These Highlights Do Not Include All The Information Needed To Use Evrysdi Safely And Effectively. See Full Prescribing Information For Evrysdi.

EVRYSDI for Oral Solution

In infants who are breastfed, EVRYSDI for oral solution can be administered before or after breastfeeding. EVRYSDI cannot be mixed with formula or milk.

Instruct patients or caregivers to administer the dose using the reusable oral syringe provided.

EVRYSDI for oral solution must be taken immediately after it is drawn up into the oral syringe. If EVRYSDI is not taken within 5 minutes, EVRYSDI should be discarded from the oral syringe, and a new dose should be prepared.

Instruct patients to drink water after taking EVRYSDI for oral solution to ensure the drug has been completely swallowed.

EVRYSDI for oral solution can be administered via a nasogastric or gastrostomy tube. The tube should be flushed with water after delivering EVRYSDI for oral solution [see Instructions for Use].

Storage and Handling

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Keep in the original bottle. Keep the bottle tightly closed in order to protect from moisture.

INSTRUCTIONS FOR USE

EVRYSDI^® [ev-RIZ-dee]

(risdiplam)

for oral solution

Please read and understand this Instructions for Use and the Patient Information leaflet before you start taking EVRYSDI for information about EVRYSDI and how to prepare and give EVRYSDI through an oral syringe, gastrostomy tube (G-tube), or nasogastric tube (NG-tube).

If you have any questions about how to take EVRYSDI, contact your healthcare provider.

EVRYSDI should come as a liquid in a bottle when you receive it from the pharmacy. Do not take EVRYSDI and contact your pharmacist if the medicine in the bottle is a powder.

Each EVRYSDI carton contains (see Figure A):

Important information about EVRYSDI

• Ask your healthcare provider to show you the correct oral syringe you should use and how to measure your prescribed daily dose.
• Always use the reusable oral syringes that come with EVRYSDI to measure your prescribed daily dose. If your carton does not contain two identical syringes, contact your pharmacist.
• Always take EVRYSDI exactly as your healthcare provider tells you to take it.
• Take EVRYSDI 1 time daily with or without a meal at approximately the same time each day.
• Do not take EVRYSDI if the bottle adapter is not in the bottle. If the bottle adapter is not in the bottle, contact your pharmacist.
• Do not mix EVRYSDI into food or liquids. Do not mix EVRYSDI with formula or milk.
• Do not take EVRYSDI if the bottle or oral syringes are damaged.
• Avoid getting EVRYSDI on your skin or in your eyes. If EVRYSDI gets on your skin, wash the area with soap and water. If EVRYSDI gets in your eyes, rinse your eyes with water.
• If you spill EVRYSDI, dry the area with a dry paper towel and then clean with water. Throw away the paper towel in the trash and wash your hands well with soap and water.
• If there is not enough EVRYSDI left in the bottle for your prescribed dose, throw away (discard) the bottle with remaining EVRYSDI and used oral syringes according to your local requirements.
• Use a new bottle of EVRYSDI to get your prescribed dose.
  
  Do not mix EVRYSDI from the new bottle with the bottle you are currently using.

How to store EVRYSDI

A) Preparing and withdrawing your dose

How to prepare your dose of EVRYSDI

If you are taking your dose of EVRYSDI by mouth, follow the instructions in " B) How to take a dose of EVRYSDI by mouth ".

If you are taking your dose of EVRYSDI through a gastrostomy tube, follow the instructions in " C) How to give a dose of EVRYSDI through a gastrostomy tube ".

If you are taking your dose of EVRYSDI through a nasogastric tube, follow the instructions in " D) How to give a dose of EVRYSDI through a nasogastric tube ".

B) How to take a dose of EVRYSDI by mouth

Sit upright when taking a dose of EVRYSDI by mouth.

C) How to give a dose of EVRYSDI through a gastrostomy tube

If you are giving EVRYSDI through a gastrostomy tube, ask your healthcare provider to show you how to inspect the gastrostomy tube before giving EVRYSDI.

D) How to give a dose of EVRYSDI through a nasogastric tube

If you are giving EVRYSDI through a nasogastric tube, ask your healthcare provider to show you how to inspect the nasogastric tube before giving EVRYSDI.

E) How to clean the oral syringe after use

EVRYSDI is a registered trademark of Genentech, Inc.

Distributed by:

Genentech, Inc.

1 DNA Way

South San Francisco, CA 94080-4990

Approved: 2/2025

This Instructions for Use has been Approved by the U.S. Food and Drug Administration.

©2025 Genentech, Inc. All Rights Reserved

EVRYSDI for oral solution and EVRYSDI tablets for oral use contain risdiplam, which is a survival of motor neuron 2 (SMN2)-directed RNA splicing modifier.

The chemical name of risdiplam is 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8 dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido-4H-[1,2-a]pyrimidin-4-one. Risdiplam has a molecular weight of 401.46 g/mol. Risdiplam demonstrates pH-dependent aqueous solubility; the greatest solubility is at low pH, and solubility decreases with increasing pH. Risdiplam has a pKa₁ of 3.78 (base) and pKa₂ of 6.62 (base).

The molecular formula of risdiplam is C₂₂H₂₃N₇O and the chemical structure is shown below.

EVRYSDI for oral solution is supplied as a powder in an amber glass bottle. Each bottle contains 60 mg of risdiplam. The inactive ingredients of EVRYSDI are: ascorbic acid, disodium edetate dihydrate, isomalt, mannitol, polyethylene glycol 6000, sodium benzoate, strawberry flavor, sucralose, and tartaric acid.

