Leriglitazone is being developed for the treatment of X-linked adrenoleukodystrophy (ALD) which presents with two main phenotypes: adrenomyeloneuropathy (AMN) and cerebral ALD (cALD). ALD is an inherited disease in which there is a build-up of fatty substances known as ‘very long chain fatty acids’ (VLCFAs) in tissues around the body, mainly in the brain and spinal cord and in the adrenal glands. The condition, which affects mostly males, is caused by abnormalities in a gene called ABCD1 which is responsible for the production of the protein needed to break down VLCFAs and prevent them from accumulating in tissues. Symptoms of the condition include behavioural problems, problems with vision, hearing and coordination, seizures (fits) and dementia. ALD is a life-threatening and long-term debilitating condition due to the progressive damage to the brain and nerves.
Leriglitazone is expected to work in patients with ALD by activating receptors called ‘PPAR gamma’, found in the mitochondria, which are components within cells that generate energy. Leriglitazone will improve the ALD pathogenic cascade by improving mitochondrial dysfunction, reducing oxidative stress and neuroinflammation, promoting demyelination and halting axonal degeneration. Hence, leriglitazone is expected to protect cells from damage and slow the progression of the disease. If licensed, leriglitazone would offer the first drug treatment option for adult ALD patients with AMN who currently have no effective therapies available.
Pegunigalsidase alfa is produced by a method known as ‘recombinant DNA technology’: it is made by cells into which a gene (DNA) has been introduced, which makes them able to produce the enzyme. The replacement enzyme has also been modified to reduce the rate at which it is removed from the body, allowing it to act for longer. Pegunigalsidase alfa was designed to increase amount of medicine in the blood and reduce the ability of a substance to provoke an immune response, thereby enhancing efficacy compared with available products. If licensed, pegunigalsidase alfa would offer an additional first-line, long -term ERT options for adult and paediatric patients (>3 yr) diagnosed with FD.