For Patients and Caregivers

Results in later-onset SMA: adults and children

Results in later-onset SMA: adults and children

Evrysdi®️ (risdiplam) children and adults living with SMA

Adults and children 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 231 patients 2 to 25 years of age with later-onset (Type 2 or 3) 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

Helping preserve daily function1

Significantly improved or preserved motor skills vs placebo at 12 months, 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)
  • The MFM-32 is a 32-item scale designed to assess various motor functions in people with neuromuscular disorders. The scale measures motor function abilities that relate to important daily functions19,20
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. The MFM-32 total score is calculated as a percentage of the maximum score of 96.

*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.

EXPLORATORY ASSESSMENTS SUGGEST

Improvement in upper limb function at 12 months was maintained for 48 months16

SUNFISH PART 2

Change in MFM-32 score over 48 months of treatment

0.84-point mean change from baseline with Evrysdi at 48 months (95% CI: -0.51, 2.19).
These 48-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 36 months. Evrysdi period not shown. After 24 months, participants had the opportunity to enter the open-label extension portion of the study.
†Number of patients with an available total score (result) at respective time points. Intent-to-treat patients.
MFM-32=Motor Function Measure–32 Items; NA=not applicable.

Meaningful improvement in upper limb function1

Greater strength in hand and arm movements important for activities of everyday life vs placebo at 12 months, as measured by RULM1

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
These results demonstrated a clinically meaningful difference for patients treated with Evrysdi compared with placebo1

*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).

EXPLORATORY ASSESSMENTS SUGGEST

Improvement in upper limb function at 12 months was maintained for 48 months16

SUNFISH PART 2

Change in RULM score over 48 months of treatment

2.58-point mean change from baseline with Evrysdi at 48 months (95% CI: 1.62, 3.55).
These 48-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 36 months. Evrysdi period not shown. After 24 months, participants had the opportunity to enter the open-label extension portion of the study.

†Number of patients with an available total score (result) at respective time points. Intent-to-treat patients.

NA=not applicable; RULM=Revised Upper Limb Module.

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

Hear perspectives from peers

Dr. Shadé Moody and Angela discuss treatment considerations

Angela, an adult who lives with Type 2 SMA shares her treatment experience. Neurologist Dr. Shadé Moody sheds light on the same considerations from her perspective.

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Angela
Hi. My name is Angela. I live here in Houston, Texas, with my wonderful husband, Justin. I have SMA Type 2. I was diagnosed at 16 months old way back in the late seventies. And we have a wonderful life here in Houston.

So growing up I was able to crawl, and I could pull up on furniture, but when I let go, I wasn’t able to bear weight. And then slowly, with the SMA progression, I slowly got a little bit weaker, and I used a manual wheelchair, and I could push myself a little bit and then starting in middle school, I really lost a lot of my arm strength and went into a power chair and yet I could still do those important things to me. So I’ve always been able to feed myself. I got into makeup when I was pretty little. So starting in about sixth grade, I had my blue eyeshadow that I was able to do myself and can continue to do that as well now that I'm in my forties.

You know, having SMA certainly has brought a lifetime of limitations that I’ve had to figure out how to navigate through that. And being a teacher, as my career, is one of those solutions because I have 23 amazing little people that are able to help me with the physical task of the job that I can’t do. So, turning on the light switches, opening marker caps, even to the point of at the end of the day when my arms are exhausted and one of my students will come and lift my arm up and put it so that I can drive my chair again. Like that’s a beautiful thing for me to get to see every day.

I’ve always been a person who just has a really independent spirit. And whether it means I’m going to be able to do something myself, or if I’m going to help to put the right people in place to help me accomplish that task, I’m just going to figure it out.

Dr. Moody
The older patients I care for are in their late teens and early to mid-20s, and all of them are nonambulatory. In my experience, older patients with SMA, like Angela, live full lives within the limitations of their diagnosis. They’ve learned to live with their physical limitations, but they strive to achieve their greatest potential. They’re interested in their relationships, and they want to be involved in the community. 

I stress that SMA is progressive, and that, without treatment, natural history data suggests that their disease will progress. They may not realize those changes from day to day, but they are happening. I have lengthy discussions with my SMA patients stressing that we need to do something to slow the disease progression or stabilize the course of the disease. For some patients, that progression can be devastating.

Angela
My progression has been slow and isn’t obvious from day to day. When thinking back, I realize how my disease has progressed. For example, when I was first teaching, I could use an overhead projector, and now, I can no longer do that.

SMA is like a string of lights. As one bulb goes out, you don’t really notice. But over time, when more and more bulbs go out, all of a sudden, you’re in the dark.

