For Patients and Caregivers

Results in later-onset SMA: adults and children

Results in later-onset SMA: adults and children

Jim, living with Type 3 SMA

Adults and children significantly improved their motor skills and upper limb function when taking Evrysdi, an at-home treatment1

SUNFISH is a 2-part, randomized, placebo-controlled trial in patients 2 to 25 years of age with later-onset spinal muscular atrophy (SMA): the first placebo-controlled trial in adults and children older than 9 years with SMA. Purposely designed to include older adults and children with complications, such as contractures and severe scoliosis, participants reflected the real-world SMA population.1,2

Trial design

Evrysdi significantly improved or maintained motor skills1

WITH EVRYSDI, PARTICIPANTS EXPERIENCED A SIGNIFICANTLY GREATER CHANGE IN MOTOR FUNCTION SCORE VS PLACEBO, AS MEASURED BY MFM-321

SUNFISH PART 2

Change in MFM-32 score over 12 months of treatment*†

Change in motor function score over 12 months chart
  • 1.55-point difference (95% CI: 0.30, 2.81) between the means (P=0.0156)
These results demonstrated a clinically meaningful difference for adults and children treated with Evrysdi compared with placebo1
These results demonstrated a clinically meaningful difference for adults and children treated with Evrysdi compared with placebo1

*The least square (LS) mean difference for change from baseline in MFM-32 score (95% CI).
†Based on the missing-data rule for MFM-32, 6 patients (n=5 for Evrysdi; n=1 for placebo) were excluded from the analysis.

MFM-32=Motor Function Measure-32 Items.

THE MOTOR FUNCTION MEASURE–32 ITEMS (MFM-32) WAS THE KEY MOTOR FUNCTION MEASURE USED IN SUNFISH

The validated, 32-item scale is designed to capture meaningful change in gross and fine motor skills among a broad range of ambulatory and nonambulatory people with SMA.

The 32 items of the MFM-32 are divided into 3 domains19,21:

Domain 1
Standing and transfers

13 total items used to identify changes in people with higher motor functions, such as:

raise pelvis image

Raise pelvis

sit up image

Sit up

Stand from or sit in chair‡

Squat or reach floor‡

Run or walk‡

Stand from floor

Balance or hop on one foot‡

Domain 2
Axial and proximal limb motor function

12 total items used to monitor a wide range of torso and limb functions, such as:

raise head image

Raise head‡

roll over image

Roll over

raise hands while seated image

Raise hands while seated‡

raise foot image

Raise foot

maintain position without image

Maintain position without upper limb support‡

place and extend arms image

Place and extend arms on table‡

Domain 3
Distal limb motor function

7 total items used to identify subtle changes in people with limited motor functions, such as:

hand image

Trace‡

flex foot image

Flex foot

tear paper image

Tear paper

pick up and hold coins image

Pick up and hold coins or tennis ball‡

draw continuous loop image

Draw continuous loops

  • Designed to precisely monitor motor abilities that correspond to important daily functions in people with neuromuscular disorders, including adults and children with SMA
  • Sensitive to small changes in motor function that translate to significant gain or loss of daily functions
  • In a natural history study of >100 people with SMA, the mean MFM-32 score was:
        ~ 40.0 for people with Type 2 disease*
        ~ 70.1 for people with Type 3 disease†

MFM-32 items are scored as follows20: 0=does not initiate movement or starting position cannot be maintained; 1=partially completes the exercise; 2=completes the exercise with compensations, slowness, or obvious clumsiness; 3=completes the exercise with a standard pattern.
*Standard deviation: 11.4 (range, 14.6-66.7).21
†Standard deviation: 18.8 (range, 14.6-93.8).21
‡Some items in this list have been consolidated for simplicity but are scored separately.

SUNFISH PART 2

Change in MFM-32 score over 24 months of treatment

Change in motor function score over 24 months chart
1.83-point mean change from baseline with Evrysdi at 24 months (95% CI: 0.74, 2.92)
These 24-month data should be interpreted with caution, as they are from a non-placebo-controlled follow-up period of the Evrysdi arm

*Patients in the placebo arm received placebo for 12 months followed by Evrysdi for 12 months. Evrysdi period not shown.
†Number of patients with an available total score (result) at respective time points. Intent-to-treat patients.
MFM-32=Motor Function Measure–32 Items.