The powder is constituted with purified water to yield 60 mg/80 mL (0.75 mg/mL) of risdiplam after constitution [see Dosage and Administration (2.4)].

Each EVRYSDI tablet contains 5 mg of risdiplam. The inactive ingredients of EVRYSDI tablet are colloidal silicon dioxide, crospovidone, mannitol, microcrystalline cellulose, polyethylene glycol 3350, polyvinyl alcohol, sodium stearyl fumarate, strawberry flavor, talc, tartaric acid, titanium dioxide, and yellow iron oxide.

If a dose of EVRYSDI is missed, EVRYSDI should be administered as soon as possible if still within 6 hours of the missed dose, and the usual dosing schedule can be resumed on the next day. Otherwise, the missed dose should be skipped, and the next dose should be taken at the regularly scheduled time on the next day.

If a dose is not fully swallowed or vomiting occurs after taking a dose of EVRYSDI, another dose should not be administered to make up for the lost dose. The patient should wait until the next day to take the next dose at the regularly scheduled time.

The safety and effectiveness of EVRYSDI in pediatric patients (neonates and older) have been established. Use of EVRYSDI for SMA is supported by evidence from adequate and well-controlled studies of EVRYSDI in patients 2 months of age and older with SMA. Use of EVRYSDI for SMA in patients 2 months of age and younger is supported by pharmacokinetic and safety data from pediatric patients 16 days and older, and pharmacokinetic modeling and simulation to identify the dosing regimen [see Clinical Pharmacology (12.3) and Clinical Studies (14)].

Clinical studies of EVRYSDI did not include patients aged 65 years and older to determine whether they respond differently from younger adult patients.

The efficacy of EVRYSDI for the treatment of patients with infantile-onset, later-onset, and pre-symptomatic SMA was evaluated in three clinical studies, Study 1 (NCT02913482) and Study 2 (NCT02908685), and Study 3 (NCT03779334), respectively.

The overall findings of these studies support the effectiveness of EVRYSDI in SMA pediatric and adult patients and appear to support the early initiation of treatment with EVRYSDI.

None.

The most common adverse reactions in later-onset SMA (incidence at least 10% of patients treated with EVRYSDI and more frequent than control) were fever, diarrhea, and rash. (6.1)

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, lower respiratory tract infection, constipation, vomiting, and cough. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Genentech at 1-888-835-2555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Avoid coadministration with drugs that are substrates of multidrug and toxin extrusion (MATE) transporters. (7.1)

Study 2 was a 2-part, multicenter trial to investigate the efficacy, safety, pharmacokinetics, and pharmacodynamics of EVRYSDI for oral solution in patients diagnosed with SMA Type 2 or Type 3. Part 1 of Study 2 was dose-finding and exploratory in 51 patients (14% ambulatory). Part 2 was randomized, double-blind, placebo-controlled, and is described below.

The primary endpoint in Study 2 Part 2 was the change from baseline to Month 12 in the Motor Function Measure 32 (MFM32) score. A key secondary endpoint was the proportion of patients with a 3-point or greater change from baseline to Month 12 in the MFM32 total score. The MFM32 measures motor function abilities that relate to daily functions. The total MFM32 score is expressed as a percentage (range: 0 to 100) of the maximum possible score, with higher scores indicating greater motor function. Another key secondary endpoint was the Revised Upper Limb Module (RULM). The RULM is a tool used to assess motor performance of the upper limb in SMA patients. It tests proximal and distal motor functions of the arm. The total score ranges from 0 (all the items cannot be performed) to 37 (all the activities are achieved fully without any compensatory maneuvers).

Study 2 Part 2 enrolled 180 non-ambulatory patients with Type 2 (71%) or Type 3 (29%) SMA. Patients were randomized 2:1 to receive EVRYSDI at the recommended dosage [see Dosage and Administration (2.1)] or placebo. Randomization was stratified by age group (2 to 5, 6 to 11, 12 to 17, or 18 to 25 years of age).

The median age of patients at the start of treatment was 9.0 years (range: 2 to 25), and the median time between onset of initial SMA symptoms and first treatment was 102.6 months (range: 1 to 275). Of the 180 patients included in the trial, 51% were female, 67% were Caucasian, and 19% were Asian. At baseline, 67% of patients had scoliosis (32% of them with severe scoliosis). Patients had a mean baseline MFM32 score of 46.1, and RULM score of 20.1. Overall baseline demographic characteristics were reasonably balanced between the treatment groups (EVRYSDI and placebo), with the exception of scoliosis (63% in the EVRYSDI arm vs. 73% in the placebo group).

The primary analysis on the change from baseline in MFM32 total score at Month 12 showed a clinically meaningful and statistically significant difference between patients treated with EVRYSDI and placebo. The results of the primary analysis and key secondary endpoints are shown in Table 4 and Figure 1.

EVRYSDI® [ev-RIZ-dee]

(risdiplam)

Tablets, for oral use

Before you start

This Instructions for Use contains information on how to prepare and take EVRYSDI tablets.

Read this Instructions for Use and Patient Information leaflet before you start taking or giving EVRYSDI tablets for the first time and each time you get a refill. There may be new information. This information does not take the place of talking with your healthcare provider about your medical condition or treatment.

If you have any questions about how to take EVRYSDI, contact your healthcare provider.

