Gene Therapy Candidate Gets Priority Review for Metachromatic Leukodystrophy

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OTL-200 is an ex vivo autologous hematopoietic stem cell gene therapy.

The Food and Drug Administration (FDA) has accepted for Priority Review the Biologics License Application (BLA) for OTL-200 (atidarsagene autotemcel) for the treatment of metachromatic leukodystrophy, a rare inherited lysosomal storage disease.

Metachromatic leukodystrophy (MLD) is caused by a mutation in the arylsulfatase-A (ARSA) gene that results in a buildup of sulfatides in the brain and other areas of the body, including the liver, gallbladder, kidneys, and/or spleen. OTL-200 is an investigational hematopoietic stem cell-based gene therapy. 

The BLA is supported by data from 39 pediatric patients with early-onset MLD treated with OTL-200 who were enrolled in 2 prospective, nonrandomized clinical studies (n=30) or treated under expanded access frameworks (n=9). Study participants were compared with natural history data from 49 untreated patients. 

The composite 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 (Gross Motor Function Classification-MLD [GMFC-MLD] Level ≥ 5) or death.

At the time of the updated integrated analysis (median follow-up of 6.76 years, range 0.64-12.19 years), results showed that 17 out of 18 presymptomatic late infantile patients maintained the ability to walk at last assessment (GMFC-MLD Level 2 or better) vs untreated late infantile natural history patients, all of whom lost all locomotion (GMFC-MLD Level 5 or worse) by a median age of 2.6 years (P <.001).

Additionally, all 7 surviving presymptomatic early juvenile patients maintained the ability to walk without support with quality and performance normal for age at last assessment (GMFC-MLD Level 0) (P =.042), and 7 out of 9 surviving early-symptomatic early juvenile patients maintained the ability to sit without support and/or crawl/roll at last assessment (GMFC-MLD Level 4 or better) (P <.001) vs untreated early juvenile natural history patients, all of whom lost all locomotion (GMFC-MLD Level 5 or worse) by a median age of 6.4 years.

As for safety, OTL-200 was well tolerated with no treatment-related serious adverse events or deaths reported.

A Prescription Drug User Fee Act target date of March 18, 2024 has been set for the application. “Due to the nature of the disease and the urgency to treat children affected by MLD, we are working diligently in parallel to prepare for a potential launch in 2024 and ensure OTL-200 will be available to patients in the US as quickly as possible,” said Bobby Gaspar, MD, PhD, co-founder and chief executive officer of Orchard Therapeutics.


  1. Orchard Therapeutics announces acceptance of Biologics License Application for OTL-200 in MLD and receives Priority Review. News release. Orchard Therapeutics. September 18, 2023.
  2. Orchard Therapeutics announces presentation of data comprising the clinical package for the OTL-200 BLA in MLD at the SSIEM Annual Symposium 2023. News release. Orchard Therapeutics. August 31, 2023. Accessed September 18, 2023.