The main objective of MIN4ALD is to assess leriglitazone as a treatment for paediatric cerebral adrenoleukodystrophy (cALD) and bring it closer to the market. Leriglitazone is new brain penetrant, full and selective peroxisome proliferator-activated receptor γ agonist. Thanks to its adequate blood-brain barrier penetration and good bioavailability, leriglitazone acts as a disease-modifying therapy reaching adequate central nervous system (CNS) exposure to modulate multiple biological pathways relevant to clinical manifestations of adrenoleukodystrophy (ALD) and potentially in other CNS diseases.
Childhood cALD is a rapidly progressing and devastating disease that occurs in 31-35% of ALD patients with onset typically between age 2 and 12 years of age. The rate at which cALD progresses may vary but is characterized individuals experiencing learning and behavioural difficulties, aggressive behaviour, swallowing difficulties, vision problems, poor coordination, and eventually leading to a vegetative state or death after 2-4 years from disease onset.
There is no pharmacological treatment approved for patients with ALD. If childhood cALD is detected in the early stages patients may undergo Hematopoietic Stem Cell Transplantation (HSCT) to arrest the inflammatory demyelination. The procedure is, however, associated with serious and sometimes fatal complications for the patients, and require finding compatible donors. Since HSCT needs to be performed in early stages of the disease, and requires finding appropriate donors, this option is only available for a portion of paediatric cALD patients. A treatment that would halt or decelerate lesion progression would be extremely beneficial either to avoid the need of HSCT and/or to provide the required time for finding a suitable donor.
Leriglitazone demonstrated strong preclinical proof-of-concept in relevant animal models of CNS diseases related with cALD (neurodegeneration and neuroinflammation). In Phase I studies and a Phase II/III study in adult male ALD patients, leriglitazone showed a favourable benefit-risk profile, with a reduction in myelopathy progression and notably, a reduction of cerebral lesion progression leading to cALD. Only patients on placebo developed cALD during the study. Of importance, leriglitazone showed to be generally well tolerated. At the moment, the marketing authorization application (MAA) and launch preparations for male ALD patients in the EU are underway.
Therefore, the achievement of the current project on paediatric patients would be of great importance as it would allow extending the use of leriglitazone into a patient population with a highly unmet medical need. This is also an outstanding business opportunity that will place the company in a global leading position in the orphan space. The development of better treatment options is a health challenge, with a paramount social impact not only for the orphan diseases community, but for the whole society.
