Results for Cryopreserved Gene Therapy Formulation for Treatment of Early-Onset Metachromatic Leukodystrophy

  • Cerebral adrenoleukodystrophy
  • Child neurology
  • Gene therapy

In initial results from the A Safety and Efficacy Study of Cryopreserved OTL-200 for Treatment of Metachromatic Leukodystrophy  (NCT03392987) of a cryopreserved gene therapy formulation (OTL-200: Orchard Therapeutics, Boston, MA) for the treatment of early-onset metachromatic leukodystrophy (MLD). 

Of the 4 participants with early-onset MLD, 2 with late-infantile and 2 with early-juvenile types, have been treated with the cryopreserved gene therapy. All participants are alive and were followed for a minimum of 1 month, with longest follow up of 12 months in the first participant treated (median follow up of 0.38 years). 

The initial results in participants who received the cryopreserved gene therapy include: 

  • Engraftment of gene-corrected 1 month after treatment remained stable throughout the length of follow up for all. 
  • Reconstitution of arylsulfatase-A (ARSA) enzyme activity consistent with results seen in those treated with the fresh formulation at the same time points. 
  • No treatment-related adverse events or signs of oncogenic transformation have been reported in the participants receiving the cryopreserved formulation to date. 
  • At the 12-month assessment, a participant surpassed the expected age of disease onset (15 months) based on an older untreated sibling, while attaining age-appropriate motor development. 

“Presenting the first supportive data on OTL-200 using a cryopreserved formulation represents a cross-functional effort involving our clinical, CMC and regulatory teams as we prepare for the upcoming European regulatory submission for MLD followed by a biologics licesnse application (BLA) in the US,” said Mark Rothera, president and chief executive officer of Orchard. “If approved, a cryopreserved formulation of OTL-200 would more readily facilitate global commercialization and patient access efforts, which are key elements in our mission to deliver potentially curative therapies to patients suffering from often-deadly rare diseases.” 

Mr. Rothera continued, “With over 40 patients now treated using a cryopreserved formulation across our pipeline of 6 clinical-stage programs, we are confident our approach is supported by a robust set of evidence.” 

“We are pleased that these initial data suggest that using gene-corrected cells that have been cryopreserved has a similar impact on clinical biomarkers for early-onset MLD patients as the OTL-200 fresh formulation,” said Dr. Valeria Calbi, a hematologist at San Raffaele Scientific Institute and SR-Tiget and an investigator of the study.

“The 4 treated patients showed good levels of engraftment of gene-corrected cells and reconstitution of ARSA activity at multiple time points, as well as encouraging early trends in the Gross Motor Function Measure (GMFM) scores that we look forward to evaluating with additional follow-up. We believe that these data further support the positive benefit / risk profile of OTL-200 as a therapy with potential lifelong benefit for patients with MLD.” 

Orchard remains on track to submit a marketing authorization application (MAA) in Europe for MLD in the first half of 2020, as well as a BLA in the US approximately 1 year later. 

The data are being featured this week in a poster session at the European Society of Gene & Cell Therapy (ESGCT) Annual Congress in Barcelona, Spain. 

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