PTC gets green light for gene therapy Upstaza in EU

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PTC Therapeutic's Upstaza  gene therapy for patients with genetic disorder AADC deficiency has been recommended for approval in the EU, setting up another test of the commercial prospects for gene therapies in the bloc.

Once full approval is granted Upstaza (eladocagene exuparvovec) will become the first disease-modifying treatment for AADC (aromatic L-amino acid decarboxylase) deficiency, as well as the first gene therapy directly administered into the brain, said PTC.

AADC deficiency is a fatal rare disorder that causes severe disability and suffering from the first months of life, with children afflicted by the condition suffering physical, mental and behavioural symptoms, including seizures.

With the EMA's CHMP human medicines committee concluding that Upstaza is an effective treatment for children with the disorder, the big question is whether PTC can build a commercially viable business for the therapy in Europe, something that has eluded other developers.

UniQure's Glybera for lipoprotein lipase deficiency was approved a decade ago, but was pulled off the market a few years later on low demand and questions about its effectiveness.

Orchard Therapeutics' Strimvelis for the vanishingly rare "bubble boy" disease adenosine deaminase deficiency (ADA-SCID) – originally developed by GlaxoSmithKline – reached the market in 2016, but is still only available through a single clinic in Italy and is used in too few patients to cover its costs.

The company is generating better traction, however, with Libmeldy for children with metachromatic leukodystrophy (MLD), and has secured reimbursement approvals in Italy, as well as the UK.

Most tellingly, bluebird bio said last year it would exit the European market altogether, saying it was "untenable" to bring gene therapies to market there after failing to reach a pricing agreement with Germany for its beta thalassaemia treatment Zynteglo.

There's no word on pricing for Upstaza yet, although the one-shot therapy is likely to cost in the millions of euros in common with other approved gene therapies such as Novartis' Zolgensma for spinal muscular atrophy at around €2 million. PTC is holding a conference call later today to discuss the CHMP recommendation.

Currently, there are no approved therapies for the treatment of AADC deficiency, and the CHMP backed Upstaza "under exceptional circumstances" on the strength of data generated mainly in Taiwan on unblinded studies involving 28 children aged between 18 months and eight years.