The European Commission (EC) has granted marketing authorisation under exceptional circumstances for Nezglyal (leriglitazone), an orally bioavailable, brain penetrating, selective PPAR gamma agonist, as a treatment for male cALD patients. 

It is approved in patients aged two to 12 years with Gadolinium (Gd)-negative brain lesions and is the first approved pharmacological treatment for cALD in the European Union (EU).  

The approval is based on results from the Phase II/III NEXUS1 study and additional real-world evidence from compassionate use programmes. 

The first European launch is expected in Germany by the end of the year, with additional launches in Europe anticipated pending completion of national reimbursement negotiations. Developer Neuraxpharm is also evaluating appropriate access pathways for eligible patients. 

Cerebral adrenoleukodystrophy (cALD) is a debilitating neurodegenerative disease characterised by demyelinating brain lesions that can progress rapidly, leading to acute neurological decline and death in three to four years. 

“With childhood cALD, neurodegeneration is irreversible, so it is critical to halt disease progression early, ideally, before symptoms surface and signs of neuroinflammation appear. Until now, there were no pharmacological treatment options for early intervention. Invasive procedures, such as hematopoietic stem cell transplantation, are available for more progressed patients. However, they are donor-dependent and can only be applied within a very narrow time window,” said Dr Caroline Sevin, CRMR LeukoFrance, Hôpital du Kremlin Bicêtre, France: “That we now have a pharmacological treatment for early intervention is a major advance in our treatment of cALD.” 

Treatments to slow neurodegeneration 

Minoryx and Neuraxpharm entered into a license agreement under which Neuraxpharm will commercialise the product in Europe following marketing authorisation. 

Enrolment is now completed in the CALYX2 Phase III trial in adult male cALD patients with Gd-enhancing lesions, and the ongoing TREE3 Phase IIa trial in paediatric patients with Rett syndrome. 

“cALD is a rapidly progressing neurodegenerative disease which severely impacts the lives of patients and their families, underlining the critical need for treatments which can halt or slow disease progression and improve quality of life,” said Dr Jörg Thomas Dierks, CEO of Neuraxpharm. “Today’s announcement reinforces our commitment at Neuraxpharm to advancing innovative medicines that target CNS diseases with significant unmet clinical need. We’re looking forward to working with the local authorities, and the medical and patient communities to bring Nezglyal to eligible individuals across the region as quickly as possible.”