NAV

Eladocagene exuparvovec

Identification

Summary

Eladocagene exuparvovec is a recombinant AAV2 vector containing the human aromatic L-amino acid decarboxylase (AADC) gene indicated for the treatment of AADC deficiency.

Brand Names
Upstaza
Generic Name
Eladocagene exuparvovec
DrugBank Accession Number
DB16780
Background

Eladocagene exuparvovec is a recombinant adeno-associated virus-2 (AAV2)-based gene therapy that expresses human aromatic L-amino acid decarboxylase (AADC), and it is used to treat AADC deficiency, a fatal and rare genetic disorder that causes severe disability in pediatric patients.4,5 Patients with AADC have mutations in the dopa decarboxylase (DDC) gene that encodes the AADC enzyme. By promoting the expression of AADC, eladocagene exuparvovec leads to the development of motor function in patients with AADC deficiency. Eladocagene exuparvovec is infused directly into the brain (putamen) by bilateral intraputaminal infusion in one surgical session.4

Eladocagene exuparvovec received EMA approval in July 2022.3,5 Before the approval of this gene therapy, the treatment options for patients with AADC deficiency were limited to attempts to increase monoamine neurotransmitter production, decrease neurotransmitter catabolism via monoamine oxidase (MAO) inhibition and address symptoms.1

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Gene Therapies
Other gene therapies
Synonyms
  • Eladocagene exuparvovec
External IDs
  • AGIL-AADC
Poor quality drug data slowing you down?
Unlock 38% more drug discovery time and eliminate decision-making doubts with this one-stop guide to quality drug data.
Download eBook
Poor quality drug data slowing you down?
Download eBook

Pharmacology

Indication

Eladocagene exuparvovec is indicated for the treatment of patients aged 18 months and older with a clinical, molecular, and genetically confirmed diagnosis of aromatic L-amino acid decarboxylase (AADC) deficiency with a severe phenotype.4

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofAromatic l-amino acid decarboxylase (aadc) deficiency••••••••••••••••••••• ••••••••• •• •••• ••••••••••• •••••• ••••••••• •• •••• ••••••••••••••••••
Contraindications & Blackbox Warnings
Prevent Adverse Drug Events Today
Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events with our Clinical API
Learn more
Pharmacodynamics

The success and stability of aromatic L-amino acid decarboxylase (AADC) gene transduction achieved with eladocagene exuparvovec was evaluated by measuring L-6-[18F] fluoro-3, 4-dihydroxyphenylalanine (18F-DOPA) uptake. An increase in 18F-DOPA uptake was evident as early as 6 months after treatment, and was sustained for at least 5 years. The use of eladocagene exuparvovec led to motor milestones acquisition as early as 12 months after administration.4

In patients treated with eladocagene exuparvovec, dyskinesia or insomnia may occur or worsen 1 month after administration. Complications of eladocagene exuparvovec treatment, such as leakage of the fluid surrounding the brain, meningitis, or encephalitis, should be monitored.4

Mechanism of action

Eladocagene exuparvovec is a recombinant adeno-associated virus-2 (AAV2) vector that expresses human aromatic L-amino acid decarboxylase (AADC).4 It is used to treat patients with AADC deficiency, an autosomal recessive condition caused by mutations in the dopa decarboxylase (DDC) gene. The DDC gene encodes the AADC enzyme, which converts L-3,4-dihydroxyphenylalanine (L-DOPA) to dopamine and 5-hydroxytryptophan to serotonin.2 However, the mutations present in patients with AADC deficiency lead to the reduction or absence of AADC enzyme activity, causing a depletion in neurotransmitter levels and a failure to achieve developmental milestones.

Eladocagene exuparvovec is administered to the putamen of patients with AADC deficiency (direct brain infusion), where it drives the production of the AADC enzyme and increases dopamine levels. Consequently, the use of eladocagene exuparvovec improves the development of motor function in treated patients with AADC deficiency.1,4

Absorption

Pharmacokinetic studies with eladocagene exuparvovec have not been performed. Eladocagene exuparvovec is infused directly into the brain and has not been shown to distribute outside the CNS.4

Volume of distribution

The biodistribution of eladocagene exuparvovec was evaluated using a real-time polymerase chain reaction assay. Eladocagene exuparvovec was not detected in blood and urine at baseline or 12 months after treatment.4

Protein binding

Not available.

Metabolism

As a gene therapy product, eladocagene exuparvovec is expected to be metabolized by nucleases throughout the body.

Route of elimination

Not available.

Half-life

Not available.

Clearance

Not available.

Adverse Effects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!
See the data
Improve decision support & research outcomes with our structured adverse effects data.
See a data sample
Toxicity

There is no clinical experience with overdose of eladocagene exuparvovec. In case of overdose, the EMA label advises that symptomatic and supportive treatment, as deemed necessary by the treating physician, is provided. Close clinical observation and monitoring of laboratory parameters for systemic immune response are recommended. Accidental exposure to eladocagene exuparvovec, including contact with skin, eyes, and mucous membranes, is to be avoided.4

In vivo studies evaluating the carcinogenic or mutagenic effects of eladocagene exuparvovec have not been performed. No toxicological effects in male or female reproductive organs were detected in animal studies. In rats, no evidence of viral shedding outside of the central nervous system was observed, except for cerebrospinal fluid seven days after eladocagene exuparvovec administration.4

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
Not Available

Products

Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
International/Other Brands
Upstaza (PTC Therapeutics)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
UpstazaInjection, solution560000000000 vg/mlPtc Therapeutics2022-08-16Not applicableEU flag

Categories

Drug Categories
Classification
Not classified
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
S51J6N56M7
CAS number
2098615-91-7

References

General References
  1. Tai CH, Lee NC, Chien YH, Byrne BJ, Muramatsu SI, Tseng SH, Hwu WL: Long-term efficacy and safety of eladocagene exuparvovec in patients with AADC deficiency. Mol Ther. 2022 Feb 2;30(2):509-518. doi: 10.1016/j.ymthe.2021.11.005. Epub 2021 Nov 8. [Article]
  2. Kojima K, Nakajima T, Taga N, Miyauchi A, Kato M, Matsumoto A, Ikeda T, Nakamura K, Kubota T, Mizukami H, Ono S, Onuki Y, Sato T, Osaka H, Muramatsu SI, Yamagata T: Gene therapy improves motor and mental function of aromatic l-amino acid decarboxylase deficiency. Brain. 2019 Feb 1;142(2):322-333. doi: 10.1093/brain/awy331. [Article]
  3. Keam SJ: Eladocagene Exuparvovec: First Approval. Drugs. 2022 Sep;82(13):1427-1432. doi: 10.1007/s40265-022-01775-3. [Article]
  4. EMA Assessment Report: Upstaza (eladocagene exuparvovec) solution for infusion [Link]
  5. PTC Therapeutics: Upstaza Granted Marketing Authorization by European Commission as First Disease-Modifying Treatment for AADC Deficiency [Link]
Wikipedia
Eladocagene_exuparvovec

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1, 2CompletedTreatmentAromatic L-amino Acid Decarboxylase (AADC) Deficiency1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, solution560000000000 vg/ml
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
Not Available

Drug created at May 10, 2022 18:20 / Updated at December 01, 2022 11:30