For Patients and Caregivers

Results in infantile-onset SMA: infants as young as 2 months

Results in infantile-onset SMA: infants as young as 2 months

Infant patients

FIREFISH is a 2-part, open-label trial in infantile-onset spinal muscular atrophy (SMA) studying the safety and efficacy of Evrysdi in 62 infants 2 to 7 months old with Type 1 SMA. Part 1 determined the recommended dose (N=21). Part 2 assessed the efficacy and safety of Evrysdi (N=41). A pooled analysis of 58 infants aged 2 to 7 months received the  recommended dose of Evrysdi in Parts 1 and 2. Infants reflected those seen in a real-world setting, including age, disease progression, baseline motor function, and levels of disease severity.1,14

Trial design

Changing the course of SMA1

Infants receiving Evrysdi exceeded expectations for development vs those not on treatment

FIREFISH

SITTING ABILITY
as measured by BSID-III, Item 22
Recommended dose

Infant sitting up
PART 2 (PRIMARY ENDPOINT)

AFTER 12 MONTHS OF TREATMENT

29% of infants

of infants (12/41) were sitting without support for ≥5 seconds
 

PARTS 1 AND 2 (POOLED ANALYSIS)

AFTER 12 MONTHS OF TREATMENT

33% of infants

of infants (19/58) were sitting without support for ≥5 seconds
 

AFTER 24 MONTHS OF TREATMENT

60% of infants

of infants (35/58) were sitting without support for ≥5 seconds

These results indicate a clinically meaningful difference. Based on the natural history of untreated infantile-onset SMA, patients would not be expected to attain the ability to sit independently1
These results indicate a clinically meaningful difference. Based on the natural history of untreated infantile-onset SMA, patients would not be expected to attain the ability to sit independently1

BSID-III=Bayley Scales of Infant and Toddler Development–Third Edition.

Remarkable achievement of key milestones1

FIREFISH PARTS 1 AND 2 (POOLED ANALYSIS)

MOTOR MILESTONES AFTER 24 MONTHS OF TREATMENT
Recommended-dose cohort

Infant sitting up
40% of infants

of infants (23/58) were sitting without support for ≥30 seconds, as measured by BSID-III, Item 26

Able to stand image
28% of infants

of infants (16/58) were able to stand, as measured by HINE-2

  • 9/58 could stand supporting weight
  • 7/58 could stand with support

BSID-III=Bayley Scales of Infant and Toddler Development–Third Edition; HINE-2=Hammersmith Infant Neurological Examination–Module 2.

  • The Bayley Scales of Infant and Toddler Development–Third Edition (BSID-III) gross motor scale measures achievement of sitting, including Item 22, and other developmental movements in infants26
  • Items are scored as either 0 (unable) to 1 (able) compared with the abilities of healthy children26

The Hammersmith Infant Neurological Examination–Module 2 (HINE-2) assesses 8 developmental milestones for infants, including head control, sitting, voluntary grasp, ability to kick, rolling, crawling, standing, and walking.

Evrsydi prolonged survival1

FIREFISH PARTS 1 AND 2 (POOLED ANALYSIS)

All-patients cohort (N=62)*

Breath without permanent support

AFTER 12 MONTHS OF TREATMENT

87% of infants

of infants (54/62) were alive without permanent ventilation†
 

AFTER 24 MONTHS OF TREATMENT

84% of infants

of infants (52/62) were alive without permanent ventilation†

Based on the natural history of untreated infantile-onset SMA, no more than 25% of these infants would be expected to reach ≥14 months of age without permanent ventilation1
Based on the natural history of untreated infantile-onset SMA, no more than 25% of these infants would be expected to reach ≥14 months of age without permanent ventilation1

*All-patients cohort, dose adjusted per protocol. Intent-to-treat population.

†Defined as requiring a tracheostomy or >21 consecutive days of either noninvasive ventilation (≥16 hours per day) or intubation, in the absence of an acute reversible event.

FIREFISH PARTS 1 AND 2 (POOLED ANALYSIS)

84% of infants were estimated event-free after 24 months of treatment2*†
All-patients cohort (N=62)

24 months of treatment in infants chart

*Defined as alive with no permanent ventilation.

Permanent ventilation is defined as requiring a tracheostomy or >21 consecutive days of either noninvasive ventilation (≥16 hours per day) or intubation, in the absence of an acute reversible event.

†Six infants died (4 within the first 3 months following study enrollment) and one additional patient withdrew from treatment and died 3.5 months later. Four patients required permanent ventilation by month 24.

‡Two patients were censored because they attended the month 24 visit early, one patient was censored after discontinuing treatment and died 3.5 months later.

As of clinical cut-off date: November 12, 2020.

EXPLORATORY ASSESSMENTS SUGGEST

Infants taking Evrysdi had better feeding and swallowing abilities compared with natural history12*

FIREFISH PARTS 1 AND 2 (POOLED ANALYSIS)

Of infants alive taking the recommended dose (n=52)†

AFTER 24 MONTHS OF TREATMENT11

of infants (48/52) were able to feed orally‡

of infants (50/52) were able to swallow

As of clinical cut-off date: November 12, 2020.

Based on the natural history of untreated infantile-onset SMA, 87% of infants typically require feeding support by 18 months old12

Feeding and swallowing assessments should be interpreted with caution, as these are exploratory data.

*Assessed using nutritional status interview of the parent/caregiver and a standard swallowing assessment based on local practice and performed by a qualified individual. Swallowing assessment was completed at baseline and during follow-up visits. Ability of the patient to swallow age-appropriate foods was assessed. Clinical cut-off date for the 12-month data: November 14, 2019; clinical cut-off date for 24-month data: November 12, 2020.
†Data are available for only 52 infants in FIREFISH Parts 1 (Cohort B, n=17) and 2 (n=41) because of 6 infant deaths prior to the time of the assessment. One infant died approximately 3.5 months after discontinuing treatment.
‡Includes infants who were able to feed orally or in combination with a feeding tube.

Jewelfish trial icon
Learn more about JEWELFISH, an open-label safety trial including adults, children, and infants taking Evrysdi who have received previous treatment with approved or investigational therapies.30
Trial design
Safety
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Important Safety Information and Indication

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
  • There is a pregnancy exposure registry that monitors pregnancy and fetal/neonatal/infant outcomes in women exposed to Evrysdi during pregnancy. Physicians are encouraged to register patients and pregnant women are encouraged to register themselves by calling 1-833-760-1098 or visiting www.evrysdipregnancyregistry.com
  • 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.

 

 

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

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