 19 peer-reviewed publications:

  • Critical literature review and meta-analysis performed on structured assessments of SPINRAZA efficacy in later-onset SMA patient cohorts (all publications up to January 2021 included)
  • Subgroup analyses conducted to further verify and estimate the influence of age, SMA type, and motor function on pooled results of treated population
  • Publications containing SMA natural history outcomes were also included

Motor outcomes measured: HFMSE, RULM, and 6MWT

Study limitations:

  • Small numbers of participants in some studies and subgroups
  • Respiratory function or safety concerns were not addressed in all studies
  • Confidence intervals were often broad, and high variability observed in the cohorts required a conservative analysis of the data
  • Due to variability across the studies, a direct comparison with studies reporting data from untreated patients cannot be made
  • Other variables, such as age, SMN2 copies, or functional ability at baseline could not be analyzed due to missing data
  • This review only focused on functional motor abilities, as these were the measures most commonly used

Safety: Safety was not critically evaluated in this publication. AEs reported in individual studies are included in the publication’s Supplemental Information section. AEs were generally consistent with those seen in the SPINRAZA pivotal trials

AEs=adverse events; HFMSE=Hammersmith Functional Motor Scale—Expanded; RULM=Revised Upper Limb Module; 6MWT=6-Minute Walk Test.

Not a Biogen-sponsored study. Biogen-sponsored pivotal trials for SPINRAZA did not include adults with SMA.

Coratti et al is the largest critical literature review and meta-analysis of SPINRAZA studies to date.5

Using PRISMA guidelines—a 4-phase approach to guide the identification, screening, eligibility, and inclusion of studies into a meta-analysis—databases were searched to identify articles reporting on SPINRAZA efficacy using structured assessments in Type 2 and 3 SMA. After screening, 13 articles (out of 14,627 identified hits) were included in the meta-analysis of HFMSE results.5,7

All 13 publications in this analysis reported improved mean HFMSE scores for treated groups. Overall, treated patient cohorts had an improvement in functional motor scores as shown by the 2.27-point increase in the HFMSE pooled mean score from baseline (95% CI, 1.41-3.13).

HFMSE subgroup analysis results

Results remained consistent when studies with 10, 12, 14, or 24 months of follow-up were analyzed.

HFMSE=Hammersmith Functional Motor Scale—Expanded.

Regardless of age
group, type of later-onset SMA, or ambulatory status, patient cohorts treated with SPINRAZA experienced increased pooled mean HFMSE scores.5