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Avalotcagene Ontaparvovec

Avalotcagene Ontaparvovec is an innovative gene therapy being studied in clinical trials for the treatment of late-onset Ornithine Transcarbamylase (OTC) deficiency. This rare genetic disorder affects the body’s ability to process nitrogen, leading to potentially dangerous ammonia buildup in the blood. The clinical trials aim to evaluate the safety and effectiveness of this therapy in improving OTC function and maintaining safe ammonia levels in patients aged 12 and older.

Table of Contents

What is Avalotcagene Ontaparvovec?

Avalotcagene ontaparvovec, also known by its product codes DTX301 or SCAAV8OTC, is an innovative gene therapy designed to treat a rare genetic disorder[1]. It is classified as an advanced therapy medicinal product, specifically a gene therapy medicinal product[2].

What Condition Does It Treat?

Avalotcagene ontaparvovec is being developed to treat late-onset ornithine transcarbamylase (OTC) deficiency[1]. OTC deficiency is a rare genetic disorder that affects the urea cycle, a process in the body that removes ammonia from the blood. People with this condition can’t properly process nitrogen, leading to a dangerous build-up of ammonia in the blood (hyperammonemia)[2].

How Does It Work?

This therapy uses a recombinant adeno-associated virus serotype 8 (AAV8) vector to deliver a functional copy of the OTC gene to the patient’s liver cells[2]. The AAV8 vector is a modified virus that can’t cause disease but can efficiently deliver genetic material to cells. Once inside the liver cells, this gene should enable the production of the OTC enzyme, potentially correcting the underlying cause of the disease.

Clinical Trials

Avalotcagene ontaparvovec is currently being studied in clinical trials:

  • A long-term follow-up study (Phase I/II) is evaluating the safety and efficacy of a single intravenous dose in adults with late-onset OTC deficiency over a period of up to 416 weeks (8 years)[1].
  • A Phase 3 randomized, double-blind, placebo-controlled study is ongoing for patients 12 years and older with late-onset OTC deficiency[2].

Potential Benefits

The main goals of this treatment are to:

  • Improve OTC function and maintain safe ammonia levels in the blood[2].
  • Reduce the occurrence of hyperammonemic crises (HACs), which are dangerous episodes of high ammonia levels[2].
  • Improve overall health outcomes for patients with OTC deficiency[2].

Safety Considerations

As with any new treatment, safety is a primary concern. The clinical trials are closely monitoring:

  • The incidence of adverse events (AEs) and serious adverse events (SAEs)[1].
  • Changes in laboratory values, physical examination results, and vital signs[2].
  • The development of antibodies against the OTC protein[2].

Who Is Eligible for This Treatment?

Based on the ongoing clinical trials, potential candidates for this treatment include:

  • Patients 12 years of age or older[2].
  • Those with a confirmed diagnosis of late-onset OTC deficiency[2].
  • Patients with a documented history of at least one symptomatic hyperammonemia episode[2].

However, there are several exclusion criteria, including liver transplant recipients, those with significant liver disease, and patients with certain active infections[2].

Future Prospects

Avalotcagene ontaparvovec represents a promising approach to treating OTC deficiency. If successful, it could offer a one-time treatment that addresses the root cause of the disease, potentially reducing or eliminating the need for current management strategies like ammonia scavenger therapy and protein-restricted diets[2].

As research continues, more information will become available about the long-term safety and efficacy of this innovative gene therapy. Patients with OTC deficiency and their families should stay informed about the progress of these clinical trials and discuss potential treatment options with their healthcare providers.

