Risdiplam for Spinal Muscular Atrophy

(HINALEA 1 Trial)

Recruiting at 17 trial locations

Overseen By Reference Study ID Number: BN44620 https://forpatients.roche.com/

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: Hoffmann-La Roche

Must not be taking: Antisense oligonucleotides, Splicing modifiers

Disqualifiers: Invasive ventilation, Tracheostomy, Feeding tube, others

No Placebo Group

Prior Safety Data

Approved in 9 Jurisdictions

Trial Summary

What is the purpose of this trial?

This is an open-label, single-arm, multicenter clinical study to evaluate the effectiveness and safety of risdiplam administered as an early intervention in pediatric participants with spinal muscular atrophy (SMA) and 2 SMN2 copies who have previously received onasemnogene abeparvovec. Participants are children \< 2 years of age genetically diagnosed with SMA.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you have been treated with certain investigational therapies or SMN2-targeting drugs before the study.

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 types 2 and 3, with improvements maintained for up to 2 years. In a study, 32% of patients showed improvement in motor function scores after 24 months, and 58% showed stabilization, indicating the drug's effectiveness in managing the condition. ^{1 2 3 4 5}

Is Risdiplam safe for humans?

Risdiplam, also known as Evrysdi, has been 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 6 7}

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 4 8}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for children under 2 years old with spinal muscular atrophy (SMA) who have two SMN2 gene copies and received onasemnogene abeparvovec. They should not have had a significant decline in function since receiving the gene therapy between 3 to 7 months before joining.

Inclusion Criteria

My health hasn't worsened significantly since my last treatment.

I have received onasemnogene abeparvovec either before or after showing symptoms.

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

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive risdiplam orally once daily for 72 weeks

72 weeks

Treatment Extension

Participants continue to receive risdiplam for an additional 1-year period

48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Risdiplam (SMN2 Splicing Modifier)

Trial Overview The study tests risdiplam's effectiveness and safety as an early treatment for SMA in kids who've already had gene therapy. It's an open-label, single-arm trial, meaning all participants receive risdiplam without being compared to a placebo or other treatment.

Participant Groups

Group I: Risdiplam Experimental Treatment 1 Intervention

Participants will receive risdiplam orally once daily for 72 weeks (Treatment Period). The Treatment Period will be followed by a 1-year Treatment Extension Period for a total study duration of 120 weeks (approximately 2.5 years) for each participant enrolled.

Risdiplam is already approved in Brazil, China for the following indications:

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?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Findings from Research

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 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]

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]

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]

In a Phase 3 study involving patients with type 2 and non-ambulant type 3 spinal muscular atrophy (SMA), risdiplam significantly improved motor function after 12 months, with 32% of patients showing improvement and 58% stabilizing their condition by month 24.

The safety profile of risdiplam remained consistent over 24 months, confirming its long-term efficacy and safety as a treatment for SMA, with continued benefits observed in motor function compared to an external comparator.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-year efficacy and safety of risdiplam in patients with type 2 or non-ambulant type 3 spinal muscular atrophy (SMA). Oskoui, M., Day, JW., Deconinck, N., 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 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]

In the FIREFISH study involving 41 infants with type 1 spinal muscular atrophy, 44% of participants were able to sit without support for at least 30 seconds after 24 months of treatment with risdiplam, showing significant improvement compared to untreated infants.

While no infants were able to stand or walk alone after 24 months, the treatment was generally well-tolerated, with upper respiratory infections being the most common adverse event, indicating a need for ongoing monitoring of long-term safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of risdiplam in patients with type 1 spinal muscular atrophy (FIREFISH part 2): secondary analyses from an open-label trial. Masson, R., Mazurkiewicz-Bełdzińska, M., Rose, K., et al.[2022]

References

1. 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]

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

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

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

Risdiplam: First Approval. [2021]

4. Netherlands pubmed.ncbi.nlm.nih.gov

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

5. Germany pubmed.ncbi.nlm.nih.gov

Two-year efficacy and safety of risdiplam in patients with type 2 or non-ambulant type 3 spinal muscular atrophy (SMA). [2023]

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

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

7. England pubmed.ncbi.nlm.nih.gov

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

8. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of risdiplam in patients with type 1 spinal muscular atrophy (FIREFISH part 2): secondary analyses from an open-label trial. [2022]