Established safety profile in adults, children, and infants with SMA1,12,28

Established safety profile in adults, children, and infants with SMA1,12,28

 Patients living with SMA
SUNFISH PART 2
Adverse reactions occurring in ≥5% of adults and children receiving Evrysdi and with an incidence of ≥5% compared with placebo (N=180)1,2
  Evrysdi
(n=120)
Placebo
(n=60)
Adverse reaction
Fever* 22% 17%
Diarrhea 17% 8%
Rash 17% 2%
Mouth and aphthous ulcers 7% 0%
Arthralgia 5% 0%
Urinary tract infection 5% 0%

As of clinical cut-off date: September 6, 2019.

  • The most common adverse reactions reported in ≥10% of adults and children receiving Evrysdi and at an incidence greater than placebo were fever, diarrhea, and rash1

*Includes pyrexia and hyperpyrexia.
Includes rash, erythema, rash maculopapular, rash erythematous, rash papular, dermatitis allergic, and folliculitis.
Includes urinary tract infection and cystitis

  • Initial safety findings from JEWELFISH have been consistent with the safety findings in FIREFISH and SUNFISH12
    • The trial includes participants who were previously treated with investigational or approved SMA therapies12

 As of clinical cut-off date: July 31, 2020.

SUNFISH PART 2
Safety observations over 36 months2
  Placebo
0-12 months
(n=60)*
Evrysdi
0-12 months
(n=120)
Evrysdi
12-24 months
(n=120)
Evrysdi
24-36 months
(n=120)
Most common adverse events, % (n)
Upper respiratory tract infection 30.0%(18) 31.7% (38) 15.8% (19) 8.3% (10)
Cold 25.0% (15) 25.8% (31) 21.7% (26) 8.3%(10)
Fever 16.7% (10) 20.8% (25) 13.3% (16) 9.2% (11)
Headache 16.7% (10) 20.0% (24) 10.0% (12) 6.7% (8)
Diarrhea 8.3% (5) 16.7% (20) 7.5% (9) 5.8% (7)
Vomiting 23.3% (14) 14.2% (17) 11.7% (14) 6.7% (8)
Cough 20.0% (12) 14.2% (17) 10.0% (12) 4.2% (5)
Most common serious adverse events, % (n)
Pneumonia 1.7% (1) 7.5% (9) 6.7% (8) 2.5% (3)
Influenza 0% (0) 1.7% (2) 0.8% (1) 0% (0)

Clinical cut-off date for Evrysdi 0-12 months and placebo 0-12 months: September 6, 2019.
Clinical cut-off date for Evrysdi 12-24 months: September 30, 2020.
Clinical cut-off date for Evrysdi 24-36 months: September 6, 2021.
*Patients in the placebo arm received placebo for 12 months followed by Evrysdi. The patients who started in the placebo group and switched to Evrysdi are not included in the 12- to 24-month and 24- to 36-month data.
One patient withdrew from the trial after the clinical cut-off date because of an adverse event (transaminitis) that was initially reported as related to Evrysdi, and then reassessed after discontinuation as unrelated to Evrysdi.
Adverse reactions have an assumed causality to drug treatment under appropriate use; adverse events include any untoward event associated with the use of a drug, regardless of causality.

  •  No treatment-related adverse events leading to withdrawal or treatment discontinuation over 36 months29

The most common adverse reactions* to Evrysdi in infantile-onset SMA with an incidence of at least 10% were fever, diarrhea, rash, upper respiratory tract infection (including nasopharyngitis, rhinitis), lower respiratory tract infection (including pneumonia, bronchitis), constipation, vomiting, and cough1

FIREFISH PART 1 AND PART 2

Adverse events* occurring in ≥10% of infants receiving Evrysdi (N=62)2
All-patient cohort (N=62)

  Evrysdi
(N-62)
Adverse event
Upper respiratory tract infection (URTI) 82%
Pyrexia 55%
Lower respiratory tract infections (LRTI) 53%
Rash§ 29%
Constipation 26%
Diarrhea 19%
Vomiting 18%
Cough 13%
Teething 13%

