General Information

Lenmeldy (atidarsagene autotemcel) is an autologous hematopoietic stem cell-based gene therapy.

Lenmeldy is specifically  indicated for the treatment of children with pre-symptomatic late infantile (PSLI), pre-symptomatic early juvenile (PSEJ) or early symptomatic early juvenile (ESEJ) metachromatic leukodystrophy (MLD).

Dosing/Administration

Lenmeldy is for autologous use only as a one-time single-dose intravenous administration.

Children are required to undergo hematopoietic stem cell (HSC) mobilization followed by apheresis to obtain CD34+ cells for Lenmeldy manufacturing. 

 Dosing of Lenmeldy is based on the number of CD34+ cells in the infusion bag(s) per kg of body weight. 

 Myeloablative conditioning must be administered before infusion of Lenmeldy. 

Confirm that the child’s identity matches the unique patient identification information on the Lenmeldy infusion bag(s) prior to infusion. 

Do not sample, alter, irradiate, or refreeze Lenmeldy . Do not use a leukodepleting filter.

Minimum and Maximum Recommended Dose of Lenmeldy

Mechanism of Action

Lenmeldy (atidarsagene autotemcel) inserts one or more functional copies of the human ARSA complementary deoxyribonucleic acid (cDNA) into the patients’ HSCs, through transduction of autologous CD34+ cells with ARSA LVV. After Lenmeldy infusion, transduced CD34+ HSCs engraft in bone marrow, repopulate the hematopoietic compartment and their progeny produce ARSA enzyme. Functional ARSA enzyme can breakdown or prevent the harmful accumulation of sulfatides.

Side Effects

Adverse effects associated with the use of Lenmeldy may include, but are not limited to, the following:

• febrile neutropenia
• stomatitis
• respiratory tract infections
• rash
• device related infections
• other viral infections
• pyrexia
• gastroenteritis
• hepatomegaly
• laboratory abnormalities: elevated D-dimer (67%), neutropenia (28%), and elevated liver enzymes

Clinical Trial Results

FDA approval of Lenmeldy was based on data from 37 pediatric patients with early-onset MLD, enrolled in two single-arm, open-label clinical studies or treated under European expanded access frameworks, who received a one-time administration of the gene therapy and compared with natural history data. All treated patients were administered Lenmeldy and subsequently monitored at Ospedale San Raffaele in Milan, Italy.

With more than 12 years of follow-up in the earliest treated patients (median 6.76 years), treatment with Lenmeldy significantly extended overall survival and resulted in the preservation of motor function and cognitive skills in most late infantile MLD patients past ages at which untreated patients showed severe cognitive and motor impairments. Lenmeldy also resulted in the preservation of motor function and cognitive skills in some early juvenile MLD patients which is not expected when compared to untreated patients.