Evrysdi enabled greater strength in hand and arm movements1

WITH EVRYSDI, PARTICIPANTS EXPERIENCED A SIGNIFICANTLY GREATER CHANGE IN UPPER LIMB FUNCTION VS PLACEBO, AS MEASURED BY RULM1,17

SUNFISH PART 2

Change in RULM score over 12 months of treatment*†

Change in RULM function score over 12 months chart
  • 1.59-point difference (95% CI: 0.55, 2.62) between the means (P=0.0469)
These results demonstrated a clinically meaningful difference for patients treated with Evrysdi compared with placebo1,17
These results demonstrated a clinically meaningful difference for patients treated with Evrysdi compared with placebo1,17

*The least square (LS) mean difference for change from baseline in RULM score (95% CI).
†Based on the missing-data rule for RULM, 3 patients (n=1 for Evrysdi; n=2 for placebo) were excluded from the analysis.

RULM=Revised Upper Limb Module.

THE REVISED UPPER LIMB MODULE (RULM) IS A THOROUGH MEASUREMENT OF UPPER LIMB FUNCTION FOR A BROAD RANGE OF PEOPLE WITH SMA

This scale assesses the ability to push, pull, place, tear, open, raise, and lift objects, as well as hand, arm, and reaching movements in adults and children.22

The RULM assessment includes 19 scorable items* such as:

pick up objects image

Pick up objects, like coins/tokens

tear paper image

Tear paper

raise cup to mouth image

Raise cup to mouth

open plastic container image

Open plastic container

  • Place coin/token into cup
  • Reach to the side and touch coin/token
  • Complete the path with pencil without stopping
  • Push button with one hand
  • Bring hands from lap to table
  • Bring hand above shoulder height (shoulder flexion)
  • Bring both arms above head (shoulder abduction)
  • Lift and move ~1/2-lb and ~1-lb weights without sliding†‡
  • Bring ~1-lb weight from lap to table or eye level†
  • Bring ~1-lb and ~2-lb weight above shoulder height (shoulder abduction, shoulder flexion)†‡
  • Specifically designed for ambulatory and nonambulatory people ≥30 months of age with SMA
  • Able to capture a wide range of upper limb mobility in people with varying degrees of muscle weakness
  • In a natural history study of >100 people with SMA, the mean RULM score was23:
    ~11 for nonsitters with Type 2 disease||
    ~15 for sitters with Type 2 disease
    ~27 for nonambulatory people with Type 3 disease#
    ~34 for ambulatory people with Type 3 disease**

Nineteen RULM items are scored§ as follows22: 0=unable; 1=able with modification; 2=able without difficulty.
*The RULM includes 20 items, 19 can be scored. (There is an entry item that serves as functional class identification and does not contribute to the total score.)
†Weight is approximate and has been converted from grams to pounds; ~1/2 lb=200 g, ~1 lb=500 g, and ~2 lb=1 kg.
‡Some items in this list have been consolidated for simplicity but are scored separately.
§Of the 19 items, 18 tasks are scored from 0 to 2, while 1 item is scored from 0 to 1.
||Standard deviation: 6.85 (range, 0.0-17.0).
Standard deviation: 6.52 (range, 1.0-28.0).
#Standard deviation: 6.89 (range, 10.0-37.0).
**Standard deviation: 3.73 (range, 22.0-37.0).

SUNFISH PART 2

Change in RULM score over 24 months of treatment

Change in RULM function score over 24 months chart
2.79-point mean change from baseline with Evrysdi at 24 months (95% CI: 1.94, 3.64)
These 24-month data should be interpreted with caution, as they are from a non-placebo-controlled follow-up period of the Evrysdi arm

*Patients in the placebo arm received placebo for 12 months followed by Evrysdi for 12 months. Evrysdi period not shown.
†Number of patients with an available total score (result) at respective time points. Intent-to-treat patients.
RULM=Revised Upper Limb Module.

Jewelfish trial icon
Learn more about JEWELFISH, an ongoing, open-label safety trial including adults, children, and infants taking Evrysdi who have received previous treatment with approved or investigational therapies.12
Trial design
Safety
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Indication

Evrysdi is indicated for the treatment of spinal muscular atrophy (SMA) in pediatric and adult patients.

