Clinical data | |
---|---|
Trade names | Libmeldy, Lenmeldy |
Other names | OTL-200 |
License data | |
Routes of administration | Intravenous infusion |
ATC code | |
Legal status | |
Legal status | |
Identifiers | |
UNII | |
KEGG |
Atidarsagene autotemcel, sold under the brand name Libmeldy among others, is a gene therapy treatment for metachromatic leukodystrophy developed by Orchard Therapeutics. It contains an autologous CD34⁺ cell enriched population that contains haematopoietic stem and progenitor cells transduced using a lentiviral vector encoding the human arylsulfatase A (ARSA) gene. [6]
The most common side effects include fever and low white blood cell count, mouth sores, respiratory infections, rash, medical line infections, viral infections, fever, gastrointestinal infections and enlarged liver. [7]
Atidarsagene autotemcel was approved for medical use in the European Union in December 2020, [4] [8] in the United Kingdom in February 2021, [1] and in the United States in March 2024. [7] Is it is the first gene therapy approved by the US Food and Drug Administration (FDA) for the treatment of metachromatic leukodystrophy. [7]
Atidarsagene autotemcel is indicated for the treatment of metachromatic leukodystrophy characterized by biallelic mutations in the arysulfatase A (ARSA) gene leading to a reduction of the ARSA enzymatic activity in children with late infantile or early juvenile forms, without clinical manifestations of the disease; and in children with the early juvenile form, with early clinical manifestations of the disease, who still have the ability to walk independently and before the onset of cognitive decline. [1] [4] [9]
In the US, atidarsagene autotemcel is indicated for the treatment of children with pre-symptomatic late infantile, pre-symptomatic early juvenile or early symptomatic early juvenile metachromatic leukodystrophy. [7]
Atidarsagene autotemcel is a one-time, individualized single-dose infusion made from the recipient's own hematopoietic (blood) stem cells, which have been genetically modified to include functional copies of the ARSA gene. [7] The stem cells are collected from the recipient and modified by adding a functional copy of the ARSA gene. [7] The modified stem cells are transplanted back into the recipient where they engraft (attach and multiply) within the bone marrow. [7] The modified stem cells supply the body with myeloid (immune) cells that produce the ARSA enzyme, which helps break down the harmful build-up of sulfatides and may stop the progression of MLD. [7] Prior to treatment, recipients must undergo high-dose chemotherapy, a process that removes cells from the bone marrow so they can be replaced with the modified cells in atidarsagene autotemcel. [7]
The FDA assessed the safety and effectiveness of atidarsagene autotemcel based on data from 37 children who received atidarsagene autotemcel in two single-arm, open-label clinical trials and in an expanded access program. [7] Children who received treatment with atidarsagene autotemcel were compared to untreated children (natural history). [7] The primary efficacy endpoint was severe motor impairment-free survival, defined as the interval from birth to the first occurrence of loss of locomotion and loss of sitting without support or death. [7] In children with metachromatic leukodystrophy, treatment with atidarsagene autotemcel significantly reduced the risk of severe motor impairment or death compared with untreated children. [7] All children with pre-symptomatic late infantile metachromatic leukodystrophy who were treated with atidarsagene autotemcel were alive at six years of age, compared to only 58% of children in the natural history group. [7] At five years of age, 71% of treated children were able to walk without assistance. [7] 85% of the children treated had normal language and performance IQ scores, which has not been reported in untreated children. [7] In addition, children with pre-symptomatic early juvenile and early symptomatic early juvenile metachromatic leukodystrophy showed slowing of motor and/or cognitive disease. [7]
The FDA granted the application for atidarsagene autotemcel priority review, orphan drug, rare pediatric disease, and regenerative medicine advanced therapy designations. [7] The FDA granted approval of Lenmeldy to Orchard Therapeutics. [7]
Atidarsagene autotemcel was approved for medical use in the EU in December 2020, [6] [4] in the UK in February 2021, [1] and the US in March 2024. [7] [10]
In February 2022, it was announced that NHS England would be providing the drug to metachromatic leukodystrophy patients, after negotiating a discount with the manufacturer. [11] [12] The assessment by BeneluxA concluded that it should only be reimbursed if the company offered a significant price reduction. [13] The National Centre for Pharmacoeconomics (NCPE) in Ireland recommends "that atidarsagene autotemcel not be considered for reimbursement unless cost effectiveness can be improved relative to existing treatment." [9]
