Long-term Follow-up with Onasemnogene Abeparvovec-xioi for Spinal Muscular Atrophy

Recruiting at 31 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Gene Therapies

Disqualifiers: Parent unwilling to participate

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: Varies based on parent study

85 Participants Needed

Trial Summary

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's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Onasemnogene Abeparvovec-xioi for Spinal Muscular Atrophy?

Research shows that Onasemnogene Abeparvovec-xioi, a gene replacement therapy, has been effective in improving outcomes for infants with spinal muscular atrophy, particularly those under two years old. Studies highlight its long-term safety and positive impact on patient and caregiver experiences. ^{1 2 3 4 5}

Is Onasemnogene Abeparvovec-xioi safe for humans?

Onasemnogene Abeparvovec-xioi has been studied for safety in infants with spinal muscular atrophy, showing it is generally safe, but like any treatment, it may have side effects. It is the only approved gene-replacement therapy for this condition, and ongoing studies continue to monitor its long-term safety. ^{1 2 3 4 6}

How is the drug Onasemnogene Abeparvovec-xioi unique for treating spinal muscular atrophy?

Onasemnogene Abeparvovec-xioi is unique because it is a gene replacement therapy that delivers a fully functional copy of the survival motor neuron gene, addressing the genetic root cause of spinal muscular atrophy. It is administered as a one-time intravenous infusion, which is different from other treatments that may require ongoing administration. ^{1 2 3 4 7}

What is the purpose of this trial?

This is a long-term follow-up safety and efficacy study of participants in clinical trials for spinal muscular atrophy (SMA) who were treated with onasemnogene abeparvovec-xioi. Participants will roll over from their respective previous (parent) study into this long-term study for continuous monitoring of safety as well as monitoring of continued efficacy and durability of response to onasemnogene abeparvovec-xioi treatment.

Research Team

Sitra Tauscher-Wisniewski, MD

Principal Investigator

Novartis Gene Therapies, Inc.

Eligibility Criteria

This trial is for patients with Spinal Muscular Atrophy who previously received the gene therapy onasemnogene abeparvovec-xioi in a Novartis-sponsored study. Participants or their guardians must consent to and follow the study's procedures.

Inclusion Criteria

I have SMA and was treated with onasemnogene abeparvovec-xioi in a Novartis study.

Participant/parent/legal guardian willing and able to complete the informed consent process and comply with study procedures and visit schedule

I have SMA and was treated with onasemnogene abeparvovec-xioi in a Novartis study.

Exclusion Criteria

Parent/legal guardian unable or unwilling to participate in the long-term follow-up safety study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants received treatment with IV or IT onasemnogene abeparvovec-xioi in their respective parent study

Varies based on parent study

Long-term Follow-up

Continuous monitoring of safety, efficacy, and durability of response to onasemnogene abeparvovec-xioi treatment

Up to 15 years

Treatment Details

Interventions

• Onasemnogene Abeparvovec-xioi

Trial Overview The long-term safety and effectiveness of onasemnogene abeparvovec-xioi, a gene replacement therapy for SMA, are being monitored as participants transition from earlier trials for ongoing evaluation.

Participant Groups

Group I: Intravenous (IV) & Intrathecal (IT) Onasemnogene Abeparvovec-xioi Experimental Treatment 1 Intervention

Participants received treatment with IV onasemnogene abeparvovec-xioi in an onasemnogene abeparvovec-xioi or received treatment with IT onasemnogene abeparvovec-xioi in an onasemnogene.

Who Is Running the Clinical Trial?

Novartis Gene Therapies

Lead Sponsor

Trials

9

Recruited

45,200+

Findings from Research

In a study of 21 infants with spinal muscular atrophy (SMA) treated with onasemnogene abeparvovec, 76% achieved at least one World Health Organization motor milestone, indicating significant efficacy in improving motor function.

All children experienced transient side effects, with vomiting being universal and moderate to severe transaminitis occurring more frequently in infants weighing 8 kg or more, highlighting the importance of monitoring and individualized management for safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Onasemnogene abeparvovec in spinal muscular atrophy: an Australian experience of safety and efficacy. D'Silva, AM., Holland, S., Kariyawasam, D., et al.[2022]

Onasemnogene abeparvovec (OA) demonstrated significant efficacy in improving motor function in infants with Spinal Muscular Atrophy across a wide age range (22 days to 72 months) and weight range (3.2 to 17 kg), with notable improvements seen as early as 3 months in patients treated before 24 months of age.

The study identified that older age at treatment was a predictor of elevated transaminase levels, indicating a higher risk of liver-related side effects, which should be considered when selecting patients for OA therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Onasemnogene abeparvovec in spinal muscular atrophy: predictors of efficacy and safety in naïve patients with spinal muscular atrophy and following switch from other therapies. Pane, M., Berti, B., Capasso, A., et al.[2023]

In a real-world study of 64 patients treated with onasemnogene abeparvovec (OA) for spinal muscular atrophy (SMA), those treated at 6-23 months of age achieved higher motor milestones, such as 100% sitting without support and 58.8% walking with assistance, compared to non-treated patients.

OA-treated patients experienced fewer hospitalizations and surgeries, with none requiring tracheostomy or prolonged use of breathing support, indicating a potential improvement in overall health outcomes and caregiver quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient and Caregiver Outcomes After Onasemnogene Abeparvovec Treatment: Findings from the Cure SMA 2021 Membership Survey. Toro, W., Yang, M., Georgieva, M., et al.[2023]

Onasemnogene abeparvovec, the first approved gene-replacement therapy for spinal muscular atrophy, has been shown to have manageable safety risks, with 101 out of 102 patients experiencing at least one treatment-emergent adverse event (AE) during clinical trials.

Key safety concerns include hepatotoxicity, which resolved with treatment, and transient decreases in platelet counts, while thrombotic microangiopathy (TMA) was noted in postmarketing data, indicating the need for monitoring and potential medical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Trial and Postmarketing Safety of Onasemnogene Abeparvovec Therapy. Day, JW., Mendell, JR., Mercuri, E., et al.[2022]

References

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

Real-Life Outcome After Gene Replacement Therapy for Spinal Muscular Atrophy: A Multicenter Experience. [2023]

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

Five-Year Extension Results of the Phase 1 START Trial of Onasemnogene Abeparvovec in Spinal Muscular Atrophy. [2022]

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

Onasemnogene abeparvovec in spinal muscular atrophy: an Australian experience of safety and efficacy. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Onasemnogene abeparvovec in spinal muscular atrophy: predictors of efficacy and safety in naïve patients with spinal muscular atrophy and following switch from other therapies. [2023]

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

Patient and Caregiver Outcomes After Onasemnogene Abeparvovec Treatment: Findings from the Cure SMA 2021 Membership Survey. [2023]

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

Clinical Trial and Postmarketing Safety of Onasemnogene Abeparvovec Therapy. [2022]

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

Adeno-associated virus serotype 9 antibodies in patients screened for treatment with onasemnogene abeparvovec. [2021]