Important Information

• If you are taking EVRYSDI tablets, the daily dose is one tablet.
• EVRYSDI tablets can be swallowed whole with water. Do not chew, cut, or crush the tablet.
• If you are unable to swallow EVRYSDI tablets whole or have a nasogastric (NG) tube or gastrostomy tube (G-tube), your healthcare provider will show you how to prepare and take EVRYSDI tablets. Always take EVRYSDI tablets exactly as your healthcare provider tells you.
• Do not take or give EVRYSDI tablets until you have been shown the right way to prepare and take or give EVRYSDI.
• Wash your hands before and after preparing, taking or giving EVRYSDI.
• Check the expiration date and check the product for damage before use. Do not use if expired or damaged.
• Avoid getting the EVRYSDI tablet mixture on your skin or in your eyes. If the EVRYSDI tablet mixture gets on your skin, wash the area with soap and water. If the tablet mixture gets in your eyes, rinse your eyes with water.
• Keep the EVRYSDI tablet mixture out of sunlight.
• If you spill the EVRYSDI tablet mixture, dry the area with a dry paper towel and then clean with soap and water. Throw away the paper towel in the trash and wash your hands with soap and water.
• Do not take an extra dose if you vomit at any time after taking EVRYSDI.

Distributed by:

Genentech, USA Inc., A Member of the Roche Group

1 DNA Way, South San Francisco, CA 94080-4990

Evrysdi® is a registered trademark of Genentech, Inc.

©2026 Genentech, Inc.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Approved: 2/2026

In clinical trials for infantile-onset SMA and later-onset SMA patients, EVRYSDI led to an increase in SMN protein with a greater than 2-fold median change from baseline within 4 weeks of treatment initiation across all SMA types studied. The increase was sustained throughout the treatment period (of at least 24 months).

Pharmacokinetics of EVRYSDI have been characterized in healthy adult subjects and in patients with SMA.

After administration of EVRYSDI as an oral solution, pharmacokinetics of risdiplam were approximately linear between 0.6 and 18 mg in a single-ascending-dose study in healthy adult subjects, and between 0.02 and 0.25 mg/kg once daily in a multiple-ascending-dose study in patients with SMA. Following once-daily oral administration of risdiplam in healthy subjects, approximately 3-fold accumulation of peak plasma concentrations (C_max) and area under the plasma concentration-time curve (AUC_0-24h) was observed. Risdiplam exposures reach steady state 7 to 14 days after once daily administration. EVRYSDI tablet (swallowed whole or dispersed in water) demonstrated comparable bioavailability to EVRYSDI for oral solution in adult healthy volunteers under fasted and fed states.

EVRYSDI is administered orally once daily with or without food at approximately the same time each day. The recommended dosage is determined by age and body weight (see Table 1). EVRYSDI tablets are available for patients prescribed the 5 mg dose.

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

Risdiplam is a survival of motor neuron 2 (SMN2) splicing modifier designed to treat patients with spinal muscular atrophy (SMA) caused by mutations in chromosome 5q that lead to SMN protein deficiency. Using in vitro assays and studies in transgenic animal models of SMA, risdiplam was shown to increase exon 7 inclusion in SMN2 messenger ribonucleic acid (mRNA) transcripts and production of full-length SMN protein in the brain.

In vitro and in vivo data indicate that risdiplam may cause alternative splicing of additional genes, including FOXM1 and MADD. FOXM1 and MADD are thought to be involved in cell cycle regulation and apoptosis, respectively, and have been identified as possible contributors to adverse effects seen in animals.

Study 1 was an open-label, 2-part study to investigate the efficacy, safety, pharmacokinetics, and pharmacodynamics of EVRYSDI for oral solution in patients with Type 1 SMA (symptom onset between 28 days and 3 months of age). All patients had genetic confirmation of homozygous deletion or compound heterozygosity predictive of loss of function of the SMN1 gene, and two SMN2 gene copies.

Part 1 of Study 1 was designed as a dose-finding study. Part 2 of Study 1 assessed the safety and efficacy of EVRYSDI at 0.20 mg/kg, the recommended dose determined in Part 1 [see Dosage and Administration (2.4)]. Patients from Part 1 did not take part in Part 2.

A total of 62 patients with symptomatic Type 1 SMA were enrolled in FIREFISH Part 1 (n = 21) and Part 2 (n = 41), of which 58 patients received the recommended dosage [see Dosage and Administration (2.1)]. The median age of onset of clinical signs and symptoms was 1.5 months (range: 0.9 to 3.0 months). The median age at enrollment was 5.6 months (range: 2.2 to 6.9 months), and the median time between onset of symptoms and the first dose was 3.7 months (range 1.0 to 6.0 months). Of these patients, 60% were female, 57% were Caucasian, and 29% were Asian. The demographics and baseline disease characteristics were comparable between Part 1 and Part 2 of the study.

Effectiveness was established based on the ability to sit without support for at least 5 seconds (as measured by Item 22 of the Bayley Scales of Infant and Toddler Development – Third Edition (BSID-III) gross motor scale) and on the basis of survival without permanent ventilation. Permanent ventilation was defined as requiring a tracheostomy or more than 21 consecutive days of either non-invasive ventilation (≥ 16 hours per day) or intubation, in the absence of an acute reversible event.

The primary endpoint was the proportion of patients with the ability to sit without support for at least 5 seconds (BSID-III gross motor scale, Item 22) after 12 months of treatment in Part 2; 29% of patients (n = 12/41) achieved this milestone.

Other efficacy endpoints of EVRYSDI-treated patients in Study 1 (pooled Part 1 and Part 2) are shown in Table 3.

