Long-Term Risdiplam for Spinal Muscular Atrophy

(WeSMA Trial)

Recruiting at 45 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

402 Participants Needed

Trial Summary

What is the purpose of this trial?

A multi-center, longitudinal, prospective, non-comparative study to investigate the long-term safety and effectiveness of risdiplam, prescribed based on clinician judgment as per the Evrysdi® U.S. Package Insert (USPI) in adult and pediatric participants with SMA. In this study, participants will be followed for the duration of the study or until withdrawal of consent, loss to follow-up, or death. Participants who discontinue risdiplam may still remain in the study, if they agree to continue participating in the follow-up assessments. An optional sub study will assess the feasibility, acceptability, and adherence of remote assessment of motor and bulbar functions in participants with SMA using wearable and smartphone-based biosensors. Approximately 39 participants from the main study are planned to be enrolled in the sub study.

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 data supports the idea that Long-Term Risdiplam for Spinal Muscular Atrophy is an effective drug?

The available research shows that Risdiplam significantly improves motor function in patients with Spinal Muscular Atrophy (SMA). In clinical trials, infants with SMA type 1 and patients aged 2-25 years with SMA types 2 or 3 showed improved motor skills after using Risdiplam. These improvements were maintained for up to two years. Additionally, a systematic review found that after 12 months of treatment, 57% of participants with SMA type 1 achieved better motor function, and those with SMA types 2/3 also showed improvements. Risdiplam is generally well tolerated, making it a convenient and effective option for a wide range of patients. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Risdiplam for treating spinal muscular atrophy?

Risdiplam has been shown to significantly improve motor function in patients with spinal muscular atrophy, including infants with type 1 and patients aged 2-25 years with types 2 or 3. These improvements were maintained for up to 2 years, and the drug is generally well tolerated, providing a convenient oral treatment option. ^{1 2 3 4 5}

What safety data is available for Risdiplam in treating spinal muscular atrophy?

Risdiplam, also known as Evrysdi, has been evaluated for safety in several studies. It is generally well tolerated with a favorable benefit-risk balance. In phase 2/3 clinical trials, it showed significant improvements in motor function for SMA patients and was well tolerated over up to 2 years of treatment. A systematic review and meta-analysis found that 16% of participants experienced adverse events, though serious adverse events were not quantified due to a lack of cases. Overall, the available evidence suggests that Risdiplam is a safe and effective treatment for SMA. ^{1 2 3 4 6}

Is Risdiplam generally safe for humans?

Risdiplam, also known as Evrysdi, has been shown to be generally well tolerated in clinical trials for spinal muscular atrophy, with a favorable balance between benefits and risks. About 16% of participants experienced adverse events, but serious adverse events were not common. ^{1 2 3 4 6}

Is the drug Risdiplam a promising treatment for Spinal Muscular Atrophy?

Yes, Risdiplam is a promising drug for Spinal Muscular Atrophy. It is the first oral medication approved to treat this condition and has shown significant improvements in motor function for patients. It works by increasing the production of a crucial protein that patients with this disease lack. Risdiplam is convenient to use and has been approved for a wide range of ages and types of the disease. ^{1 2 3 5 6}

How is the drug Risdiplam unique in treating spinal muscular atrophy?

Risdiplam is unique because it is the first oral drug for spinal muscular atrophy, making it more convenient than other treatments that require injections. It works by modifying the SMN2 gene to increase the production of a protein essential for muscle function, which is lacking in people with this condition. ^{1 2 3 5 6}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: Substudy Cohort Experimental Treatment 1 Intervention

Participants from the main study will be enrolled in three sub-groups based on their Functional Oral Intake Scale (FOIS) score. Participants will be provided with a preconfigured study smartphone with the spinal muscular atrophy digital assessment tool (SMA-DAT) application and an ADvanced Acousto-Mechanic (ADAM) sensor. Participants will be asked to perform a programmed selection of SMA-DAT tasks for 24 days of the 27-day remote monitoring period.

Group II: Risdiplam Experimental Treatment 1 Intervention

Participants who are taking risdiplam prescribed based on clinician judgment, as per the Evrysdi® USPI are enrolled in this arm.

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

Findings from Research

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]

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 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]

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 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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

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

2. England 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. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Risdiplam: First Approval. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Efficacy of risdiplam in spinal muscular atrophy: A systematic review and meta-analysis. [2023]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Risdiplam Real World Data - Looking Beyond Motor Neurons and Motor Function Measures. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Risdiplam: an investigational survival motor neuron 2 (SMN2) splicing modifier for spinal muscular atrophy (SMA). [2022]