 

Interactions with Substrates of MATE Transporters

  • Based on in vitro data, Evrysdi may increase plasma concentrations of drugs eliminated via MATE1 or MATE2-K, such as metformin
  • Avoid coadministration of Evrysdi with MATE (multidrug and toxin extrusion) substrates. If coadministration cannot be avoided, monitor for drug-related toxicities and consider dosage reduction of the coadministered drug if needed

Pregnancy & Breastfeeding

  • Evrysdi may cause embryofetal harm when administered to a pregnant woman. In animal studies, administration of Evrysdi during pregnancy and/or lactation resulted in adverse effects on development. Advise pregnant women of the potential risk to the fetus
  • Pregnancy testing is recommended prior to initiating Evrysdi. Advise female patients to use contraception during treatment with Evrysdi and for at least 1 month after the last dose
  • The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Evrysdi and any potential adverse effects on the breastfed infant

Potential Effects on Male Fertility

  • Counsel male patients that fertility may be compromised by treatment with Evrysdi. Male patients may consider sperm preservation prior to treatment

Most Common Adverse Reactions

  • The most common adverse reactions in later-onset SMA (incidence in at least 10% of patients treated with Evrysdi and more frequent than control) were fever, diarrhea, and rash
  • The most common adverse reactions in infantile-onset SMA were similar to those observed in later-onset SMA patients. Additionally, adverse reactions with an incidence of at least 10% were upper respiratory tract infection (including nasopharyngitis, rhinitis), lower respiratory tract infection (including pneumonia, bronchitis), constipation, vomiting, and cough
  • The safety profile for presymptomatic patients is consistent with the safety profile for symptomatic SMA patients treated with Evrysdi in clinical trials

You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at 1-888-835-2555.

Please see full Prescribing Information for additional Important Safety Information.

 

 

    • Evrysdi® (risdiplam) Prescribing Information. Genentech, Inc.

      Evrysdi® (risdiplam) Prescribing Information. Genentech, Inc.

    • Data on file. Genentech USA, Inc.

      Data on file. Genentech USA, Inc.

    • NIH US National Library of Medicine. Spinal muscular atrophy. https://ghr.nlm.nih.gov/condition/spinal-muscular-atrophy. Accessed June 7, 2021.

      NIH US National Library of Medicine. Spinal muscular atrophy. https://ghr.nlm.nih.gov/condition/spinal-muscular-atrophy. Accessed June 7, 2021.

    • Farrar MA, Park SB, Vucic S, et al. Emerging therapies and challenges in spinal muscular atrophy. Ann Neurol. 2017;81(3):355-368.

      Farrar MA, Park SB, Vucic S, et al. Emerging therapies and challenges in spinal muscular atrophy. Ann Neurol. 2017;81(3):355-368.

    • Sumner CJ, Crawford TO. Two breakthrough gene-targeted treatments for spinal muscular atrophy: challenges remain. J Clin Invest. 2018;128(8):3219-3227.

      Sumner CJ, Crawford TO. Two breakthrough gene-targeted treatments for spinal muscular atrophy: challenges remain. J Clin Invest. 2018;128(8):3219-3227.

    • CureSMA. Voice of the patient report: spinal muscular atrophy (SMA). https://curesma.wpengine.com/wp-content/uploads/2018/01/SMA-VoP-for-publication-1-22-2018.pdf. Published January 10, 2018. Accessed June 7, 2021.

      CureSMA. Voice of the patient report: spinal muscular atrophy (SMA). https://curesma.wpengine.com/wp-content/uploads/2018/01/SMA-VoP-for-publication-1-22-2018.pdf. Published January 10, 2018. Accessed June 7, 2021.

    • Prior TW, Leach ME, Finanger E. Spinal Muscular Atrophy. In: Adam MP, Ardinger HH, Pagon RA, et al., eds. GeneReviews®. Seattle (WA): University of Washington, Seattle; February 24, 2000.

      Prior TW, Leach ME, Finanger E. Spinal Muscular Atrophy. In: Adam MP, Ardinger HH, Pagon RA, et al., eds. GeneReviews®. Seattle (WA): University of Washington, Seattle; February 24, 2000.

    • Hamilton G, Gillingwater TH. Spinal muscular atrophy: going beyond the motor neuron. Trends Mol Med. 2013;19(1):40-50.

      Hamilton G, Gillingwater TH. Spinal muscular atrophy: going beyond the motor neuron. Trends Mol Med. 2013;19(1):40-50.

    • Baranello G, Bloespflug-Tanguy O, Darras BT, et al. FIREFISH Part 1: 24-month safety and exploratory outcomes of risdiplam (RG7916) in infants with Type 1 spinal muscular atrophy (SMA). Supplemental presentation at: 2020 Virtual World Muscle Society; September 28-October 2, 2020; Virtual.

      Baranello G, Bloespflug-Tanguy O, Darras BT, et al. FIREFISH Part 1: 24-month safety and exploratory outcomes of risdiplam (RG7916) in infants with Type 1 spinal muscular atrophy (SMA). Supplemental presentation at: 2020 Virtual World Muscle Society; September 28-October 2, 2020; Virtual.