At Month 24, 40% (23/58) of patients who received the recommended dose achieved sitting without support for 30 seconds (BSID-III, Item 26). In addition at Month 24, patients continued to achieve additional motor milestones; 28% (16/58) of patients achieved a standing measure (16% [9/58] supporting weight and 12% [7/58] standing with support), as measured by Section 2 of the Hammersmith Infant Neurological Examination (HINE-2) which assesses motor milestones.

The proportion of patients alive without permanent ventilation (event-free survival) was 84% for all patients at Month 24 (Table 3). Out of 62 patients, 6 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. These results indicate a clinically meaningful deviation from the natural history of untreated infantile-onset SMA. As described in the natural history of untreated infantile-onset SMA, patients would not be expected to attain the ability to sit independently, and no more than 25% of these patients would be expected to survive without permanent ventilation beyond 14 months of age.

Study 3 was an open-label, single-arm, multicenter clinical study to investigate the efficacy, safety, pharmacokinetics, and pharmacodynamics of EVRYSDI in infants up to 6 weeks of age (at first dose) who have been genetically diagnosed with SMA but do not yet present with symptoms.

The efficacy in pre-symptomatic SMA patients was evaluated at Month 12 in 26 patients treated with EVRYSDI in Study 3: 8 patients had 2 copies of the SMN2 gene, 13 patients had 3 copies, and 5 patients had 4 or more copies. The median age of these patients at first dose was 25 days (range: 16 to 41), 62% were female, and 85% were Caucasian. The primary efficacy population (N = 5) included patients with 2 SMN2 copies and a baseline CMAP amplitude ≥1.5 mV.

The primary efficacy endpoint was the proportion of patients with the ability to sit without support for at least 5 seconds (BSID-III gross motor scale, Item 22) at Month 12. This milestone was achieved by 80% (4/5) of patients in the primary efficacy population. This milestone was also achieved by 87.5% (7/8) of all patients with 2 copies of SMN2 and 96.2% (25/26) of patients in the full treated population.

At Month 12, 80.8% (21/26) of patients in the full treated population achieved sitting without support for 30 seconds (BSID-III, Item 26). Of the 26 patients treated with EVRYSDI, 25 patients had motor milestones measured by the HINE-2 at Month 12. Of these, 24 (96%) achieved sitting (23 patients could pivot/rotate and 1 achieved stable sit); 21 (84%) could stand (13 patients could stand unaided and 8 could stand with support); and 12 (48%) could walk independently. Seven patients were not tested for walking at Month 12. All 26 patients were alive at 12 months without permanent ventilation.

• Administer once daily with or without food per the table below (2.1):

• Swallow EVRYSDI tablet whole with water or dispersed in non-chlorinated drinking water (e.g., filtered water). (2.2)
• Administer EVRYSDI for oral solution with the provided oral syringe. (2.2)
• EVRYSDI for oral solution must be constituted by a healthcare provider prior to dispensing. (2.4)
• See Full Prescribing Information for important preparation and administration instructions. (2.2, 2.4)

EVRYSDI for oral solution: 60 mg as a light yellow, pale yellow, yellow, greyish yellow, greenish yellow, or light green powder for constitution. Following constitution, the volume of the greenish yellow to yellow solution is 80 mL, providing 60 mg/80 mL (0.75 mg/mL) risdiplam.

EVRYSDI tablet: 5 mg as a pale yellow film-coated tablet, round and curved, with EVR debossed on one side.

Pregnancy: Based on animal data, may cause fetal harm. (8.1)

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in practice.

In clinical trials including patients with infantile-onset SMA, later-onset SMA, and pre-symptomatic SMA, a total of 491 patients (51% female, 74% Caucasian) were exposed to EVRYSDI for up to a median duration of 48.1 months (range: 0.6 to 63.4 months), with 231 patients receiving treatment for more than 24 months. At the time of first EVRYSDI dose, 90 (18%) patients were 18 years and older, 119 (24%) were 12 years to less than 18 years, 189 (39%) were 2 years to less than 12 years, 67 (14%) 2 months to less than 2 years, and 26 (5%) were less than 2 months.

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).

It is recommended that a healthcare provider discuss with the patient or caregiver how to prepare the prescribed daily dose prior to administration of the first dose [see Instructions for Use for EVRYSDI for Oral Solution and EVRYSDI Tablets and Patient Information].

Studies of risdiplam in juvenile and adult rats and in monkeys demonstrated adverse effects on the reproductive organs, including germ cells, in males at clinically relevant plasma exposures [see Use in Specific Populations (8.4) and Nonclinical Toxicology (13.1)].

NDC 50242-202-01

Evrysdi^®

(risdiplam)

Tablets

5 mg

Do not chew, cut,

or crush tablet.

30 Tablets

Rx only

Genentech

11044980

NDC 50242-175-07

Evrysdi^®

(risdiplam)

for oral solution

60 mg/80 mL

(0.75 mg/mL)

Attention pharmacist: Evrysdi must be

constituted with water prior to dispensing.

80 mL (2.71 fl oz) total volume after constitution

Rx only

Genentech

11044976

EVRYSDI powder must be constituted to the oral solution by a pharmacist or other healthcare provider prior to dispensing to the patient.

Based on in vitro data, EVRYSDI may increase plasma concentrations of drugs eliminated via MATE1 or MATE2-K [see Clinical Pharmacology (12.3)], such as metformin. Avoid coadministration of EVRYSDI with MATE substrates. If coadministration cannot be avoided, monitor for drug-related toxicities and consider dosage reduction of the coadministered drug (based on the labeling of that drug) if needed.

