Orchard Therapeutics presents OTL-200 trial data at EBMT

Orchard Therapeutics presented the full registrational dataset from a 20 patient trial evaluating the efficacy and safety of OTL-200, an ex vivo autologous hematopoietic stem cell-based, or HSC, gene therapy for the treatment of metachromatic leukodystrophy, or MLD. The data, which included updated results on the two-year primary endpoints, in addition to new follow-up data at three years, were featured in an oral presentation at the European Society for Blood and Marrow Transplantation, or EBMT. For the co-primary endpoints evaluated at two years and then at three years after gene therapy, OTL-200 has shown a reconstitution of ARSA activity in the hematopoietic system was observed in all treated patients, with values within or above the normal reference range by 3 months post-treatment and remaining stable throughout the duration of the follow-up period. The trial also had a clinically meaningful treatment difference in gross motor function well above the pre-specified 10 percentage point threshold established in the trial. Stable engraftment of gene-corrected cells was observed in treated patients from one-month post-treatment, with persistent and stable vector copy number in CD34+ bone marrow cells and peripheral blood mononuclear cells throughout the follow-up period. At an age when patients in the untreated natural history cohort showed severe cognitive impairment, cognitive performance scores were maintained within normal range for most treated patients, independent of their symptomatic status at the time of treatment. Changes observed on brain MRIs of patients treated with OTL-200 suggest that OTL-200 may prevent, stabilize or markedly delay the progressive atrophy and demyelination typically observed with MLD. A greater effect was observed in early-onset MLD patients treated prior to the presentation of overt symptoms. Treatment with OTL-200 was well-tolerated and had a positive benefit-risk profile, with no adverse events or deaths related to treatment and no signs of genotoxicity. To date, no cases of malignancy or adverse events indicative of oncogenic transformation have been reported. There was no evidence of abnormal clonal proliferation as assessed by clinical and laboratory examination. The company intends to complete the necessary development work and prepare a marketing authorization application, or MAA, for submission in Europe in 2020. Work is also underway to prepare a biologics licensing application, or BLA, for submission in the U.S.

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