Leriglitazone halts disease progression in adult patients with early cerebral adrenoleukodystrophy in compassionate-use study published in Brain

In a French early-access program study, 10 of 13 patients were clinically and radiologically stable

Mataró, Barcelona, Spain, 11 June, 2024 - Minoryx Therapeutics (“Minoryx”), a late-stage biotech company focused on the development of therapies for orphan central nervous system (CNS) disorders, today announce that results from a compassionate use study of leriglitazone for treatment of progressive cerebral adrenoleukodystrophy (cALD) in adult male patients, published in the peer-reviewed journal Brain.

The compassionate-use study was led by Fanny Mochel, MD, Ph.D., professor at the Hôpital Universitaire La Pitié-Salpêtrière (Paris, France), as part of an early-access program through the French national drug agency (ANSM) that allows for the use of innovative treatments with favorable safety profiles under a Compassionate Access Authorization protocol (ATU).

The publication describes 13 adult male patients with progressive cALD, a fatal neurodegenerative disorder that is characterized by growing, demyelinating brain lesions. The patients were either awaiting hematopoietic stem cell transplantation (HSCT) - the only treatment option for progressive cALD today - or ineligible for HSCT.

Among the 13 patients treated with leriglitazone, the disease stabilized clinically and in radiological tests in 10 patients through up to two years of follow-up. Five patients that had originally presented with gadolinium enhancement (active neuroinflammation) lesions in the corticospinal tract that usually lead to poor HSCT outcomes all became gadolinium negative. Importantly, the lesion load was reduced in four of these patients. Moreover, plasma neurofilament light chain levels (a biomarker for neurodegeneration) stabilized in all 10 patients and correlated with lesion load. The two patients who continued to deteriorate were both over 60 years of age with prominent cognitive impairment at baseline, while one patient died from Covid-19 a few months after initiating treatment. Leriglitazone was well tolerated in all patients, with minimal weight gain in most patients and moderate leg edema in only two patients.

These results are in contrast with the natural history for patients with progressive cALD, which predicts rapid lesion progression leading to acute neurological decline, with death occurring typically within 3-4 years of onset.

“This cohort study shows that leriglitazone can halt neuroinflammation and disease progression in adult patients with cALD at early disease stages, as evidenced by clinical, radiological, and biological stability for up to two years of treatment,” said Prof. Mochel. “All five patients who initiated treatment while on the waiting list for stem cell transplant have now been taken off, on the basis of the positive results observed with leriglitazone.”

“The results are very encouraging and support the efficacy of leriglitazone that we have observed in our clinical trials, ADVANCE3 and NEXUS4,” said Marc Martinell, CEO, Minoryx.“In these studies in adult and pediatric patients with cALD, leriglitazone is able to reduce further lesion development and stabilize patients clinically and radiologically. These results from Hôpital Universitaire La Pitié-Salpêtrière further confirm the effect of leriglitazone.”

In consultation and alignment with the U.S. Food and Drug Administration, Minoryx has launched a phase 3 clinical trial (CALYX5) in patients with adult progressive cALD that have a profile similar to those treated at Hôpital Universitaire La Pitié-Salpêtrière. CALYX is currently recruiting adult patients with progressive cALD in the U.S., Brazil, and Argentina.

Brain has provided a video summary of the study on their video channel.

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