    • Day JW, Annoussamy M, Baranello G, et al. SUNFISH Part 1: 24-month safety and exploratory outcomes of risdiplam (RG7916) treatment in patients with Type 2 or 3 spinal muscular atrophy (SMA). Presentation at: 2020 Virtual SMA Conference; June 8-12, 2020; Virtual.

      Day JW, Annoussamy M, Baranello G, et al. SUNFISH Part 1: 24-month safety and exploratory outcomes of risdiplam (RG7916) treatment in patients with Type 2 or 3 spinal muscular atrophy (SMA). Presentation at: 2020 Virtual SMA Conference; June 8-12, 2020; Virtual.

    • Chiriboga CA, Bruno C, Duong T, et al. JEWELFISH: safety and pharmacodynamic data in non-naïve patients with spinal muscular atrophy (SMA) receiving treatment with risdiplam. Presentation at: 2020 Virtual CureSMA Conference; June 8-12, 2020; Virtual.

      Chiriboga CA, Bruno C, Duong T, et al. JEWELFISH: safety and pharmacodynamic data in non-naïve patients with spinal muscular atrophy (SMA) receiving treatment with risdiplam. Presentation at: 2020 Virtual CureSMA Conference; June 8-12, 2020; Virtual.

    • Chiriboga CA, Bruno C, Duong T, et al. JEWELFISH: safety and pharmacodynamic data in non-naïve patients with spinal muscular atrophy (SMA) receiving treatment with risdiplam. Presentation at: 2021 Virtual World Muscle Society (WMS) Conference; September 21-24, 2021; Virtual.

      Chiriboga CA, Bruno C, Duong T, et al. JEWELFISH: safety and pharmacodynamic data in non-naïve patients with spinal muscular atrophy (SMA) receiving treatment with risdiplam. Presentation at: 2021 Virtual World Muscle Society (WMS) Conference; September 21-24, 2021; Virtual.

    • Poirier A, Weetall M, Heinig K, et al. Risdiplam distributes and increases SMN protein in both the central nervous system and peripheral organs. Pharmacol Res Perspect. 2018;6(6):1-12.

      Poirier A, Weetall M, Heinig K, et al. Risdiplam distributes and increases SMN protein in both the central nervous system and peripheral organs. Pharmacol Res Perspect. 2018;6(6):1-12.

    • Baranello G, Darras BT, Day JW, et al. Risdiplam in Type 1 spinal muscular atrophy. N Engl J Med. 2021;384:915-923. doi: 10.1056/NEJMoa2009965.

      Baranello G, Darras BT, Day JW, et al. Risdiplam in Type 1 spinal muscular atrophy. N Engl J Med. 2021;384:915-923. doi: 10.1056/NEJMoa2009965.

    • Darras BT, Baranello G, Boespflug-Tanguy O, et al. FIREFISH Part 1: 24-month safety and exploratory outcomes of risdiplam in infants with Type 1 spinal muscular atrophy (SMA). Presentation at: 2021 Virtual MDA Conference; March 15-18, 2021; Virtual.

      Darras BT, Baranello G, Boespflug-Tanguy O, et al. FIREFISH Part 1: 24-month safety and exploratory outcomes of risdiplam in infants with Type 1 spinal muscular atrophy (SMA). Presentation at: 2021 Virtual MDA Conference; March 15-18, 2021; Virtual.

    • Oskoui M, Day JW, Deconinck N, et al. SUNFISH Part 2: 24-month efficacy and safety of risdiplam in patients with Type 2 or non-ambulant Type 3 spinal muscular atrophy (SMA). Presentation at: 2021 Virtual MDA Conference; March 15-18, 2021; Virtual.

      Oskoui M, Day JW, Deconinck N, et al. SUNFISH Part 2: 24-month efficacy and safety of risdiplam in patients with Type 2 or non-ambulant Type 3 spinal muscular atrophy (SMA). Presentation at: 2021 Virtual MDA Conference; March 15-18, 2021; Virtual.

    • Mercuri E, Barisic N, Boespflug-Tanguy O, et al. SUNFISH Part 2: efficacy and safety of risdiplam (RG7916) in patients with Type 2 or non-ambulant Type 3 spinal muscular atrophy (SMA). Presentation at: 2020 Virtual American Academy of Neurology (AAN) Conference; April 25-May 1, 2020; Virtual.

