BOSTON and LONDON - Orchard Therapeutics (Nasdaq: ORTX), a global gene therapy leader, announced the publication in The Lancet of long-term clinical outcomes evaluating the safety and efficacy of Libmeldy (atidarsagene autotemcel) for the treatment of early-onset metachromatic leukodystrophy (MLD). Libmeldy is the only approved one-time gene therapy intended to correct the underlying cause of MLD for eligible patients in the European Union, UK, Iceland, Liechtenstein and Norway. Also known as OTL-200, it is an investigational therapy in the U.S.

'MLD is a cruel and ultimately fatal disease for which there were previously no approved treatment options beyond supportive care,' said Professor Alessandro Aiuti, deputy director of the San Raffaele Telethon Institute for Gene Therapy in Milan and full professor of pediatrics at the Vita-Salute San Raffaele University of Milan and a senior author of The Lancet manuscript. 'Libmeldy represents a significant step forward in the treatment of MLD. These data highlight the potential long-term benefits of HSC gene therapy for these children, especially when intervention prior to symptom onset is possible.'

Twenty-nine pediatric patients with early-onset MLD, enrolled in either a prospective non-randomized clinical study (n=20) or treated under expanded access frameworks (n=9), were administered Libmeldy and compared with an untreated natural history cohort of 31 patients adjusted for age and disease subtype. Most patients treated with Libmeldy developed motor skills within the predicted range of healthy children or maintained the ability to walk. Treatment with Libmeldy was well-tolerated and there was no evidence of abnormal clonal proliferation or replication-competent lentivirus over the follow up period. There were no treatment-related mortality or serious adverse events. Most adverse events were related to conditioning or background disease. Four patients developed transient anti-ARSA antibodies, which did not impact clinical outcomes.

'Treatment with Libmeldy resulted in sustained, clinically relevant benefits in children with early-onset MLD by preserving motor development and cognitive function in most patients,' said Bobby Gaspar, M.D., Ph.D., chief executive officer of Orchard Therapeutics. 'These are compelling results that underscore the potential of our HSC gene therapy approach to end the devastation caused by severe genetic diseases with a single treatment. We are commercializing Libmeldy in Europe and intend to pursue future potential regulatory approvals.'

Summary of Results Published in The Lancet

An integrated analysis was performed on data from 29 pediatric patients with a molecular and biochemical diagnosis of MLD and with either pre-symptomatic late-infantile (typically ranging from six to 30 months old at symptom onset) or pre- or early-symptomatic early juvenile (typically between 30 months and less than seven years old at symptom onset) disease and treated with Libmeldy in a prospective non-randomized clinical study or under expanded access frameworks. These included 16 (55%) pre-symptomatic late-infantile patients (one pre-symptomatic at enrollment became symptomatic by the time of treatment) and 13 (45%) early juvenile patients, eight of whom were early-symptomatic at the time of treatment. Patients were treated and monitored at Ospedale San Raffaele, Milan, Italy. Treated patients were compared with a historical cohort of 31 age- and disease subtype-matched MLD patients from a non-interventional natural history study.

At the time of analyses in 2018, results from all treated patients showed:

Efficacy Results

Total gross motor function measure (GMFM) scores were significantly improved in Libmeldy-treated patients compared to the natural history cohort at two years post-treatment (co-primary endpoint) for both late-infantile (66 percentage points [95% Confidence Interval (CI) 48.9-82.3], p

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