MAINTAINING MOTOR FUNCTION
Individuals with later-onset (Types 2 and 3) maintained various improvements in motor function both at 15 months and after nearly 3 years of treatment
Improving motor function early on
SPINRAZA was evaluated over 15 months in CHERISH, a well-controlled clinical study of later-onset (Types 2 and 3) SMA with 126 nonambulatory individuals from 2 to 9 years old.
Individuals were randomized 2:1 to either SPINRAZA (n=84) or untreated groups (n=42). The dosing schedule in CHERISH differed from the approved regimen for SPINRAZA.
Motor skills such as sitting, rolling, and arm strength were measured by physical assessments that included the Hammersmith Functional Motor Scale—Expanded (HFMSE) and Revised Upper Limb Module (RULM) physical assessments.
Change in HFMSE score over
Individuals treated with SPINRAZA showed significant motor function improvements, with a 3.9-point increase in the HFMSE compared with the 1.0-point decline of those who were untreated.
All untreated individuals with SMA experience a progressive loss of motor function over time, regardless of age or disease severity. When treated with SPINRAZA, some individuals showed improvements in motor function compared with the progressive decline observed in those who were untreated.
Maintaining motor function over time
The long-term effects of SPINRAZA were evaluated in CS2/CS12 over a 3-year period (1050 days) in 28 individuals with later-onset (Types 2 and 3) SMA ranging from 2 to 16 years old at the time of first dose.
Individuals maintained improvements in motor function that were measured by assessments that included the HFMSE, Upper Limb Module (ULM), and 6-Minute Walk Test (6MWT).
This was an open-label study and all individuals received SPINRAZA. Limitations included differences in dosing compared with the approved regimen and the lack of an untreated group.
Change in HFMSE score over nearly 3 years
Individuals taking SPINRAZA continued to improve or maintain motor function over nearly 3 years, regardless of their level of function before starting treatment (baseline).
The Hammersmith Functional Motor Scale—Expanded (HFMSE)
The HFMSE assesses motor function of individuals older than 24 months of age.
It measures 33 items grouped into 7 categories:
- Each item is scored from 0 to 2
- The maximum score is 66
Improving upper limb function
Upper limb function and strength were evaluated using 2 different assessments: the Revised Upper Limb Module (RULM) and the Upper Limb Module (ULM).
The ULM is intended for nonambulatory individuals, while the RULM is designed for a broader range of both ambulatory and nonambulatory individuals.
Change in RULM score over
Individuals treated with SPINRAZA showed greater improvements in upper limb function as early as 3 months, with a 4.2-point increase at the end of the study compared with a 0.5-point increase in those who were untreated.
The Revised Upper Limb Module (RULM)
The RULM is a revised version of the ULM with a few additional tasks, such as bringing both arms above the head and lifting weighed objects. While the ULM is only suitable for nonambulatory individuals, the RULM can assess upper limb function in a broader range of individuals, from weaker nonambulatory to stronger ambulatory individuals.
The RULM is scored from 0 to 37 points, with higher scores indicting better function.
Change in ULM score over nearly
Improvements in upper limb function seen over 15 months in the CHERISH study are further supported by the long-term CS2/CS12 studies.
Over the course of nearly 3 years (1050 days), 6 individuals with Type 2 SMA treated with SPINRAZA reached an average ULM score of 16.5, which is just 1.5 points below the maximum score of 18.
The Upper Limb Module (ULM)
The ULM includes 9 tasks that reflect activities of daily living and can typically be performed in a brief amount of time (5 to 10 minutes) using common equipment. Activities include:
Using a pencil
Picking up a coin and placing it in a cup
Pressing a button to turn on a lamp
Lifting a beverage can to drink
Lifting a weight and moving it from circle to circle on a preprinted paper
Removing a lid from a plastic container
One of my favorite activities is writing. I think a lot of people forget how physical writing is. The ability to hold a pen in a particular way that it needs to be held—to be able to write dark enough for you to actually be able to go back and read it.
My friends and I are spread out all across the country and even though we’re talking or texting to each other every day on the phone, we still love to write letters. Nobody writes letters anymore. I would never want to lose my ability to write.
Improving walking ability
The 6-Minute Walk Test (6MWT) was used to evaluate the walking ability and endurance of ambulatory individuals with later-onset SMA. 100% of individuals treated with SPINRAZA (7/7) for at least 1050 days achieved a significant improvement in their ability to walk.
Changes in 6MWT over nearly 3 years
1 of 11 INDIVIDUALS
with Type 2 SMA gained the ability to walk independently
2 of 4 INDIVIDUALS
with Type 3 SMA regained the ability to walk independently
The achievement of this milestone in individuals with Type 2 SMA is inconsistent with the natural history of the disease, as those with Type 2 SMA are typically unable to walk independently.
The 6-Minute Walk Test (6MWT)
The 6MWT measures the distance an individual can walk in 6 minutes. Individuals are instructed to walk as far as possible along a 25-meter course and return in the opposite direction. The course is repeated as often as possible for 6 minutes.