      Mercuri E, Barisic N, Boespflug-Tanguy O, et al. SUNFISH Part 2: efficacy and safety of risdiplam (RG7916) in patients with Type 2 or non-ambulant Type 3 spinal muscular atrophy (SMA). Presentation at: 2020 Virtual American Academy of Neurology (AAN) Conference; April 25-May 1, 2020; Virtual.

    • Clinicaltrials.gov. A study of risdiplam in infants with genetically diagnosed and presymptomatic spinal muscular atrophy (RAINBOWFISH). [NCT03779334]. https://clinicaltrials.gov/ct2/show/NCT03779334. Last update posted June 7, 2021. Accessed June 7, 2021.

      Clinicaltrials.gov. A study of risdiplam in infants with genetically diagnosed and presymptomatic spinal muscular atrophy (RAINBOWFISH). [NCT03779334]. https://clinicaltrials.gov/ct2/show/NCT03779334. Last update posted June 7, 2021. Accessed June 7, 2021.

    • Bérard C, Payan C, Hodgkinson I, et al., and the MFM Collaborative Study Group. A motor function measure scale for neuromuscular diseases. Construction and validation study. Neuromuscul Disord. 2005;15:463-470.

      Bérard C, Payan C, Hodgkinson I, et al., and the MFM Collaborative Study Group. A motor function measure scale for neuromuscular diseases. Construction and validation study. Neuromuscul Disord. 2005;15:463-470.

    • Trundell D, Le Scouiller S, Le Goff L, et al. Assessment of the validity and reliability of the 32-item Motor Function Measure in individuals with Type 2 or non-ambulant Type 3 spinal muscular atrophy. PLoS One. 2020;15(9):e0238786. doi: 10.1371/journal. pone.0238786.

      Trundell D, Le Scouiller S, Le Goff L, et al. Assessment of the validity and reliability of the 32-item Motor Function Measure in individuals with Type 2 or non-ambulant Type 3 spinal muscular atrophy. PLoS One. 2020;15(9):e0238786. doi: 10.1371/journal. pone.0238786.

    • Vuillerot C, Payan C, Iwaz J, et al. Responsiveness of the motor function measure in patients with spinal muscular atrophy. Arch Phys Med Rehabil. 2013;94(8):1555-1561.

      Vuillerot C, Payan C, Iwaz J, et al. Responsiveness of the motor function measure in patients with spinal muscular atrophy. Arch Phys Med Rehabil. 2013;94(8):1555-1561.

    • Mazzone ES, Mayhew A, Montes J, et al. Revised upper limb module for spinal muscular atrophy: development of a new module. Muscle Nerve. 2017;55:869-874.

      Mazzone ES, Mayhew A, Montes J, et al. Revised upper limb module for spinal muscular atrophy: development of a new module. Muscle Nerve. 2017;55:869-874.

    • Pera MC, Coratti G, Mazzone ES, et al. Revised upper limb module for spinal muscular atrophy: 12 month changes. Muscle Nerve. 2019;59:426-430.

      Pera MC, Coratti G, Mazzone ES, et al. Revised upper limb module for spinal muscular atrophy: 12 month changes. Muscle Nerve. 2019;59:426-430.

    • Mazzella A, Curry M, Belter L, et al. “I have SMA, SMA doesn't have me”: a qualitative snapshot into the challenges, successes, and quality of life of adolescents and young adults with SMA. Orphanet J Rare Dis. 2021;16(1):96.

      Mazzella A, Curry M, Belter L, et al. “I have SMA, SMA doesn't have me”: a qualitative snapshot into the challenges, successes, and quality of life of adolescents and young adults with SMA. Orphanet J Rare Dis. 2021;16(1):96.

    • Wan HWY, Carey KA, D’Silva A, et al. “Getting ready for the adult world”: how adults with spinal muscular atrophy perceive and experience healthcare, transition and well-being. Orphanet J Rare Dis. 2019;14(1):74.

      Wan HWY, Carey KA, D’Silva A, et al. “Getting ready for the adult world”: how adults with spinal muscular atrophy perceive and experience healthcare, transition and well-being. Orphanet J Rare Dis. 2019;14(1):74.

    • Albers CA, Grieve AJ. Test review: Bayley, N. (2006). Bayley Scales of Infant and Toddler Development–Third Edition. San Antonio, TX: Harcourt Assessment. J Psychoeduc Assess. 2007;25(2):180-198.

      Albers CA, Grieve AJ. Test review: Bayley, N. (2006). Bayley Scales of Infant and Toddler Development–Third Edition. San Antonio, TX: Harcourt Assessment. J Psychoeduc Assess. 2007;25(2):180-198.