Achieved meaningful results across
age
groups—from infants to
adults^1-3

Study design: An independent, prospective, observational study that assessed 237 adult and teen patients with genetically-confirmed 5q-associated SMA who were treated with SPINRAZA (12 mg) for up to 38 months. Patients from the SMArtCARE registry were recruited between July 2017 and May 2022 in Germany, Switzerland, and Austria. Thirty-one patients were excluded due to insufficient follow-up and 11 discontinued SPINRAZA before completing the 14-month follow-up. Patients with missing data points were excluded from analysis.³

Please refer to the FDA-approved dosing schedule in the US Prescribing Information.

Study limitations³:

Endpoints: Three functional outcomes were assessed at 14, 26, and 38 months of treatment and included 237, 171, and 120 patients, respectively³:

• HFMSE
   
  • Primary endpoint: Mean change vs baseline
  • Clinically meaningful improvement (defined as a change of ≥3 points)
• RULM
   
  • Mean change vs baseline
  • Clinically meaningful improvement (defined as a change of ≥2 points)
• 6-Minute Walk Test (6MWT) in ambulatory patients
   
  • Mean change vs baseline
  • Clinically meaningful improvement (increase in walking distance by ≥30 meters)

Safety: The safety was generally consistent with the known safety of SPINRAZA in clinical trials.^1,3,8

• Safety was evaluated in 389 patients screened who had received at least one injection³
   
  • 732 adverse drug reactions or procedure-related complications were documented in 91% of patients (n=353/389)
  • 26% of patients (n=103/389) reported no adverse drug reactions; 64% of patients (n=250/389) reported at least 1 adverse reaction
  • Most adverse reactions were post-lumbar puncture syndrome, headache, back pain, and infections

This registry was funded in part by Biogen.
6MWT, 6-minute walk test; FDA, Food and Drug Administration; HFMSE, Hammersmith Functional Motor Scale–Expanded; RULM, Revised Upper Limb Module; SMA, spinal muscular atrophy.

Long-term outcomes with SPINRAZA:
HFMSE, RULM, and 6MWT³

Improvement in mean HFMSE score vs baseline at each assessment³

Primary endpoint: Change in HFMSE score from baseline

*At baseline 2 patients had a full score (66 points) and 55 patients scored 0 points.

Proportion of patients with clinically meaningful change in HFMSE score vs baseline up to 38 months

28 of the 68 patients with clinically meaningful improvement at 14 months maintained this improvement for ≥38 months³

• HFMSE interpretation may have been limited by floor effects; non-ambulatory patients could not perform some of the activities assessed by HFMSE, leading to lower achievable scores

6MWT, 6-minute walk test; Cl, confidence interval; HFMSE, Hammersmith Functional Motor Scale–Expanded; RULM, Revised Upper Limb Module; SD, standard deviation.

RULM scores improved from baseline at each assessment³

Mean improvement in RULM from baseline

^†At baseline 74 patients had a full score (37 points) and 17 patients scored 0 points.

Proportion of patients with clinically meaningful change in RULM score vs baseline up to 38 months

37% of patients (n=25/68) with clinically meaningful increase in RULM score at 14 months maintained this improvement at 38 months³

• RULM interpretation in ambulatory patients may have been limited by ceiling effects, which may have affected the results of the study

Cl, confidence interval; RULM, Revised Upper Limb Module; SD, standard deviation.

Improvement in mean walking distance from baseline in the 6MWT at each assessment in ambulatory patients³

Mean improvement in walking distance (in meters) from baseline

Proportion of patients with clinically meaningful change in 6MWT score vs baseline up to 38 months

At 38 months, the mean improvement in walking distance in the 6MWT from baseline was 32.20 meters³

6MWT, 6-minute walk test; Cl, confidence interval; SD, standard deviation.

Exploratory subgroup analysis in ambulatory and non-ambulatory patients^3‡

Mean improvement in HFMSE and RULM score from baseline

Regardless of ambulatory status, improvement in mean HFMSE and RULM scores were reported with SPINRAZA³

• HFMSE score interpretation in non-ambulatory patients may have been limited by floor effects; non-ambulatory patients could not perform some of the activities assessed by HFMSE, leading to lower achievable scores. RULM score interpretation in ambulatory patients may have been limited by ceiling effects, which may have affected the results of the study

^‡Additional subgroups were reported in the study.

CI, confidence interval; HFMSE, Hammersmith Functional Motor Scale–Expanded; RULM, Revised Upper Limb Module; SD, standard deviation; SMA, spinal muscular atrophy.

Long-term outcomes with SPINRAZA: This real-world evidence informs on the safety and efficacy of long-term SPINRAZA treatment for up to 38 months in adults and teens with SMA³

In this real-world study, there were 1,023 intrathecal administrations and no administration failures²

6MWT, 6-minute walk test; CHOP INTEND, Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders; COVID-19, coronavirus disease 2019; CT, computed tomography; HFMSE, Hammersmith Functional Motor Scale—Expanded; PGI-I, Patient Global Impression-Improvement; PLPS, post-lumbar puncture syndrome; RULM, revised upper limb module; SMA, spinal muscular atrophy.

In the observational study, mean HFMSE score improved compared with baseline at each time point²

HFMSE patient population (n=73*):

RESULTS:

• Mean HFMSE score increase of 5.1 points at month 30 (n=28)

Mean change in HFMSE vs baseline up to 30 months

In the study, a ≥3-point improvement was considered a clinically meaningful change

Proportion of patients who showed improvement, no change, or decline in HFMSE score vs baseline up to 30 months

• In 15% of patients (11/73), the HFMSE score improved by ≥10 points during the study

*One patient with SMA type 2 did not undergo assessment at day 180 (month 6) but was assessed at the subsequent 4 time points. Therefore, he was included in the analysis. At month 30, 28 patients were evaluated using the HFMSE.

