OAV101 for Spinal Muscular Atrophy

(SPECTRUM Trial)

Recruiting at 27 trial locations

Overseen By Novartis Gene Therapies Med Info (Europe, Middle East, Africa, Asia-Pacific)

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

175 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.

What data supports the effectiveness of the treatment Onasemnogene abeparvovec (Zolgensma) for Spinal Muscular Atrophy?

Research shows that Onasemnogene abeparvovec (Zolgensma) is effective in treating spinal muscular atrophy (SMA), especially when given early, as it can change the course of the disease and improve survival rates in infants. Studies have demonstrated that this gene therapy helps deliver a missing gene that is crucial for muscle movement, leading to better outcomes in young patients with SMA. ^{1 2 3 4 5}

What safety data exists for OAV101 (Onasemnogene abeparvovec) in humans?

Onasemnogene abeparvovec, also known as Zolgensma, has been studied for safety in infants with spinal muscular atrophy (SMA). Research shows it is generally safe, but like any treatment, it may have side effects, and its safety is evaluated in real-world practice and clinical trials. ^{1 2 3 4 5}

What makes the treatment Onasemnogene abeparvovec unique for spinal muscular atrophy?

Onasemnogene abeparvovec is unique because it is a one-time gene therapy that addresses the genetic root cause of spinal muscular atrophy by delivering a working copy of the SMN1 gene directly into the patient's cells through a single intravenous infusion. This approach is different from other treatments as it aims to replace the function of the missing or nonworking gene, leading to rapid improvements in motor function and developmental milestones. ^{3 4 6 7 8}

What is the purpose of this trial?

This is a global, prospective, multi-center study that is designed to assess the long-term safety and efficacy of OAV101 in patients who participated in an OAV101 clinical trial. The assessments of safety and efficacy in Study COAV101A12308 will continue for 5 years after enrollment in this study.

Eligibility Criteria

This trial is for patients who have previously taken part in a clinical study involving OAV101, a gene therapy for spinal muscular atrophy. Participants must provide written consent and be able to follow the study's procedures as directed by their doctor or legal guardian.

Inclusion Criteria

Participated in an OAV101 clinical trial

Patient/Parent/legal guardian willing and able to comply with study procedures

Written informed consent must be obtained before any assessment is performed

Exclusion Criteria

There are no exclusion criteria for this study.

Timeline

Baseline

All patients will enter the study at the baseline visit

1 visit

1 visit (in-person)

Follow-up Period 1

Participants are monitored every 6 months for the first 2 years

2 years

4 visits (in-person)

Follow-up Period 2

Participants are monitored annually for years 3 to 5

3 years

3 visits (in-person)

Treatment Details

Interventions

• Onasemnogene abeparvovec

Trial Overview The long-term safety and effectiveness of onasemnogene abeparvovec (OAV101) are being studied over a period of 15 years in individuals with spinal muscular atrophy who received this treatment during earlier trials.

Participant Groups

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

Patients who received OAV101 IT or OAV101 IV in clinical trials (COAV101A12306, COAV101B12301 and COAV101B12302)

Onasemnogene abeparvovec is already approved in United States, European Union for the following indications:

Approved in United States as Zolgensma for:

• Spinal muscular atrophy (SMA) in pediatric patients less than 2 years of age with bi-allelic mutations in the SMN1 gene

Approved in European Union as Zolgensma for:

• Spinal muscular atrophy (SMA) in patients with inherited mutations affecting the SMN1 gene, who have either been diagnosed with SMA type 1 or have up to 3 copies of the SMN2 gene

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

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 phase 3 trial involving 22 infants with spinal muscular atrophy type 1, 59% achieved independent sitting for 30 seconds or longer by 18 months, compared to 0% in an untreated cohort, demonstrating significant efficacy of the gene therapy onasemnogene abeparvovec.

91% of treated patients survived without the need for permanent ventilation by 14 months, highlighting the therapy's potential to improve survival outcomes compared to only 26% in the untreated group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Onasemnogene abeparvovec gene therapy for symptomatic infantile-onset spinal muscular atrophy in patients with two copies of SMN2 (STR1VE): an open-label, single-arm, multicentre, phase 3 trial. Day, JW., Finkel, RS., Chiriboga, CA., et al.[2021]

Onasemnogene abeparvovec-xioi (Zolgensma) is a gene therapy approved for treating spinal muscular atrophy (SMA) in children under 2 years old, providing a one-time treatment that delivers the SMN1 gene to help produce the SMN protein.

While it shows efficacy in younger patients with SMA type 1, there are concerns regarding its high cost and potential liver toxicity, and the long-term benefits and risks are still unknown.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Onasemnogene Abeparvovec-xioi: Gene Therapy for Spinal Muscular Atrophy. Stevens, D., Claborn, MK., Gildon, BL., et al.[2021]

Onasemnogene abeparvovec (Zolgensma®) has been approved for treating spinal muscular atrophy (SMA) in patients with up to three copies of the SMN2 gene or those with SMA type 1, marking a significant advancement in treatment options.

The paper outlines eleven consensus statements from European neuromuscular experts to guide the safe and effective use of Zolgensma®, focusing on patient selection, safety, and long-term monitoring, especially emphasizing the importance of early treatment initiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

European ad-hoc consensus statement on gene replacement therapy for spinal muscular atrophy. Kirschner, J., Butoianu, N., Goemans, N., et al.[2021]

Onasemnogene abeparvovec (Zolgensma®) is a one-time gene therapy approved for treating spinal muscular atrophy (SMA) in patients under 2 years old, effectively replacing the missing SMN1 gene and leading to significant improvements in motor function and survival rates not seen in untreated SMA patients.

Clinical trials, including Phase I and III studies, demonstrated that patients often showed rapid improvements in motor skills within a month of treatment, although some experienced mild side effects like elevated liver enzymes, which were manageable with medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacological and clinical profile of Onasemnogene Aveparvovec, the first gene therapy for spinal muscular atrophy (SMA)]. Atsumi, A., Yoneda, T., Tsuchida, K., et al.[2022]

Onasemnogene abeparvovec, also known as ZOLGENSMA®, is the first gene therapy approved in the USA for treating spinal muscular atrophy (SMA) in children under 2 years old, targeting the underlying genetic cause by delivering a functional SMN gene.

The therapy is administered as a single intravenous infusion at a dose of 1.1 × 10^14 vector genomes per kg, highlighting its innovative approach to potentially improve motor neuron function in patients with SMA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Onasemnogene Abeparvovec: First Global Approval. Hoy, SM.[2020]

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]

References

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

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

2. 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]

3. England pubmed.ncbi.nlm.nih.gov

Onasemnogene abeparvovec gene therapy for symptomatic infantile-onset spinal muscular atrophy in patients with two copies of SMN2 (STR1VE): an open-label, single-arm, multicentre, phase 3 trial. [2021]

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

Onasemnogene Abeparvovec-xioi: Gene Therapy for Spinal Muscular Atrophy. [2021]

5. England pubmed.ncbi.nlm.nih.gov

European ad-hoc consensus statement on gene replacement therapy for spinal muscular atrophy. [2021]

6. Japan pubmed.ncbi.nlm.nih.gov

[Pharmacological and clinical profile of Onasemnogene Aveparvovec, the first gene therapy for spinal muscular atrophy (SMA)]. [2022]

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

Onasemnogene Abeparvovec: First Global Approval. [2020]

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

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