Long-Term Risdiplam for Spinal Muscular Atrophy

(WeSMA Trial)

Not currently recruiting at 49 trial locations

Overseen By Reference Study ID Number: ML43702 https://forpatients.roche.com/

Age: Any Age

Sex: Any

Trial Phase: Phase 4

Sponsor: Genentech, Inc.

Must be taking: Risdiplam

Disqualifiers: Hypersensitivity to risdiplam, Schizophrenia, Bipolar, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 9 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 27

Duration: Up to approximately 4.5 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the long-term safety and effectiveness of risdiplam, a medication for individuals with spinal muscular atrophy (SMA). Participants will continue taking risdiplam as prescribed by their doctors and will be monitored over time. The trial also includes an optional sub-study using smartphone and wearable sensors to remotely assess motor and swallowing functions. Individuals diagnosed with SMA and already taking risdiplam might be suitable candidates for this study. As a Phase 4 trial, this research aims to understand how the FDA-approved treatment benefits a broader range of patients.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications. It is best to discuss this with your doctor.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It seems that you can continue taking risdiplam if prescribed, but it's best to discuss your specific situation with the trial team or your doctor.

What is the safety track record for Risdiplam?

Research has shown that risdiplam is generally safe for people with spinal muscular atrophy (SMA). In studies, no safety issues related to the treatment have caused participants to stop using risdiplam. This includes a large group of 465 patients across different trials. The safety profile, summarizing the drug's safety, appears consistent for both infants and older patients, indicating similar safety across age groups. Additionally, those who switched from another SMA treatment to risdiplam experienced positive safety outcomes. Overall, risdiplam is well-tolerated, with no major safety concerns reported. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Risdiplam is unique because it is an oral treatment that continuously delivers benefits to patients with spinal muscular atrophy (SMA) by enhancing and maintaining the production of the SMN protein, which is crucial for motor neuron health. Unlike traditional SMA treatments that may require invasive administration methods like injections, risdiplam offers the convenience of an oral liquid, making it easier for patients, especially children, to adhere to their regimen. Researchers are particularly excited about risdiplam’s ability to provide systemic benefits, potentially improving overall motor function, and quality of life for those living with SMA.

What is the effectiveness track record for risdiplam in treating spinal muscular atrophy?

Research has shown that risdiplam, which participants in this trial may receive, effectively treats spinal muscular atrophy (SMA). In studies, both adults and children with SMA Types 2 and 3 experienced improved motor skills and better use of their arms and hands after taking risdiplam. As the first oral medication approved for SMA, it helps the body produce more of a protein essential for muscle function. Over five years, 91% of children taking risdiplam were alive, whereas those with untreated Type 1 SMA often do not survive past early childhood. These findings highlight risdiplam's potential to greatly enhance the quality of life for people with SMA. ^{6 7 8 9 10}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

This trial is for both adults and children with a confirmed diagnosis of 5q-autosomal recessive Spinal Muscular Atrophy (SMA). Participants must be prescribed risdiplam based on their doctor's judgment. Those allergic to risdiplam or who were in previous registrational trials for the drug cannot join.

Inclusion Criteria

I have been diagnosed with 5q-autosomal recessive SMA.

I have been prescribed risdiplam after its FDA approval on 07 August 2020.

Exclusion Criteria

You have been part of a specific trial for risdiplam.

You are allergic to risdiplam.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive risdiplam treatment as prescribed based on clinician judgment

Up to approximately 4.5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 4.5 years

Substudy

Remote assessment of motor and bulbar functions using wearable and smartphone-based biosensors

9 weeks

Remote monitoring for 27 days

What Are the Treatments Tested in This Trial?

Interventions

• Risdiplam

Trial Overview

The study is looking at the long-term safety and effectiveness of a medication called Risdiplam in patients with SMA. It's not comparing it to other treatments, but just following those taking it for up to five years to see how they do over time.

How Is the Trial Designed?

Group I: Risdiplam Experimental Treatment 1 Intervention

Participants who are taking risdiplam prescribed based on clinician judgment, as per the Evrysdi® USPI are enrolled in this study. A Remote Virtual Site option is available in the study allowing enrollment of participants with SMA who are prescribed risdiplam treatment even if their physician is not a participating investigator. A central investigator will be responsible for data collection and data entry for participants who do not have a participating investigator.

Risdiplam is already approved in United States, European Union, Brazil, China for the following indications:

Approved in United States as Evrysdi for:

• Spinal muscular atrophy (SMA) in patients 2 months of age and older

Approved in European Union as Evrysdi for:

• 5q-autosomal recessive SMA with a clinical diagnosis of SMA types 1, 2, or 3 or with one to four survival motor neuron 2 (SMN2) copies

Approved in Brazil as Evrysdi for:

• Spinal muscular atrophy (SMA)

Approved in China as Evrysdi for:

• Spinal muscular atrophy (SMA)

Who Is Running the Clinical Trial?

Genentech, Inc.

Lead Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Published Research Related to This Trial

In a real-world study of 31 adult patients with spinal muscular atrophy types 2 and 3, risdiplam was well tolerated, with most patients reporting no side effects and some experiencing clinically meaningful improvements in motor function and quality of life.

The treatment not only stabilized motor functions but also led to unexpected benefits such as weight gain and improved appetite in a third of the patients, highlighting the need for monitoring effects beyond just neuromuscular outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risdiplam Real World Data - Looking Beyond Motor Neurons and Motor Function Measures. Sitas, B., Hancevic, M., Bilic, K., et al.[2023]

Risdiplam treatment for spinal muscular atrophy (SMA) showed significant efficacy, with 57% of participants with SMA type 1 achieving a CHOP-INTEND score of 40 or higher after 12 months, indicating improved motor function.

