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Onasemnogene Abeparvovec

Onasemnogene Abeparvovec, also known as Zolgensma, is a groundbreaking gene therapy drug being studied in clinical trials for the treatment of Spinal Muscular Atrophy (SMA). These trials aim to assess the long-term safety and effectiveness of the drug in patients who have received it through intravenous (IV) or intrathecal (IT) administration. The studies focus on monitoring adverse events, developmental milestones, motor function, and overall quality of life for patients with SMA over extended periods, ranging from 5 to 15 years.

Table of Contents

What is ONASEMNOGENE ABEPARVOVEC?

ONASEMNOGENE ABEPARVOVEC, also known by its brand name Zolgensma, is a groundbreaking gene therapy medication used to treat Spinal Muscular Atrophy (SMA). It is classified as an advanced therapy medicinal product (ATMP) and specifically as an in vivo gene therapy[1]. This means that the treatment is administered directly into the patient’s body to modify their genetic material.

How Does It Work?

ONASEMNOGENE ABEPARVOVEC works by delivering a functional copy of the SMN1 gene to the patient’s cells. This gene is responsible for producing a protein essential for motor neuron survival. In SMA patients, this gene is missing or defective. The therapy uses a modified virus (AAV9) as a vector to carry the healthy gene into the cells[1]. Once inside, the cells can start producing the necessary protein, potentially improving muscle function and survival in SMA patients.

What Conditions Does It Treat?

ONASEMNOGENE ABEPARVOVEC is specifically designed to treat Spinal Muscular Atrophy (SMA). SMA is a rare genetic disorder that affects muscle strength and movement. There are several types of SMA, including:

  • Spinal muscular atrophy type I (also known as Werdnig-Hoffmann disease)
  • Spinal muscular atrophy type II
  • Spinal muscular atrophy type III (also known as Kugelberg-Welander disease)[2]
This treatment is particularly important for infants and young children diagnosed with SMA, as early intervention can significantly impact the course of the disease.

Administration

ONASEMNOGENE ABEPARVOVEC is administered as a one-time intravenous infusion. The medication comes in the form of a solution for infusion, with a concentration of 2 × 10^13 vector genomes/mL[1]. It’s important to note that this is a single-dose treatment, meaning patients typically receive only one infusion in their lifetime.

Clinical Trials and Research

Extensive research has been conducted to evaluate the safety and efficacy of ONASEMNOGENE ABEPARVOVEC. Clinical trials have included:

  • Phase 1 trials (AVXS-101-CL-102)
  • Phase 3 trials (AVXS-101-CL302, AVXS-101-CL-303, AVXS-101-CL-304, AVXS-101-CL-306)[2]
These trials have involved patients with various types of SMA and have helped establish the treatment’s effectiveness and safety profile.

Long-Term Safety and Efficacy

To better understand the long-term effects of ONASEMNOGENE ABEPARVOVEC, ongoing studies are being conducted. These include:

  1. A 15-year follow-up study to assess long-term safety, focusing on serious adverse events (SAEs) and adverse events of special interest (AESIs)[1].
  2. A study evaluating long-term efficacy through measures such as:
    • Developmental milestones
    • Hammersmith Functional Motor Scale – Expanded (HFMSE) score
    • Revised Upper Limb Module (RULM)
    • Cognitive and language development assessments[2]
These studies aim to provide a comprehensive understanding of how the treatment affects patients over time, including their motor function, cognitive development, and overall quality of life.

Potential Side Effects

As with any medical treatment, ONASEMNOGENE ABEPARVOVEC may cause side effects. The long-term studies are closely monitoring for:

  • Changes in vital signs
  • Alterations in physical examination findings
  • Changes in clinical laboratory assessments
  • Cardiac assessment changes
  • Pulmonary function changes and need for ventilatory support
  • Swallowing dysfunction and need for nutritional support[2]
It’s important for patients and caregivers to discuss potential risks and benefits with their healthcare provider before starting treatment.

