Manchester researchers contribute to landmark FDA approval for Hunter syndrome therapy 

In a major step forward for children with Hunter syndrome, also known as mucopolysaccharidosis type II (MPS II), the US Food and Drug Administration (FDA) has approved a new treatment that could significantly change how the condition is managed.  

The trials delivered at Royal Manchester Children’s Hospital (RMCH) in collaboration with the Manchester Centre for Genomic Medicine at Saint Mary’s Hospital – both part of Manchester University NHS Foundation Trust (MFT), played an important role in its approval as the only UK site leading early phase 1 and 2 clinical trials, and one of two sites outside North America. 

In March 2026, the FDA granted accelerated approval for a medicine called AVLAYAH™ (Tividenofusp alfa-eknm), an enzyme replacement therapy developed by Denali Therapeutics. It is the first treatment designed to help with the serious effects of Hunter syndrome on the brain, and it represents the biggest advance for this condition in almost 20 years. 

Children with Hunter syndrome, a rare, inherited condition, have an error in a gene, meaning they cannot produce an important enzyme that breaks down complex sugar molecules. Over time these sugars build up in organs and tissues, leading to joint stiffness, hearing loss, breathing and heart problems, developmental delays and cognitive decline. Children with Hunter syndrome experience severe neurological symptoms, with life expectancy typically between 10 and 20 years. 

Until now, available treatments could help with some physical symptoms but could not reach the brain. This meant that families had few options when it came to treating neurological symptoms of the disease. 

In Manchester, trials took place within the National Institute for Health and Care Research (NIHR) Manchester Clinical Research Facility (CRF) at RMCH, recruiting a small number of UK children to the study, known as DNLI‑E‑0002. 

All children recruited at the Willink Metabolic Unit at Manchester Centre for Genomic Medicine, received the drug, which works by replacing an enzyme missing in the body, as an investigational treatment from the beginning of the trial. 

The trial monitored the reduction of a complex sugar molecule ‘cerebrospinal fluid heparan sulfate’ that accumulates in the brain of children with Hunter syndrome and causes severe neurological decline. 

93% of children in the trial saw this reduce to normal levels (seen in unaffected children).  Improvements in areas such as cognitive development, behaviour and hearing were also reported. 

Margretha Amegadzie, Senior Paediatric Clinical Research Nurse at the NIHR Manchester CRF at RMCH, said: 

For families affected by Hunter syndrome, including the children we care for across our hospitals, this FDA approval is very reassuring. It gives renewed hope that future treatments will not only support physical health but could also help protect children’s learning and development.

Researchers at the Manchester Centre for Genomic Medicine contributed important early data on how safe the treatment is, how well it is tolerated, and how it works in children with Hunter syndrome.  

This information was included in the evidence reviewed by the FDA when deciding to approve AVLAYAH. While the decision was based on data from children around the world, the contribution from MFT helped strengthen the case that the treatment has the potential to offer real clinical benefit. 

Dr Daniela Castillo-Garcia, Clinical Research Fellow in Paediatric Inherited Metabolic disease at the Manchester Centre for Genomic Medicine, said: 

This is the first time in almost 20 years that a new treatment for this condition has been approved, and it marks an important step forward for families. We are incredibly proud to have contributed to this milestone through research carried out here in Manchester. 

“In the next phase of the trial, children will continue to receive the treatment as part of a long‑term extension study, which will focus on understanding how safe and effective the therapy remains over time. The trial design of the next phase is also expected to reduce the burden on families, with fewer invasive tests and the potential for more treatment to be delivered closer to home.” 

Professor Simon Jones and Dr Arunabha Ghosh, Consultants in Paediatric Inherited Metabolic Disease, have been the PIs for the study. 

AVLAYAH is now available in the United States.