HFMSE, Hammersmith Functional Motor Scale—Expanded; SD, standard deviation; SMA, spinal muscular atrophy.

At month 30, the HFMSE score showed improvement or no change in 96% of patients (27/28) on treatment with SPINRAZA²

Mean CHOP INTEND score improved compared with baseline at each time point²

CHOP INTEND patient population (n=47^† ):

RESULTS:

• Mean CHOP INTEND score increased by 5.6 points at month 26 vs baseline
• Clinically meaningful improvements (≥4 points) in the CHOP INTEND score were seen in 20.5% of patients (9/44) at month 6 and in 65% of patients (11/17) at month 26

Mean change in CHOP INTEND score between month 0 and month 26^§

• 5 patients were available for assessment at month 30; the mean difference was 9.4 points

The CHOP-ATTEND test validated for adult patients with severe symptoms was not available at the time of the study. For this reason, the CHOP INTEND test, which is not validated in adults, was used.

^† Forty-four patients were assessed at least twice (at month 0 and month 6).

^‡Baseline CHOP INTEND score was not available for 3 adults with SMA Type 1 who started treatment abroad within the Expanded Access Program (EAP). They started study evaluation at month 10, month 14, and month 18, respectively. Assessment was available up to month 30 for 2 of these patients.

^§Low patient numbers (n=5) at 30 months preclude meaningful interpretation at this time point.

CHOP-ATTEND, Children’s Hospital of Philadelphia Adult Test of Neuromuscular Disorders; CHOP INTEND, Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders; EAP, Expanded Access Program; SD, standard deviation; SMA, spinal muscular atrophy.

94% of patients (16/17) noted improvement by at least 1 point at month 26 vs baseline²

RULM score improved compared with baseline at each time point²

RULM patient population (n=51):

RESULTS:

• Mean RULM score increased by 1.96 points at month 30 vs baseline

Mean change in RULM score vs baseline up to 30 months

Proportion of patients who showed improvement, no change, or decline in RULM vs baseline up to 30 months

 
 
• During treatment, the proportion of patients who showed improvement in upper limb function was 61% (14/23) at month 30

RULM, Revised Upper Limb Module; SD, standard deviation; SMA, spinal muscular atrophy.

Clinically meaningful improvements (≥2 points) in RULM score was seen in 43.5% (10/23) of patients at month 30²

Mean 6MWT scores improved at each time point²

6MWT patient population (n=27 ^||):

• Mean age: 27 years (SD, 13; range, 6-59 years)
• Mean disease duration: 18 years (SD, 10; range, 4-33 years)
• SMA type 3: 27 patients

RESULTS:

• Mean 6MWT improved by 27.0 meters at month 30 vs baseline

Mean change in 6MWT vs baseline up to 30 months

Proportion of patients who showed improvement, no change, or decline in 6MWT score vs baseline up to 30 months

• A relatively large number of patients experienced worsening in each point of treatment: 40% of patients (6/15) at month 6 and 33% of patients (4/12) at month 30

^||The lack of a fairly significant number of ratings in the 6MWT was mainly due to patients’ fear of staying too long in the hospital and contacting medical staff and other patients during the pandemic.

6MWT, 6-minute walk test; SD, standard deviation; SMA, spinal muscular atrophy.

Clinically meaningful improvement (≥30 meters increase in walking distance) was observed in 33% of patients (5/15) at month 6 and was 50% (6/12) at month 30²

Improvements were seen across all functional assessments up to 30 months²

Distribution of patients who achieved a clinically meaningful improvement in each of the functional tests

 
 
• Clinically meaningful improvement was defined as a change in HFMSE score of ≥3 points, change in CHOP INTEND score of ≥4 points, and change in RULM score of ≥2 points. For patients able to walk independently, significant improvement in the 6MWT score was defined as an increase in walking distance by at least 30 meters

^¶Three patients who did not undergo assessment at month 0 were excluded. Only 5 patients were evaluated for CHOP INTEND at month 30.

Patients and caregivers assessed and self-reported their status, and most reported improvement or stabilization while on treatment^2#

• While no patients reported feeling much worse or very much worse at each time point, between 2 and 5 patients reported feeling minimally worse at various time points during the study

^#PGI-I data was subjective and patient-reported.

6MWT, 6-minute walk test; CHOP INTEND, Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders; HFMSE, Hammersmith Functional Motor Scale—Expanded; PGI-I, Patient Global Impression–Improvement; RULM, Revised Upper Limb module; SD, standard deviation.

After 26 months of SPINRAZA treatment, 96.5% of patients (62/64) reported subjective improvement or stabilization/no change, which was also reported at month 30 in 100% (47/47) of the patients²

6MWT, 6-minute walk test; AE, adverse event; HFMSE, Hammersmith Functional Motor Scale—Expanded; RULM, Revised Upper Limb Module; SMA, spinal muscular atrophy.

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 65^5,6

Primary endpoint: Mean change from baseline in HFMSE score (95% CI)*

Fourteen 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.

*Lower bound 95% CI not shown.

^†Exploratory endpoint.

A ≥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.^5,7

CI, confidence interval; HFMSE, Hammersmith Functional Motor Scale—Expanded; SMA, spinal muscular atrophy.

SPINRAZA improved mean upper limb function and walking distance compared with baseline at every study time point⁵

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

^‡Lower bound of 95% CI not shown.

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

CI, confidence interval; RULM, Revised Upper Limb Module.

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

^||Lower bound of 95% CI not shown.

6MWT, 6-minute walk test; CI, confidence interval.