EVRYSDI for Oral Solution

In infants who are breastfed, EVRYSDI for oral solution can be administered before or after breastfeeding. EVRYSDI cannot be mixed with formula or milk.

Instruct patients or caregivers to administer the dose using the reusable oral syringe provided.

EVRYSDI for oral solution must be taken immediately after it is drawn up into the oral syringe. If EVRYSDI is not taken within 5 minutes, EVRYSDI should be discarded from the oral syringe, and a new dose should be prepared.

Instruct patients to drink water after taking EVRYSDI for oral solution to ensure the drug has been completely swallowed.

EVRYSDI for oral solution can be administered via a nasogastric or gastrostomy tube. The tube should be flushed with water after delivering EVRYSDI for oral solution [see Instructions for Use].

Storage and Handling

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Keep in the original bottle. Keep the bottle tightly closed in order to protect from moisture.

INSTRUCTIONS FOR USE

EVRYSDI^® [ev-RIZ-dee]

(risdiplam)

for oral solution

Please read and understand this Instructions for Use and the Patient Information leaflet before you start taking EVRYSDI for information about EVRYSDI and how to prepare and give EVRYSDI through an oral syringe, gastrostomy tube (G-tube), or nasogastric tube (NG-tube).

If you have any questions about how to take EVRYSDI, contact your healthcare provider.

EVRYSDI should come as a liquid in a bottle when you receive it from the pharmacy. Do not take EVRYSDI and contact your pharmacist if the medicine in the bottle is a powder.

Each EVRYSDI carton contains (see Figure A):

Important information about EVRYSDI

• Ask your healthcare provider to show you the correct oral syringe you should use and how to measure your prescribed daily dose.
• Always use the reusable oral syringes that come with EVRYSDI to measure your prescribed daily dose. If your carton does not contain two identical syringes, contact your pharmacist.
• Always take EVRYSDI exactly as your healthcare provider tells you to take it.
• Take EVRYSDI 1 time daily with or without a meal at approximately the same time each day.
• Do not take EVRYSDI if the bottle adapter is not in the bottle. If the bottle adapter is not in the bottle, contact your pharmacist.
• Do not mix EVRYSDI into food or liquids. Do not mix EVRYSDI with formula or milk.
• Do not take EVRYSDI if the bottle or oral syringes are damaged.
• Avoid getting EVRYSDI on your skin or in your eyes. If EVRYSDI gets on your skin, wash the area with soap and water. If EVRYSDI gets in your eyes, rinse your eyes with water.
• If you spill EVRYSDI, dry the area with a dry paper towel and then clean with water. Throw away the paper towel in the trash and wash your hands well with soap and water.
• If there is not enough EVRYSDI left in the bottle for your prescribed dose, throw away (discard) the bottle with remaining EVRYSDI and used oral syringes according to your local requirements.
• Use a new bottle of EVRYSDI to get your prescribed dose.
  
  Do not mix EVRYSDI from the new bottle with the bottle you are currently using.

How to store EVRYSDI

A) Preparing and withdrawing your dose

How to prepare your dose of EVRYSDI

If you are taking your dose of EVRYSDI by mouth, follow the instructions in " B) How to take a dose of EVRYSDI by mouth ".

If you are taking your dose of EVRYSDI through a gastrostomy tube, follow the instructions in " C) How to give a dose of EVRYSDI through a gastrostomy tube ".

If you are taking your dose of EVRYSDI through a nasogastric tube, follow the instructions in " D) How to give a dose of EVRYSDI through a nasogastric tube ".

B) How to take a dose of EVRYSDI by mouth

Sit upright when taking a dose of EVRYSDI by mouth.

C) How to give a dose of EVRYSDI through a gastrostomy tube

If you are giving EVRYSDI through a gastrostomy tube, ask your healthcare provider to show you how to inspect the gastrostomy tube before giving EVRYSDI.

D) How to give a dose of EVRYSDI through a nasogastric tube

If you are giving EVRYSDI through a nasogastric tube, ask your healthcare provider to show you how to inspect the nasogastric tube before giving EVRYSDI.

E) How to clean the oral syringe after use

EVRYSDI is a registered trademark of Genentech, Inc.

Distributed by:

Genentech, Inc.

1 DNA Way

South San Francisco, CA 94080-4990

Approved: 2/2025

This Instructions for Use has been Approved by the U.S. Food and Drug Administration.

©2025 Genentech, Inc. All Rights Reserved

EVRYSDI for oral solution and EVRYSDI tablets for oral use contain risdiplam, which is a survival of motor neuron 2 (SMN2)-directed RNA splicing modifier.

The chemical name of risdiplam is 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8 dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido-4H-[1,2-a]pyrimidin-4-one. Risdiplam has a molecular weight of 401.46 g/mol. Risdiplam demonstrates pH-dependent aqueous solubility; the greatest solubility is at low pH, and solubility decreases with increasing pH. Risdiplam has a pKa₁ of 3.78 (base) and pKa₂ of 6.62 (base).

The molecular formula of risdiplam is C₂₂H₂₃N₇O and the chemical structure is shown below.

EVRYSDI for oral solution is supplied as a powder in an amber glass bottle. Each bottle contains 60 mg of risdiplam. The inactive ingredients of EVRYSDI are: ascorbic acid, disodium edetate dihydrate, isomalt, mannitol, polyethylene glycol 6000, sodium benzoate, strawberry flavor, sucralose, and tartaric acid.