Clinical data | |
---|---|
Trade names | Libmeldy, Lenmeldy |
Other names | OTL-200 |
License data | |
Routes of administration | Intravenous infusion |
ATC code | |
Legal status | |
Legal status | |
Identifiers | |
UNII | |
KEGG |
Atidarsagene autotemcel, sold under the brand name Libmeldy among others, is a gene therapy treatment for metachromatic leukodystrophy developed by Orchard Therapeutics. It contains an autologous CD34⁺ cell enriched population that contains haematopoietic stem and progenitor cells transduced using a lentiviral vector encoding the human arylsulfatase A (ARSA) gene. [6]
The most common side effects include fever and low white blood cell count, mouth sores, respiratory infections, rash, medical line infections, viral infections, fever, gastrointestinal infections and enlarged liver. [7]
Atidarsagene autotemcel was approved for medical use in the European Union in December 2020, [4] [8] in the United Kingdom in February 2021, [1] and in the United States in March 2024. [7] Is it is the first gene therapy approved by the US Food and Drug Administration (FDA) for the treatment of metachromatic leukodystrophy. [7]
Atidarsagene autotemcel is indicated for the treatment of metachromatic leukodystrophy characterized by biallelic mutations in the arysulfatase A (ARSA) gene leading to a reduction of the ARSA enzymatic activity in children with late infantile or early juvenile forms, without clinical manifestations of the disease; and in children with the early juvenile form, with early clinical manifestations of the disease, who still have the ability to walk independently and before the onset of cognitive decline. [1] [4] [9]
In the US, atidarsagene autotemcel is indicated for the treatment of children with pre-symptomatic late infantile, pre-symptomatic early juvenile or early symptomatic early juvenile metachromatic leukodystrophy. [7]
Atidarsagene autotemcel is a one-time, individualized single-dose infusion made from the recipient's own hematopoietic (blood) stem cells, which have been genetically modified to include functional copies of the ARSA gene. [7] The stem cells are collected from the recipient and modified by adding a functional copy of the ARSA gene. [7] The modified stem cells are transplanted back into the recipient where they engraft (attach and multiply) within the bone marrow. [7] The modified stem cells supply the body with myeloid (immune) cells that produce the ARSA enzyme, which helps break down the harmful build-up of sulfatides and may stop the progression of MLD. [7] Prior to treatment, recipients must undergo high-dose chemotherapy, a process that removes cells from the bone marrow so they can be replaced with the modified cells in atidarsagene autotemcel. [7]
The FDA assessed the safety and effectiveness of atidarsagene autotemcel based on data from 37 children who received atidarsagene autotemcel in two single-arm, open-label clinical trials and in an expanded access program. [7] Children who received treatment with atidarsagene autotemcel were compared to untreated children (natural history). [7] The primary efficacy endpoint was severe motor impairment-free survival, defined as the interval from birth to the first occurrence of loss of locomotion and loss of sitting without support or death. [7] In children with metachromatic leukodystrophy, treatment with atidarsagene autotemcel significantly reduced the risk of severe motor impairment or death compared with untreated children. [7] All children with pre-symptomatic late infantile metachromatic leukodystrophy who were treated with atidarsagene autotemcel were alive at six years of age, compared to only 58% of children in the natural history group. [7] At five years of age, 71% of treated children were able to walk without assistance. [7] 85% of the children treated had normal language and performance IQ scores, which has not been reported in untreated children. [7] In addition, children with pre-symptomatic early juvenile and early symptomatic early juvenile metachromatic leukodystrophy showed slowing of motor and/or cognitive disease. [7]
The FDA granted the application for atidarsagene autotemcel priority review, orphan drug, rare pediatric disease, and regenerative medicine advanced therapy designations. [7] The FDA granted approval of Lenmeldy to Orchard Therapeutics. [7]
Atidarsagene autotemcel was approved for medical use in the EU in December 2020, [6] [4] in the UK in February 2021, [1] and the US in March 2024. [7] [10]
In February 2022, it was announced that NHS England would be providing the drug to metachromatic leukodystrophy patients, after negotiating a discount with the manufacturer. [11] [12] The assessment by BeneluxA concluded that it should only be reimbursed if the company offered a significant price reduction. [13] The National Centre for Pharmacoeconomics (NCPE) in Ireland recommends "that atidarsagene autotemcel not be considered for reimbursement unless cost effectiveness can be improved relative to existing treatment." [9]