Dr. Moody
I like to ask my patients what their life looks like now so I can understand what type of things are important to them. Then my goal becomes helping them to maintain that level of function. For nonambulatory patients, that might mean maintaining the upper limb function that they have at baseline so they can continue to text, or write, or feed themselves, or put on their makeup. If we are lucky, there may be some improvement, but my goal is to maintain motor function. I want to build trust with my patients and their families, and to do that, it’s important to set reasonable expectations before we begin therapy. I tell them that, in my opinion, if they maintain the function they have and if they’re satisfied with their overall experience with their therapy, the drug is a good fit for them. Anything else would be an added benefit.

Angela
I definitely wanted just to maintain where my current motor function is. I wanted to be able to continue to do all of those life daily activities that are important to me. I thought about how important my arm and hand function were to my daily living. It allowed me to brush my teeth and put on my own makeup. That’s really important to me, because it’s less caregiver time. I didn’t want to get to a point where I needed to bring in more help, or where my husband needed to assist me, because we’ve built a life around the things that I’m able to do, and I wanted to maintain as much motor function as I can, so that I could keep doing the things that are important to me.

So I had heard on social media that there was a medication coming out that was an oral medication, that happened to be Evrysdi. My neurologist had a great conversation with me about Evrysdi. We talked about the potential side effects that could take place, but also the things that could possibly happen after taking it. And so we decided that was a good choice for me.

SMA has not given me a lot of choices over the years; whatever it said, I had to go along with. I have an opportunity to make a choice, and that for me is to seek treatment and to try and slow the progression of a disease that is going to continue.

Dr. Moody
Patients may hesitate to begin treatment because of fear about medication-related side effects or the burden of treatment. I make sure to address these concerns up front, and together, we weigh potential drawbacks associated with treatments against disease progression. I review potential adverse reactions with the patients before prescribing Evrysdi.

For young women, I review potential information around pregnancy and potential risks to the fetus. We talk about contraception, and I counsel them to let me know if they’re considering starting a family so we can plan to stop treatment before they become pregnant.

Young men or parents of younger males are interested in learning about possible effects on male fertility. I take time to review that and discuss options such as sperm preservation. I refer them to a fertility specialist if they’re interested.

Angela
When I first started taking Evrysdi, I had a little bit of an upset tummy. And so I talked to my neurologist, and she said, "Try adding a little bit more food when you eat breakfast." And so I did, and I know everyone’s different, but for me it worked, and I didn’t experience that anymore.

Dr Moody
I tell patients that GI side effects are common with Evrysdi, and I caution them to take Evrysdi after a full meal. I tell patients to let us know if GI side effects, such as diarrhea, are occurring, and I'll help them to work through them. Some of these issues may be related to Evrysdi while some may be related to SMA itself. We talk about other potential adverse events as well.

With all of my patients, I review all medications they’re taking before starting Evrysdi, including vitamins and over-the-counter supplements. For instance, if I have a patient who typically takes a laxative, we talk about whether we should adjust that. We review how and when to take Evrysdi, for example, after a meal then followed by water, and we make a plan to connect immediately if they do experience any side effects so we can determine the best way to address them together.

I look at functional motor skills when evaluating treatment. For example, if a patient was able to lift a glass at baseline, I want to see if they can still lift the glass. I do motor function skills to quantify changes in motor function, but activities of daily living mean more to the patient than the numbers on the scale results.

I also look at their SMA as a whole. I ask about respiratory function. I may ask about illnesses or hospitalizations. That’s part of the comprehensive care of the SMA patient. Sometimes patients get discouraged if they don’t see improvement, and I remind them of the progressive nature of SMA and to think about what motor function decline can mean for them. I remind them that the goal is to maintain motor function.

Angela
I realize everyone has a different experience, but for me, Evrysdi has made a difference. I don’t notice any specific changes in my motor function from day-to-day, but the last time I went to the neurologist, they noticed improvement on my RULM test. I was able to tear the paper, which is something that I couldn’t do before, and we celebrated. I was still able to move the jar of coins from one circle to the other.

Taking Evrysdi at home fits with my lifestyle, and it fits with my schedule.

I would want all neurologists that are treating people with SMA to have the same relationship that I have with my neurologist. And that is, you know, she knows what my daily life looks like. She knows what my goals, what my purpose is in life. We have that kind of relationship, and she knew that with me taking Evrysdi it meant that I could continue to fight the progression of a disease that could potentially take some of those things away from me.