The powder is constituted with purified water to yield 60 mg/80 mL (0.75 mg/mL) of risdiplam after constitution [see Dosage and Administration (2.4)].

Each EVRYSDI tablet contains 5 mg of risdiplam. The inactive ingredients of EVRYSDI tablet are colloidal silicon dioxide, crospovidone, mannitol, microcrystalline cellulose, polyethylene glycol 3350, polyvinyl alcohol, sodium stearyl fumarate, strawberry flavor, talc, tartaric acid, titanium dioxide, and yellow iron oxide.

If a dose of EVRYSDI is missed, EVRYSDI should be administered as soon as possible if still within 6 hours of the missed dose, and the usual dosing schedule can be resumed on the next day. Otherwise, the missed dose should be skipped, and the next dose should be taken at the regularly scheduled time on the next day.

If a dose is not fully swallowed or vomiting occurs after taking a dose of EVRYSDI, another dose should not be administered to make up for the lost dose. The patient should wait until the next day to take the next dose at the regularly scheduled time.

The safety and effectiveness of EVRYSDI in pediatric patients (neonates and older) have been established. Use of EVRYSDI for SMA is supported by evidence from adequate and well-controlled studies of EVRYSDI in patients 2 months of age and older with SMA. Use of EVRYSDI for SMA in patients 2 months of age and younger is supported by pharmacokinetic and safety data from pediatric patients 16 days and older, and pharmacokinetic modeling and simulation to identify the dosing regimen [see Clinical Pharmacology (12.3) and Clinical Studies (14)].

Clinical studies of EVRYSDI did not include patients aged 65 years and older to determine whether they respond differently from younger adult patients.

The efficacy of EVRYSDI for the treatment of patients with infantile-onset, later-onset, and pre-symptomatic SMA was evaluated in three clinical studies, Study 1 (NCT02913482) and Study 2 (NCT02908685), and Study 3 (NCT03779334), respectively.

The overall findings of these studies support the effectiveness of EVRYSDI in SMA pediatric and adult patients and appear to support the early initiation of treatment with EVRYSDI.

None.

The most common adverse reactions in later-onset SMA (incidence at least 10% of patients treated with EVRYSDI and more frequent than control) were fever, diarrhea, and rash. (6.1)

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, lower respiratory tract infection, constipation, vomiting, and cough. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Genentech at 1-888-835-2555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Avoid coadministration with drugs that are substrates of multidrug and toxin extrusion (MATE) transporters. (7.1)

Study 2 was a 2-part, multicenter trial to investigate the efficacy, safety, pharmacokinetics, and pharmacodynamics of EVRYSDI for oral solution in patients diagnosed with SMA Type 2 or Type 3. Part 1 of Study 2 was dose-finding and exploratory in 51 patients (14% ambulatory). Part 2 was randomized, double-blind, placebo-controlled, and is described below.

The primary endpoint in Study 2 Part 2 was the change from baseline to Month 12 in the Motor Function Measure 32 (MFM32) score. A key secondary endpoint was the proportion of patients with a 3-point or greater change from baseline to Month 12 in the MFM32 total score. The MFM32 measures motor function abilities that relate to daily functions. The total MFM32 score is expressed as a percentage (range: 0 to 100) of the maximum possible score, with higher scores indicating greater motor function. Another key secondary endpoint was the Revised Upper Limb Module (RULM). The RULM is a tool used to assess motor performance of the upper limb in SMA patients. It tests proximal and distal motor functions of the arm. The total score ranges from 0 (all the items cannot be performed) to 37 (all the activities are achieved fully without any compensatory maneuvers).

Study 2 Part 2 enrolled 180 non-ambulatory patients with Type 2 (71%) or Type 3 (29%) SMA. Patients were randomized 2:1 to receive EVRYSDI at the recommended dosage [see Dosage and Administration (2.1)] or placebo. Randomization was stratified by age group (2 to 5, 6 to 11, 12 to 17, or 18 to 25 years of age).

The median age of patients at the start of treatment was 9.0 years (range: 2 to 25), and the median time between onset of initial SMA symptoms and first treatment was 102.6 months (range: 1 to 275). Of the 180 patients included in the trial, 51% were female, 67% were Caucasian, and 19% were Asian. At baseline, 67% of patients had scoliosis (32% of them with severe scoliosis). Patients had a mean baseline MFM32 score of 46.1, and RULM score of 20.1. Overall baseline demographic characteristics were reasonably balanced between the treatment groups (EVRYSDI and placebo), with the exception of scoliosis (63% in the EVRYSDI arm vs. 73% in the placebo group).

The primary analysis on the change from baseline in MFM32 total score at Month 12 showed a clinically meaningful and statistically significant difference between patients treated with EVRYSDI and placebo. The results of the primary analysis and key secondary endpoints are shown in Table 4 and Figure 1.

EVRYSDI® [ev-RIZ-dee]

(risdiplam)

Tablets, for oral use

Before you start

This Instructions for Use contains information on how to prepare and take EVRYSDI tablets.

Read this Instructions for Use and Patient Information leaflet before you start taking or giving EVRYSDI tablets for the first time and each time you get a refill. There may be new information. This information does not take the place of talking with your healthcare provider about your medical condition or treatment.

If you have any questions about how to take EVRYSDI, contact your healthcare provider.