Aspect Details
Drug Name Onasemnogene Abeparvovec (Zolgensma)
Condition Treated Spinal Muscular Atrophy (SMA)
Trial Duration Up to 15 years
Primary Objectives Long-term safety and efficacy assessment
Key Assessments Adverse events, motor function, developmental milestones, cognitive function
Administration Routes Intravenous (IV) and Intrathecal (IT)
Participant Eligibility SMA patients previously treated with Onasemnogene Abeparvovec in clinical trials

FAQ

  • What is Onasemnogene Abeparvovec? Onasemnogene Abeparvovec, also known as Zolgensma, is a gene therapy drug designed to treat Spinal Muscular Atrophy (SMA). It works by delivering a functional copy of the SMN1 gene to motor neurons, which is crucial for muscle function and movement.
  • What is the main goal of these clinical trials? The main goal of these clinical trials is to assess the long-term safety and efficacy of Onasemnogene Abeparvovec in patients with SMA. This includes monitoring for serious adverse events, evaluating motor function improvements, and tracking developmental milestones over extended periods.
  • How long do these clinical trials last? The clinical trials have different durations. One study follows patients for up to 15 years, while another has an initial 5-year follow-up phase followed by an observational phase lasting up to 10 years.
  • What types of assessments are done during these trials? The trials include various assessments such as monitoring adverse events, evaluating motor function using scales like the Hammersmith Functional Motor Scale – Expanded (HFMSE) and Revised Upper Limb Module (RULM), tracking developmental milestones, and assessing cognitive function and language development.
  • Who can participate in these clinical trials? Participants in these trials are patients with Spinal Muscular Atrophy who have previously received Onasemnogene Abeparvovec (AVXS-101) in Novartis-sponsored clinical studies. Patients and their caregivers must be willing and able to comply with the study procedures and visit schedules.

Ongoing Clinical Trials on Onasemnogene Abeparvovec

  • Long-term Safety Study of Onasemnogene Abeparvovec for Patients with Spinal Muscular Atrophy

    Not recruiting

    1 1 1 1
    Investigated diseases:
    Investigated drugs:
    Belgium Denmark France Italy The Netherlands Spain

  • Long-term Safety and Efficacy Study of Onasemnogene Abeparvovec in Patients with Spinal Muscular Atrophy

    Not recruiting

    1 1 1 1
    Investigated drugs:
    Belgium France Italy

Glossary

  • Spinal Muscular Atrophy (SMA): A genetic disorder characterized by weakness and wasting in muscles used for movement. It is caused by a loss of specialized nerve cells, called motor neurons, in the spinal cord and the part of the brain that is connected to the spinal cord.
  • Onasemnogene Abeparvovec: A gene therapy drug designed to treat Spinal Muscular Atrophy by delivering a functional copy of the SMN1 gene to motor neurons. It is also known by the brand name Zolgensma.
  • Adverse Events of Special Interest (AESIs): Specific events that are closely monitored during a clinical trial due to their potential significance or relation to the treatment being studied.
  • Hammersmith Functional Motor Scale – Expanded (HFMSE): A standardized test used to assess motor function in patients with Spinal Muscular Atrophy, particularly those with the ability to sit independently.
  • Revised Upper Limb Module (RULM): An assessment tool designed to measure upper limb function in patients with Spinal Muscular Atrophy.
  • Intrathecal (IT) Administration: A method of delivering medication directly into the spinal canal, where it can reach the fluid surrounding the brain and spinal cord.
  • Intravenous (IV) Administration: A method of delivering medication directly into a vein, allowing it to circulate throughout the body via the bloodstream.
  • Developmental Milestone Checklist: A tool used to track and assess a child's progress in achieving key developmental skills and behaviors at specific ages.
  • Gene Therapy: A technique that uses genes to treat or prevent disease. In the case of SMA, it involves delivering a functional copy of the SMN1 gene to motor neurons.
  • SMN1 Gene: The Survival Motor Neuron 1 gene, which is responsible for producing a protein essential for the survival and function of motor neurons. Mutations in this gene cause Spinal Muscular Atrophy.

References

  1. http://clinicaltrials.eu/trial/long-term-safety-study-of-onasemnogene-abeparvovec-for-patients-with-spinal-muscular-atrophy/
  2. http://clinicaltrials.eu/trial/long-term-safety-and-efficacy-study-of-onasemnogene-abeparvovec-in-patients-with-spinal-muscular-atrophy/