Dr. Moody
It’s an exciting time, and options are available, and all patients with SMA should be treated. You should discuss treatment with your adult patients at their annual visits and encourage them to learn about disease-modifying therapies. Take advantage of the multidisciplinary care available for SMA.

Angela

In talking to other people about Evrysdi, I love telling them that Evrysdi for me is about taking action, and I get to take action every single day by taking Evrysdi.

Dr. Perry Shieh and Shaniqua explore expectation setting

Shaniqua, an adult living with Type 3 SMA, conveys her experiences with Evrysdi. Dr. Perry Shieh shares his related insights on discussing expectation setting and Evrysdi.

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Shaniqua
My name is Shaniqua. I am attorney living in Silver Spring, Maryland, and I have spinal muscular atrophy type 3, also known as SMA. I was diagnosed with SMA around the age of two and a half. My mother noticed that I was falling a lot. I wasn't able to climb on the monkey bars. I use my wheelchair normally when I'm working, I'm at my desk, but sometimes I do get up and I walk around. I walk to like the sink to start cooking. Now, though I do use a cane, but sometimes I could just move around without the cane. 

I have a great support system, including my mom and my grandma, my dad, and a whole host of cousins. They really support me with my SMA, and they assist in anything I need help with.

Dr. Shieh
Most of my older patients have Type 2 SMA and many of my Type 3 SMA patients are no longer ambulatory. My oldest patients are in their early sixties, but most of my patients are in their teens. 

Although some patients are still able to stand or walk, most of my patients are wheelchair bound. Despite these physical limitations, I find that, like Shaniqua, people living with SMA are resilient. They pursue their goals, despite their disabilities. They may be wheelchair bound, but they accommodate so that they can do the things that they want to do. Overall, this is a very inspiring group of patients.

Some people living with SMA don't realize that their motor function is declining. I have heard ambulatory patients say, "I can still walk. I don't think I'm progressing." So, when disease-modifying therapies first became available, some of these patients did not feel a sense of urgency to seek these treatments. However, I am honest with my patients. I tell my patients with SMA that they will continue to lose motor function over time. If they don't start on a disease-modifying therapy, they run a greater risk of losing motor function.

Shaniqua
I noticed over the years that I was slowly losing some of my motor functions. I was falling a lot. I was unable to walk up and down the stairs. I was unable to walk long distances. I had to use a cane to walk or I had to use a motorized scooter to walk. I noticed that it was becoming harder to like open bottles. It was becoming harder to put my hair up like in a ponytail.

When I was younger, I saw my neurologist once a year, but there was not much we can do, but manage my symptoms.

My goal is to continue and maintain some of the things that I'm able to do on my own, such as bathing, showering, brushing my teeth, doing my hair, cooking, working. Maintaining my health is important to me. Being able to live alone is important to me. Spending time with my family and friends is important to me.

Dr. Shieh
My goal is to get the patient started on a disease-modifying therapy to maintain whatever motor function the patient still has. So I set expectations about goals before therapy starts. I reinforce that disease-modifying therapy can't bring back motor neurons that they have already lost. I tell patients that they may not see improvement in motor function. However, in later onset SMA the goal is really to stabilize the course of the disease and reduce functional loss.

Most of my older patients with SMA have done their research on disease-modifying therapies before coming to see me and recognize that maintenance of motor function is a reasonable goal. I make sure that they have all the right information they need. For Evrysdi, that means reviewing the MFM-32 and the RULM data from the SUNFISH trial, along with the safety information. I want to make sure my patients are making the right decisions for themselves based on the available data.

Shaniqua
I spoke to my doctor about Evrysdi. She was more proactive on me getting on treatment and she actually brought it up to me, saying that "we want to maintain the strength that you do have.” I came to her about the drug and she went back, did her own research on the drug, and then she came back and stated the pros and the cons of Evrysdi. I spoke it over with my mom and my dad and ultimately the decision was mine, whether to take the treatment or not. And I just ultimately decided that it was the best thing for me and that I was very hopeful that it would help. I ultimately chose Evrysdi because it was an oral medication and I was hopeful that it will maintain my strengths.

Dr. Shieh
There's always a discussion about risks and benefits when introducing a new therapy. I use the Evrysdi efficacy data to support the benefits. The data give us reason to believe that the medication will help patients with Type 2 or Type 3 SMA maintain their motor function. Then, to help patients weigh the risks with the benefits, I review potential adverse reactions with the patients before prescribing Evrysdi.

For young women, I review information about pregnancy and potential risks to the fetus. We talk about contraception, and I counsel them to let me know if they're considering starting a family so that we can plan to stop treatment before they become pregnant.

