- First gene therapy infused directly into the brain for the treatment of AADC deficiency
- MHRA authorisation follows recent European Union authorisation
- AADC deficiency is a rare, fatal disorder that arrests motor development causing severe disability
PTC Therapeutics, Inc. announced on 17th November that Upstaza™ (eladocagene exuparvovec) was granted authorisation by the Medicines and Healthcare Products Regulatory Agency (MHRA) in Great Britain. Upstaza is the first and only approved disease-modifying treatment for aromatic L-amino acid decarboxylase (AADC) deficiency and the first marketed gene therapy directly infused into the brain. It is approved for patients 18 months and older.
“We are thrilled with the MHRA’s rapid authorisation of Upstaza,” said Stuart W. Peltz, Ph.D., Chief Executive Officer, PTC Therapeutics. “Patients in the UK with AADC deficiency are one step closer to having access to a much-needed disease modifying therapy. This is another milestone towards our commitment to advance innovative treatments and improve outcomes for people living with rare diseases.”
During Upstaza clinical studies, patients went from not achieving any developmental motor milestones to demonstrating a mastery of clinically meaningful motor skills, including the ability to ambulate independently. Milestone achievements including cognitive and language acquisition occurred from as early as three months following treatment, with clinically significant improvements shown to continue up to ten years after treatment. Upstaza also reduced symptoms that cause potentially life-threatening and morbid complications.
“The approval of an AADC deficiency gene therapy in the UK will provide the opportunity to transform the prognosis for those born and living with this disease, and we are hopeful for access in the coming months. Without treatment, most children born with AADC deficiency will have difficulty with their development and many of the symptoms can be distressing and life-threatening. The impact on those living with AADC and their communities is significant, with children facing frequent hospitalisations, emergency visits and requiring a multi-disciplinary team of highly trained specialists,” stated Kirsty Hoyle, CEO, Metabolic Support UK.
Upstaza has marketing authorisation in all 27 European Union member states, as well as Iceland, Norway, Liechtenstein, and Northern Ireland.
- Tai CH, et al. Long-term efficacy and safety of eladocagene exuparvovec in patients with AADC deficiency. Mol Ther. 2022;30(2):509-518.
- Chien et al. AGIL-AADC gene therapy results in sustained improvements in motor and developmental milestones through 5 years in children with AADC deficiency. Poster presented at the 48th Annual Meeting of the Child Neurology Society, Charlotte, NC, USA, Oct 23-26, 2019.
- Chien YH, et al. Efficacy and safety of AAV2 gene therapy in children with aromatic L-amino acid decarboxylase deficiency: an open-label, phase 1/2 trial. Lancet
About Upstaza™ (eladocagene exuparvovec)
Upstaza is a one-time gene replacement therapy indicated for the treatment of patients aged 18 months and older with a clinical, molecular, and genetically confirmed diagnosis of aromatic L‑amino acid decarboxylase (AADC) deficiency with a severe phenotype. It is a recombinant adeno-associated virus serotype 2 (AAV2)-based gene therapy, containing the human DDC gene.1 It is designed to correct the underlying genetic defect, by delivering a functioning DDC gene directly into the putamen, increasing the AADC enzyme and restoring dopamine production.2,3
The efficacy and safety profile of Upstaza has been demonstrated across clinical trials and compassionate use programmes.1 The first patient was dosed in 2010. In clinical trials, Upstaza demonstrated transformational neurological improvements. The most common side effects were initial insomnia, irritability and dyskinesia.
Administration of Upstaza occurs through a stereotactic surgical procedure, a minimally invasive neurosurgical procedure used for the treatment of a number of paediatric and adult neurological disorders. The Upstaza administration procedure is performed by a qualified neurosurgeon in centers specialised in stereotactic neurosurgery.
About aromatic L-amino acid decarboxylase (AADC) deficiency
AADC deficiency is a fatal, rare genetic disorder that typically causes severe disability and suffering from the first months of life, affecting every aspect of life – physical, mental and behavioural. The suffering of children with AADC deficiency may be exacerbated by: episodes of distressing seizure-like oculogyric crises causing the eyes to roll up in the head, frequent vomiting, behavioural problems, and difficulty sleeping.
The lives of affected children are severely impacted and shortened. Ongoing physical, occupational and speech therapy, and interventions, including surgery, also are often required to manage potentially life-threatening complications such as infections, severe feeding and breathing problems.
About PTC Therapeutics, Inc.
PTC is a science-driven, global biopharmaceutical company focused on the discovery, development and commercialization of clinically differentiated medicines that provide benefits to patients with rare disorders. PTC’s ability to innovate to identify new therapies and to globally commercialise products is the foundation that drives investment in a robust and diversified pipeline of transformative medicines. PTC’s mission is to provide access to best-in-class treatments for patients who have little to no treatment options.