In SMA types 2 and 3, motor function measures (MFM32, RULM, HFMSE) increased significantly, although respiratory function improvements were inconsistent, and 16% of participants experienced adverse events, suggesting risdiplam is generally safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of risdiplam in spinal muscular atrophy: A systematic review and meta-analysis. Pascual-Morena, C., Martínez-Vizcaíno, V., Cavero-Redondo, I., et al.[2023]

Risdiplam (Evrysdi™) is an oral medication that modifies RNA splicing to enhance the production of functional SMN protein, addressing the deficiency caused by spinal muscular atrophy (SMA).

In August 2020, risdiplam received FDA approval for treating SMA in patients as young as 2 months old, and it is currently in the pre-registration phase in several countries, indicating its potential global impact on SMA treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risdiplam: First Approval. Dhillon, S.[2021]

Risdiplam is the first oral medication approved for spinal muscular atrophy (SMA) and has shown disease-modifying potential, acting as a splicing modifier for the SMN2 gene, which is crucial for motor neuron survival.

Clinical trials have demonstrated risdiplam's efficacy across SMA Types 1, 2, and 3, with a satisfactory safety profile, although its comparative effectiveness against other approved SMA treatments remains to be established.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risdiplam: an investigational survival motor neuron 2 (SMN2) splicing modifier for spinal muscular atrophy (SMA). Markati, T., Fisher, G., Ramdas, S., et al.[2022]

Risdiplam (Evrysdi®) is the first oral medication approved for treating spinal muscular atrophy (SMA) in patients aged 2 months and older, specifically targeting the production of the SMN protein essential for motor function.

In phase 2/3 clinical trials, risdiplam significantly improved motor function in infants with SMA type 1 and patients aged 2-25 years with SMA types 2 or 3, with benefits maintained for up to 2 years, and it was generally well tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risdiplam: A Review in Spinal Muscular Atrophy. Paik, J.[2022]

In a phase 3 study involving 180 patients aged 2-25 with type 2 or non-ambulant type 3 spinal muscular atrophy, risdiplam significantly improved motor function compared to placebo, with a treatment difference of 1.55 points on the Motor Function Measure at 12 months (p=0.016).

While risdiplam was generally well-tolerated, it was associated with a higher incidence of certain adverse events, such as pyrexia and diarrhea, compared to placebo, but serious adverse events were similar between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of once-daily risdiplam in type 2 and non-ambulant type 3 spinal muscular atrophy (SUNFISH part 2): a phase 3, double-blind, randomised, placebo-controlled trial. Mercuri, E., Deconinck, N., Mazzone, ES., et al.[2022]

Citations

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evrysdi.com

evrysdi.com/results-with-evrysdi/results-in-adults-and-children.html

Powerful results in adults and children with Type 2 and 3 ...

Adults and children improved their motor skills and upper limb function when taking Evrysdi, an at-home treatment. SUNFISH is a 2-part, placebo-controlled ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8567805/

Risdiplam for the Use of Spinal Muscular Atrophy - PMC

Risdiplam is the first and only oral medication to be approved to treat SMA. As an SMN2 splicing modifier, it has provided stronger systemic therapies.

3.

roche.com

roche.com/media/releases/med-cor-2024-06-07

Five-year data for Roche's Evrysdi show the majority of ...

After five years of treatment, 91% of children were alive — without treatment, children with Type 1 SMA would not be expected to live past ...

4.

thelancet.com

thelancet.com/journals/eclinm/article/PIIS2589-5370(25)00469-9/fulltext

Efficacy and safety of risdiplam in adults with 5q-associated ...

Importantly, HFMSE outcome was not significantly influenced by treatment centre. n, Mean change from baseline (95% CI), p-value. Spinal muscular ...

5.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02908685

NCT02908685 | A Study to Investigate the Safety, ...

A positive change from Baseline indicates improvement. MMRM analysis was performed based on primary efficacy hypothetical estimand, which included participants ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39136364/

Safety of risdiplam in spinal muscular atrophy patients after ...

Our study showed good safety data on patients who received risdiplam following nusinersen within the washout period of 90 days.

7.

evrysdi-hcp.com

evrysdi-hcp.com/safety/safety-profile.html

Evrysdi® (risdiplam) Safety Profile |Official Healthcare ...

Review the safety information, adverse reactions data and side effects of Evrysdi® (risdiplam) in clinical trials treating Spinal Muscular Atrophy (SMA).

8.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0960896623002924

Risdiplam clinical trial program for spinal muscular atrophy ...

Risdiplam has a favorable safety profile, with no treatment-related adverse events (AEs) leading to treatment withdrawal.

9.

evrysdi.com

evrysdi.com/

Evrysdi® (risdiplam) | Spinal Muscular Atrophy (SMA ...

The safety profile of presymptomatic infants is consistent with the safety profile for symptomatic SMA patients treated with Evrysdi in clinical studies.

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jnnp.bmj.com

jnnp.bmj.com/content/93/9/e2.142

182 Pooled safety data from the risdiplam clinical ...

Pooled analyses from FIREFISH, SUNFISH and JEWELFISH showed no treatment-related safety findings leading to withdrawal from risdiplam in 465 patients treated ...