Young men or parents of younger males are interested in learning about possible effects on male fertility. I take the time to review that and discuss options such as sperm preservation. I refer them to a fertility specialist if they're interested.

Shaniqua

When I first began Evrysdi, I had some side effects. It was diarrhea. So I spoke with my doctor and we decided that we would stop taking Evrysdi because I also had another condition that may have been the cause of the diarrhea. A couple months later, after I was treated for that condition, I began taking Evrysdi again, and I did not have diarrhea.

Dr. Shieh

I tell patients that GI side effects are common with Evrysdi and I advise them to take Evrysdi after a full meal.

I tell patients to let me know if they experience GI side effects such as diarrhea so that I can help them work through these symptoms. Some of these issues may be related to Evrysdi while some could be related to SMA itself. We talk about other potential adverse events as well. With all my patients, I review all medications they are taking before starting Evrysdi, including vitamins and over-the counter supplements.

I find that the most helpful way to monitor progress is to listen to what my patients tell me. Are they able to do the things that they could do before they started treatment? Have they experienced any changes? I do use the motor function measurement tools that were used in the clinical trials, but I also want to hear what is clinically meaningful to the patient.

Sometimes I remind patients that not seeing a change doesn't mean the drug is not working. There is a good chance they may not notice an effect, if their motor function is not changing. I reinforce that no change may be the effect we are looking for. Of course, I continue to ask about potential adverse events throughout therapy.

Shaniqua
Since starting Evrysdi, I've seen improvements in my motor function. Being able to cook on my own is really, really important to me because I love to cook. I love to make meals. And also I've seen that it's easier for me to get up out of my chair to a standing position. I notice that I can pick up small objects and open containers with greater ease.

Being able to take my Evrysdi wherever I go, as I'm not confined to taking my medication at one place, just my apartment, because I like to travel.

When I think about Evrysdi, I think about being able to have hope. And every time I take the medication, I'm hoping that the strengths that I do have will be maintained. So, hope.

Taking Evrysdi treatment is important to me because it's me considering my health and how important my health is and me doing something about it. We live in society where there's always an option. And I'm just grateful that there's actually an option, not just one, but many because for so long, the SMA community hasn't had a treatment and a possibility that something will help us. 

I think it's important for healthcare individuals to know that we're still individuals, we're still people. We have feelings just like anyone else. We need more help than others and that's because of our disability. And to just think of us as people and how they would like to be treated, how they would want someone to take care of their family member, their mom or their dad.

Dr. Shieh
I tell prescribers that disease-modifying therapies for SMA are not just for infants or young children. There are data that support the use of disease-modifying therapies in older patients and it is reasonable to give it a try.

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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.

 

 

    • 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.

    • Cure SMA. 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.

      Cure SMA. 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.

    • Darras BT, Boespflug-Tanguy O, Day JW, et al, on behalf of the FIREFISH Working Group. FIREFISH parts 1 and 2: 24-month safety and efficacy of risdiplam in infants with type 1 SMA. Poster presented at: Muscular Dystrophy Association Clinical and Scientifi c Conference; March 13-16, 2022; Nashville, TN.

      Darras BT, Boespflug-Tanguy O, Day JW, et al, on behalf of the FIREFISH Working Group. FIREFISH parts 1 and 2: 24-month safety and efficacy of risdiplam in infants with type 1 SMA. Poster presented at: Muscular Dystrophy Association Clinical and Scientifi c Conference; March 13-16, 2022; Nashville, TN.

    • Cances C, Vlodavets D, Comi GP, et al; ANCHOVY Working Group. Natural history of type 1 spinal muscular atrophy: a retrospective, global, multicenter study. Orphanet J Rare Dis. 2022;17(1):300.

      Cances C, Vlodavets D, Comi GP, et al; ANCHOVY Working Group. Natural history of type 1 spinal muscular atrophy: a retrospective, global, multicenter study. Orphanet J Rare Dis. 2022;17(1):300.

    • 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.

    • Servais L, Oskoui M, Day JW, et al, on behalf of the SUNFISH Study Group. SUNFISH parts 1 and 2: 4-year efficacy and safety of risdiplam in types 2 and 3 spinal muscular atrophy (SMA). Presented at: American Academy of Neurology; April 22-27, 2023; Boston, MA.

      Servais L, Oskoui M, Day JW, et al, on behalf of the SUNFISH Study Group. SUNFISH parts 1 and 2: 4-year efficacy and safety of risdiplam in types 2 and 3 spinal muscular atrophy (SMA). Presented at: American Academy of Neurology; April 22-27, 2023; Boston, MA.

    • 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.