Aspect Details
Drug Name Avalotcagene Ontaparvovec (DTX301)
Condition Treated Late-onset Ornithine Transcarbamylase (OTC) Deficiency
Type of Therapy Gene therapy using adeno-associated virus serotype 8 (AAV8)
Administration Single intravenous infusion
Trial Phase Phase 3
Primary Objectives Evaluate efficacy in maintaining safe plasma ammonia levels and achieving complete response
Key Eligibility Criteria Age 12+, confirmed OTC deficiency diagnosis, history of hyperammonemia
Study Duration Up to 324 weeks (about 6 years) for long-term follow-up
Safety Monitoring Adverse events, laboratory values, physical examinations, vital signs

FAQ

  • What is Avalotcagene Ontaparvovec? Avalotcagene Ontaparvovec is a gene therapy that uses a modified virus to deliver a functional copy of the OTC gene to patients with late-onset OTC deficiency. It aims to improve the body's ability to process nitrogen and reduce ammonia levels in the blood.
  • How is Avalotcagene Ontaparvovec administered? The therapy is administered as a single, peripheral intravenous infusion. This means it's given through a vein in the arm or hand, typically in a medical setting.
  • Who is eligible for these clinical trials? The trials are primarily for patients aged 12 and older with a confirmed diagnosis of late-onset OTC deficiency. Participants must have a documented history of at least one symptomatic hyperammonemia episode and be currently receiving ammonia scavenger therapy and/or following a protein-restricted diet.
  • What are the main goals of these clinical trials? The primary goals are to evaluate the safety of Avalotcagene Ontaparvovec and its effectiveness in improving OTC function, maintaining safe ammonia levels in the blood, and reducing the occurrence of hyperammonemic crises.
  • How long do the clinical trials last? The trials include a screening period, a treatment period of 64 weeks, and a long-term follow-up period. The total duration can be up to 324 weeks (about 6 years) for some participants, allowing researchers to assess long-term safety and efficacy.

Ongoing Clinical Trials on Avalotcagene Ontaparvovec

  • Study of Avalotcagene Ontaparvovec for Patients Aged 12 and Older with Late-onset Ornithine Transcarbamylase Deficiency

    Not recruiting

    3 1 1
    Investigated drugs:
    France Germany Italy The Netherlands Portugal Spain

  • Long-Term Study on the Safety of Avalotcagene Ontaparvovec for Adults with Late-Onset Ornithine Transcarbamylase Deficiency

    Not recruiting

    1 1 1
    Investigated drugs:
    France Spain

Glossary

  • Ornithine Transcarbamylase (OTC) Deficiency: A rare genetic disorder that affects the body's ability to break down nitrogen, leading to potentially dangerous ammonia buildup in the blood.
  • Gene Therapy: A technique that uses genes to treat or prevent disease. In this case, a functional copy of the OTC gene is introduced into the patient's cells to help correct the genetic disorder.
  • Adeno-Associated Virus (AAV): A small virus that is not known to cause disease and is commonly used in gene therapy to deliver genetic material into cells.
  • Hyperammonemia: A condition characterized by high levels of ammonia in the blood, which can be toxic to the brain and other organs.
  • Ammonia Scavenger Therapy: Medications used to remove excess ammonia from the blood in patients with urea cycle disorders like OTC deficiency.
  • Protein-Restricted Diet: A diet that limits the intake of protein to help manage conditions like OTC deficiency by reducing the amount of nitrogen the body needs to process.
  • Ureagenesis: The process by which the body produces urea, a waste product that helps remove excess nitrogen from the body.
  • Placebo: An inactive substance that looks like the real medicine but has no therapeutic effect, used as a control in clinical trials.
  • AUC0-24: Area Under the Curve from 0 to 24 hours, a measure used to quantify the total exposure to a substance (in this case, ammonia) over a 24-hour period.

References

  1. http://clinicaltrials.eu/trial/long-term-study-on-the-safety-of-avalotcagene-ontaparvovec-for-adults-with-late-onset-ornithine-transcarbamylase-deficiency/
  2. http://clinicaltrials.eu/trial/study-of-avalotcagene-ontaparvovec-for-patients-aged-12-and-older-with-late-onset-ornithine-transcarbamylase-deficiency/