Important Information

• If you are taking EVRYSDI tablets, the daily dose is one tablet.
• EVRYSDI tablets can be swallowed whole with water. Do not chew, cut, or crush the tablet.
• If you are unable to swallow EVRYSDI tablets whole or have a nasogastric (NG) tube or gastrostomy tube (G-tube), your healthcare provider will show you how to prepare and take EVRYSDI tablets. Always take EVRYSDI tablets exactly as your healthcare provider tells you.
• Do not take or give EVRYSDI tablets until you have been shown the right way to prepare and take or give EVRYSDI.
• Wash your hands before and after preparing, taking or giving EVRYSDI.
• Check the expiration date and check the product for damage before use. Do not use if expired or damaged.
• Avoid getting the EVRYSDI tablet mixture on your skin or in your eyes. If the EVRYSDI tablet mixture gets on your skin, wash the area with soap and water. If the tablet mixture gets in your eyes, rinse your eyes with water.
• Keep the EVRYSDI tablet mixture out of sunlight.
• If you spill the EVRYSDI tablet mixture, dry the area with a dry paper towel and then clean with soap and water. Throw away the paper towel in the trash and wash your hands with soap and water.
• Do not take an extra dose if you vomit at any time after taking EVRYSDI.

Distributed by:

Genentech, USA Inc., A Member of the Roche Group

1 DNA Way, South San Francisco, CA 94080-4990

Evrysdi® is a registered trademark of Genentech, Inc.

©2026 Genentech, Inc.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Approved: 2/2026

In clinical trials for infantile-onset SMA and later-onset SMA patients, EVRYSDI led to an increase in SMN protein with a greater than 2-fold median change from baseline within 4 weeks of treatment initiation across all SMA types studied. The increase was sustained throughout the treatment period (of at least 24 months).

Pharmacokinetics of EVRYSDI have been characterized in healthy adult subjects and in patients with SMA.

After administration of EVRYSDI as an oral solution, pharmacokinetics of risdiplam were approximately linear between 0.6 and 18 mg in a single-ascending-dose study in healthy adult subjects, and between 0.02 and 0.25 mg/kg once daily in a multiple-ascending-dose study in patients with SMA. Following once-daily oral administration of risdiplam in healthy subjects, approximately 3-fold accumulation of peak plasma concentrations (C_max) and area under the plasma concentration-time curve (AUC_0-24h) was observed. Risdiplam exposures reach steady state 7 to 14 days after once daily administration. EVRYSDI tablet (swallowed whole or dispersed in water) demonstrated comparable bioavailability to EVRYSDI for oral solution in adult healthy volunteers under fasted and fed states.

EVRYSDI is administered orally once daily with or without food at approximately the same time each day. The recommended dosage is determined by age and body weight (see Table 1). EVRYSDI tablets are available for patients prescribed the 5 mg dose.

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

Risdiplam is a survival of motor neuron 2 (SMN2) splicing modifier designed to treat patients with spinal muscular atrophy (SMA) caused by mutations in chromosome 5q that lead to SMN protein deficiency. Using in vitro assays and studies in transgenic animal models of SMA, risdiplam was shown to increase exon 7 inclusion in SMN2 messenger ribonucleic acid (mRNA) transcripts and production of full-length SMN protein in the brain.

In vitro and in vivo data indicate that risdiplam may cause alternative splicing of additional genes, including FOXM1 and MADD. FOXM1 and MADD are thought to be involved in cell cycle regulation and apoptosis, respectively, and have been identified as possible contributors to adverse effects seen in animals.

Study 1 was an open-label, 2-part study to investigate the efficacy, safety, pharmacokinetics, and pharmacodynamics of EVRYSDI for oral solution in patients with Type 1 SMA (symptom onset between 28 days and 3 months of age). All patients had genetic confirmation of homozygous deletion or compound heterozygosity predictive of loss of function of the SMN1 gene, and two SMN2 gene copies.

Part 1 of Study 1 was designed as a dose-finding study. Part 2 of Study 1 assessed the safety and efficacy of EVRYSDI at 0.20 mg/kg, the recommended dose determined in Part 1 [see Dosage and Administration (2.4)]. Patients from Part 1 did not take part in Part 2.

A total of 62 patients with symptomatic Type 1 SMA were enrolled in FIREFISH Part 1 (n = 21) and Part 2 (n = 41), of which 58 patients received the recommended dosage [see Dosage and Administration (2.1)]. The median age of onset of clinical signs and symptoms was 1.5 months (range: 0.9 to 3.0 months). The median age at enrollment was 5.6 months (range: 2.2 to 6.9 months), and the median time between onset of symptoms and the first dose was 3.7 months (range 1.0 to 6.0 months). Of these patients, 60% were female, 57% were Caucasian, and 29% were Asian. The demographics and baseline disease characteristics were comparable between Part 1 and Part 2 of the study.

Effectiveness was established based on the ability to sit without support for at least 5 seconds (as measured by Item 22 of the Bayley Scales of Infant and Toddler Development – Third Edition (BSID-III) gross motor scale) and on the basis of survival without permanent ventilation. Permanent ventilation was defined as requiring a tracheostomy or more than 21 consecutive days of either non-invasive ventilation (≥ 16 hours per day) or intubation, in the absence of an acute reversible event.

The primary endpoint was the proportion of patients with the ability to sit without support for at least 5 seconds (BSID-III gross motor scale, Item 22) after 12 months of treatment in Part 2; 29% of patients (n = 12/41) achieved this milestone.

Other efficacy endpoints of EVRYSDI-treated patients in Study 1 (pooled Part 1 and Part 2) are shown in Table 3.