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

*Adverse reactions have an assumed causality to drug treatment; adverse events include any untoward event associated with the use of a drug, regardless of causality.
URTI includes COVID-19, influenza, nasopharyngitis, pharyngitis, respiratory tract infection, respiratory tract infection viral, rhinitis, upper respiratory tract infection, upper respiratory tract infection bacterial, viral upper respiratory tract infection.
LRTI includes bronchiolitis, bronchitis, COVID-19, lower respiratory tract infection, lower respiratory tract infection viral, pneumonia, pneumonia aspiration, pneumonia bacterial, pneumonia staphylococcal, pneumonia viral, respiratory syncytial virus bronchiolitis, tracheitis, tracheobronchitis.
§Rash includes rash, dermatitis, dermatitis acneiform, dermatitis allergic, erythema, folliculitis, rash maculopapular, rash papular.

  • No treatment-related adverse events leading to treatment discontinuation over 24 months27

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

  • Initial safety findings from JEWELFISH have been consistent with the safety findings in FIREFISH and SUNFISH12
RAINBOWFISH
  • 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
  • Adverse events observed in presymptomatic SMA were consistent with those observed in infantile-onset and later-onset SMA1
  • No treatment-related adverse events leading to discontinuation

As of clinical cut-off date: July, 2021.

Most common adverse events* (reported in ≥3 infants)28
  Evrysdi
(n=18)
Adverse events, % (n)
Teething 33% (6)
Nasal congestion 28% (5)
Pyrexia 28% (5)
Diarrhea 22% (4)
Viral infection 22% (4)
Vomiting 22% (4)
Constipation 17% (3)
Cough 17% (3)
Eczema 17% (3)

As of clinical cut-off date: July 1, 2021

  • Multiple occurrences of the same adverse event in an individual are counted only once
  • Includes adverse events with onset from first dose to the cut-off date

*Adverse reactions have an assumed causality to drug treatment under appropriate use; adverse events include any untoward event associated with the use of a drug, regardless of causality.

PREVIOUS TREATMENT
  RG7800*
(MOONFISH)(n=13)
Nusinersen
(n=76)
Olesoxime*
(n=70)
Onasemnogene abeparvovec
(n=14)
All patients
(N=173)
Adverse events occurring in ≥8% of patients, % (n)
Upper respiratory tract infection 0 18% (14) 20% (14) 14% (2) 17% (30)
Pyrexia 8% (1) 22% (17) 11% (8) 29% (4) 17% (30)
Headache 8% (1) 20% (15) 17% (12) 0 16% (28)
Nausea 0 18% (14) 7% (5) 7% (1) 12% (20)
Diarrhea 0 18% (14) 6% (4) 7% (1) 11% (19)
Nasopharyngitis 15% (2) 9% (7) 9% (6) 14% (2) 10% (17)
Vomiting 8% (1) 7% (5) 9% (6) 14% (2) 8% (14)
Serious adverse events occurring in >2% of patients, % (n)
Pneumonia 0 3% (2) 1% (1) 7% (1) 2% (4)
Lower respiratory tract infection 0 1% (1) 3% (2) 0 2% (3)
Upper respiratory tract infection 0 4% (3) 0 0 2% (3)
Respiratory failure 0 4% (3) 0 0 2% (3)

As of clinical cut-off date: January 29, 2021.
*Investigational therapies; not approved by FDA for any use.
One patient withdrew from the study at baseline; therefore, 173 patients received Evrysdi.
Multiple occurrences of the same adverse event in one individual are counted only once.

FDA=Food and Drug Administration.

 

  • Evrysdi treatment duration in months, median (range):  15.2 (0.9-47.0)
  • As follow-up duration is different between groups, the overall rate of adverse events and serious adverse events cannot be compared
  • Initial safety findings from JEWELFISH have been consistent with the safety findings in FIREFISH and SUNFISH
Connect with a Genentech representative

Connect with a Genentech representative

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.

 

 

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

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

    • Data on file. Genentech USA, Inc.

      Data on file. Genentech USA, Inc.

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