OAV101 for Spinal Muscular Atrophy

(SPECTRUM Trial)

Recruiting at 33 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to study the long-term effects of Onasemnogene Abeparvovec (OAV101) for individuals with Spinal Muscular Atrophy (SMA), a condition that progressively weakens muscles. Researchers seek to evaluate the safety and effectiveness of this treatment over five years. Participants must have previously taken part in an OAV101 clinical trial. Those who have participated in an OAV101 trial and can commit to study procedures may be suitable for this research. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment for SMA.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

Is there any evidence suggesting that OAV101 is likely to be safe for humans?

Research has shown that onasemnogene abeparvovec, the treatment under study, has a safety record that supports its use. While some side effects occur, they are usually manageable. Common side effects include increased liver enzymes, fever, vomiting, and low platelet levels, which are the most frequently reported issues among patients.

Recent findings from a large study showed positive safety results for onasemnogene abeparvovec when administered directly into the spinal fluid, supporting its continued use in treating spinal muscular atrophy.

In summary, although some side effects exist, onasemnogene abeparvovec has demonstrated a good safety record in studies so far. These findings are encouraging as more research continues. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Onasemnogene abeparvovec for treating Spinal Muscular Atrophy (SMA) because it offers a groundbreaking approach to therapy. Unlike existing treatments like nusinersen and risdiplam, which require repeated doses and work by modifying RNA, Onasemnogene abeparvovec is a one-time gene therapy. It delivers a functional copy of the SMN1 gene directly to the patient's cells, potentially providing lasting benefits. This novel delivery method could significantly reduce the treatment burden and improve quality of life for patients with SMA.

What evidence suggests that OAV101 might be an effective treatment for spinal muscular atrophy?

Research shows that onasemnogene abeparvovec holds promise for treating spinal muscular atrophy (SMA). Studies have found that this treatment greatly improves important health outcomes, with many patients experiencing better movement and muscle function. Real-world evidence supports these findings, showing that patients who receive the therapy often see significant benefits. In this trial, participants will receive onasemnogene abeparvovec either intravenously or as a spinal fluid injection. Recent studies reported positive safety and effectiveness for the spinal fluid injection version, especially in children and young adults with SMA. Overall, the treatment has been consistently effective, with only a few serious side effects reported. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 (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]

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]

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 (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]

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, 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]

Citations

1. curesma.org curesma.org/novartis-intrathecal-gene-therapy-topline-results-december2024/

Novartis Intrathecal Gene Therapy Onasemnogene ... This pivotal study assessed the efficacy and safety of investigational intrathecal onasemnogene abeparvovec (OAV101 IT) in treatment-naïve patients with spinal ...

2. novartis.com novartis.com/news/media-releases/new-novartis-phase-iii-data-demonstrate-meaningful-efficacy-and-safety-results-intrathecal-onasemnogene-abeparvovec-broad-patient-population-sma

New Novartis Phase III data demonstrate meaningful ... Novartis announced positive safety and efficacy results from the Phase III program for investigational intrathecal onasemnogene abeparvovec (OAV101 IT)

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05089656

NCT05089656 | Efficacy and Safety of Intrathecal OAV101 ... A randomized, sham-controlled, double-blind study to evaluate the efficacy and safety of intrathecal OAV101 in type 2 spinal muscular atrophy (SMA) patients.

4. novartis.com novartis.com/news/media-releases/novartis-intrathecal-onasemnogene-abeparvovec-phase-iii-study-meets-primary-endpoint-children-and-young-adults-sma

Novartis intrathecal onasemnogene abeparvovec Phase III ... This pivotal study assessed the efficacy and safety of investigational intrathecal onasemnogene abeparvovec (OAV101 IT) in treatment-naïve patients with spinal ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10977451/

Real-World Outcomes in Patients with Spinal Muscular ... We sought to describe patients with SMA treated with onasemnogene abeparvovec monotherapy in the real-world setting.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38543180/

Real-World Safety Data of the Orphan Drug ... Out of a total of 2744 reported ADRs, increased hepatic enzymes, pyrexia, vomiting, and thrombocytopenia were the most commonly reported adverse reactions.

7. thelancet.com thelancet.com/journals/lanam/article/PIIS2667-193X(25)00203-0/fulltext

Safety and tolerability of onasemnogene abeparvovec ... Clinical trials have demonstrated the safety and efficacy of treatments for patients with spinal muscular atrophy (SMA); however, most of these studies, ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S266677622400259X

Efficacy and safety of gene therapy with onasemnogene ... This observational study included individuals with Spinal Muscular Atrophy (SMA) treated with OA in 29 specialized neuromuscular centers in the DA-CH-region.

9. mdpi.com mdpi.com/1424-8247/17/3/394

Real-World Safety Data of the Orphan Drug ... Safety Concerns with Nusinersen, Risdiplam, and Onasemnogene Abeparvovec in Spinal Muscular Atrophy: A Real-World Pharmacovigilance Study.