Minoryx Therapeutics and Neuraxpharm have announced positive results from the NEXUS trial, indicating that leriglitazone, an investigational therapy, can slow the progression of cerebral adrenoleukodystrophy (cALD) in children. This outcome paves the way for the companies to refile for EU approval of leriglitazone for both pediatric and adult cALD patients, potentially offering a new treatment avenue for this devastating neurodegenerative disorder.
cALD is characterized by inflammation-driven demyelinating brain lesions that lead to rapid neurological decline and death within a few years. Currently, hematopoietic stem cell transplant (HSCT) is the standard of care in Europe, but many patients are ineligible for this procedure. Leriglitazone, a PPAR-gamma agonist, modulates inflammation, myelination, and mitochondrial function, addressing key pathways involved in cALD progression.
The NEXUS trial evaluated leriglitazone in 20 patients for at least 24 weeks. The results showed a statistically significant difference in the proportion of patients with clinical and radiological arrested disease after 96 weeks or prior to HSCT. Specifically, 35% of patients treated with leriglitazone met the criteria for arrested disease, compared to an expected rate of approximately 10% without treatment, according to Minoryx and Neuraxpharm.
"The NEXUS results attest that leriglitazone addresses a critical unmet need for non-invasive treatments that can be administered at the moment brain lesions are identified to arrest or slow down lesion growth," commented lead investigator Patricia Musolino, of Harvard Medical School.
Minoryx CEO Marc Martinell explained that leriglitazone's mechanism of action targets the inflammation and demyelination processes central to cALD pathology. In a previous clinical trial with adult patients, only those on placebo continued to develop progressive brain lesions. Interim data in pediatric patients also showed slower brain lesion progression compared to the natural history of untreated patients.
The company's initial application for leriglitazone (under the brand name Nezglyal) was previously rejected by the EMA. However, with the new data from the NEXUS trial, Minoryx and Neuraxpharm plan to resubmit their application for EU approval in mid-2024. Martinell expressed confidence that the additional data would support a positive regulatory outcome.
In the US, bluebird bio's gene therapy, Skysona (elivaldogene autotemcel), has been approved for cALD since 2022. However, bluebird bio has since withdrawn from the European market, making leriglitazone a potentially crucial treatment option if approved.
The CALYX trial, another ongoing study of leriglitazone, is evaluating the drug in adult male patients with progressive cALD. The combined data from NEXUS and CALYX are expected to provide a comprehensive dataset for regulatory review and potential approval of leriglitazone as a treatment for cALD.