    • Annoussamy M, Seferian AM, Daron A, et al; NatHis-SMA study group. Natural history of Type 2 and 3 spinal muscular atrophy: 2-year NatHis-SMA study. Ann Clin Transl Neurol. 2021;8(2):359-373.doi:10.1002/acn3.51281.

      Annoussamy M, Seferian AM, Daron A, et al; NatHis-SMA study group. Natural history of Type 2 and 3 spinal muscular atrophy: 2-year NatHis-SMA study. Ann Clin Transl Neurol. 2021;8(2):359-373.doi:10.1002/acn3.51281.

    • 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.

    • Darras BT, Boespflug-Tanguy O, Day JW, et al, on behalf of the FIREFISH Working Group. FIREFISH Parts 1 and 2: 24-month safety and efficacy of risdiplam in infants with Type 1 SMA. Poster presented at: Muscular Dystrophy Association Clinical and Scientific Conference; March 13-16, 2022; Nashville, TN.

      Darras BT, Boespflug-Tanguy O, Day JW, et al, on behalf of the FIREFISH Working Group. FIREFISH Parts 1 and 2: 24-month safety and efficacy of risdiplam in infants with Type 1 SMA. Poster presented at: Muscular Dystrophy Association Clinical and Scientific Conference; March 13-16, 2022; Nashville, TN.

    • Finkel RS, Farrar MA, Vlodavets D, et al, on behalf of the RAINBOWFISH Study Group. RAINBOWFISH: Preliminary efficacy and safety data in risdiplam-treated infants with presymptomatic SMA. Poster presented at: Muscular Dystrophy Association Clinical and Scientific Conference; March 13-16, 2022; Nashville, TN.

      Finkel RS, Farrar MA, Vlodavets D, et al, on behalf of the RAINBOWFISH Study Group. RAINBOWFISH: Preliminary efficacy and safety data in risdiplam-treated infants with presymptomatic SMA. Poster presented at: Muscular Dystrophy Association Clinical and Scientific Conference; March 13-16, 2022; Nashville, TN.

    • Baranello G, Day JW, Deconinck N, et al, on behalf of the SUNFISH Working Group. SUNFISH: efficacy and safety of risdiplam in Types 2 and 3 SMA. Poster presented at: European Paediatric Neurology Society; April 28 - May 2, 2022; Glasgow, UK.

      Baranello G, Day JW, Deconinck N, et al, on behalf of the SUNFISH Working Group. SUNFISH: efficacy and safety of risdiplam in Types 2 and 3 SMA. Poster presented at: European Paediatric Neurology Society; April 28 - May 2, 2022; Glasgow, UK.

    • Chiriboga CA, Bruno C, Duong T, et al. JEWELFISH: 24-month safety, pharmacodynamic and exploratory efficacy data in non-treatment-naïve patients with SMA receiving treatment with risdiplam. Presentation at: 2022 Virtual World Muscle Society (WMS) Conference; October 11-15, 2022; Halifax, Canada.

      Chiriboga CA, Bruno C, Duong T, et al. JEWELFISH: 24-month safety, pharmacodynamic and exploratory efficacy data in non-treatment-naïve patients with SMA receiving treatment with risdiplam. Presentation at: 2022 Virtual World Muscle Society (WMS) Conference; October 11-15, 2022; Halifax, Canada.

    • Kletzl H, Cleary Y, Grimsey P, Gerber M, Scalco RS. Risdiplam: pharmacokinetic, pharmacodynamic, safety and efficacy exposure response analyses. Poster presented at: Cure SMA 2022 Research and Clinical Care Meeting; June 15-17, 2022; Anaheim, CA.

      Kletzl H, Cleary Y, Grimsey P, Gerber M, Scalco RS. Risdiplam: pharmacokinetic, pharmacodynamic, safety and efficacy exposure response analyses. Poster presented at: Cure SMA 2022 Research and Clinical Care Meeting; June 15-17, 2022; Anaheim, CA.

    • Iannaccone ST, To TM, Dickendesher T, Shapouri S, Pineda ED. A retrospective analysis of adherence and persistence among risdiplam-treated patients with spinal muscular atrophy (SMA). Poster presented at: Muscular Dystrophy Association Clinical and Scientific Conference; March 19-22, 2023; Dallas, TX.

      Iannaccone ST, To TM, Dickendesher T, Shapouri S, Pineda ED. A retrospective analysis of adherence and persistence among risdiplam-treated patients with spinal muscular atrophy (SMA). Poster presented at: Muscular Dystrophy Association Clinical and Scientific Conference; March 19-22, 2023; Dallas, TX.