At Month 24, 40% (23/58) of patients who received the recommended dose achieved sitting without support for 30 seconds (BSID-III, Item 26). In addition at Month 24, patients continued to achieve additional motor milestones; 28% (16/58) of patients achieved a standing measure (16% [9/58] supporting weight and 12% [7/58] standing with support), as measured by Section 2 of the Hammersmith Infant Neurological Examination (HINE-2) which assesses motor milestones.

The proportion of patients alive without permanent ventilation (event-free survival) was 84% for all patients at Month 24 (Table 3). Out of 62 patients, 6 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. These results indicate a clinically meaningful deviation from the natural history of untreated infantile-onset SMA. As described in the natural history of untreated infantile-onset SMA, patients would not be expected to attain the ability to sit independently, and no more than 25% of these patients would be expected to survive without permanent ventilation beyond 14 months of age.

Study 3 was an open-label, single-arm, multicenter clinical study to investigate the efficacy, safety, pharmacokinetics, and pharmacodynamics of EVRYSDI in infants up to 6 weeks of age (at first dose) who have been genetically diagnosed with SMA but do not yet present with symptoms.

The efficacy in pre-symptomatic SMA patients was evaluated at Month 12 in 26 patients treated with EVRYSDI in Study 3: 8 patients had 2 copies of the SMN2 gene, 13 patients had 3 copies, and 5 patients had 4 or more copies. The median age of these patients at first dose was 25 days (range: 16 to 41), 62% were female, and 85% were Caucasian. The primary efficacy population (N = 5) included patients with 2 SMN2 copies and a baseline CMAP amplitude ≥1.5 mV.

The primary efficacy endpoint was the proportion of patients with the ability to sit without support for at least 5 seconds (BSID-III gross motor scale, Item 22) at Month 12. This milestone was achieved by 80% (4/5) of patients in the primary efficacy population. This milestone was also achieved by 87.5% (7/8) of all patients with 2 copies of SMN2 and 96.2% (25/26) of patients in the full treated population.

At Month 12, 80.8% (21/26) of patients in the full treated population achieved sitting without support for 30 seconds (BSID-III, Item 26). Of the 26 patients treated with EVRYSDI, 25 patients had motor milestones measured by the HINE-2 at Month 12. Of these, 24 (96%) achieved sitting (23 patients could pivot/rotate and 1 achieved stable sit); 21 (84%) could stand (13 patients could stand unaided and 8 could stand with support); and 12 (48%) could walk independently. Seven patients were not tested for walking at Month 12. All 26 patients were alive at 12 months without permanent ventilation.

• Administer once daily with or without food per the table below (2.1):

• Swallow EVRYSDI tablet whole with water or dispersed in non-chlorinated drinking water (e.g., filtered water). (2.2)
• Administer EVRYSDI for oral solution with the provided oral syringe. (2.2)
• EVRYSDI for oral solution must be constituted by a healthcare provider prior to dispensing. (2.4)
• See Full Prescribing Information for important preparation and administration instructions. (2.2, 2.4)

EVRYSDI for oral solution: 60 mg as a light yellow, pale yellow, yellow, greyish yellow, greenish yellow, or light green powder for constitution. Following constitution, the volume of the greenish yellow to yellow solution is 80 mL, providing 60 mg/80 mL (0.75 mg/mL) risdiplam.

EVRYSDI tablet: 5 mg as a pale yellow film-coated tablet, round and curved, with EVR debossed on one side.

Pregnancy: Based on animal data, may cause fetal harm. (8.1)

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in practice.

In clinical trials including patients with infantile-onset SMA, later-onset SMA, and pre-symptomatic SMA, a total of 491 patients (51% female, 74% Caucasian) were exposed to EVRYSDI for up to a median duration of 48.1 months (range: 0.6 to 63.4 months), with 231 patients receiving treatment for more than 24 months. At the time of first EVRYSDI dose, 90 (18%) patients were 18 years and older, 119 (24%) were 12 years to less than 18 years, 189 (39%) were 2 years to less than 12 years, 67 (14%) 2 months to less than 2 years, and 26 (5%) were less than 2 months.

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).

It is recommended that a healthcare provider discuss with the patient or caregiver how to prepare the prescribed daily dose prior to administration of the first dose [see Instructions for Use for EVRYSDI for Oral Solution and EVRYSDI Tablets and Patient Information].

Studies of risdiplam in juvenile and adult rats and in monkeys demonstrated adverse effects on the reproductive organs, including germ cells, in males at clinically relevant plasma exposures [see Use in Specific Populations (8.4) and Nonclinical Toxicology (13.1)].

NDC 50242-202-01

Evrysdi^®

(risdiplam)

Tablets

5 mg

Do not chew, cut,

or crush tablet.

30 Tablets

Rx only

Genentech

11044980

NDC 50242-175-07

Evrysdi^®

(risdiplam)

for oral solution

60 mg/80 mL

(0.75 mg/mL)

Attention pharmacist: Evrysdi must be

constituted with water prior to dispensing.

80 mL (2.71 fl oz) total volume after constitution

Rx only

Genentech

11044976

EVRYSDI powder must be constituted to the oral solution by a pharmacist or other healthcare provider prior to dispensing to the patient.

Based on in vitro data, EVRYSDI may increase plasma concentrations of drugs eliminated via MATE1 or MATE2-K [see Clinical Pharmacology (12.3)], such as metformin. Avoid coadministration of EVRYSDI with MATE substrates. If coadministration cannot be avoided, monitor for drug-related toxicities and consider dosage reduction of the coadministered drug (based on the labeling of that drug) if needed.