First Patient Dosed in NEXUS Phase 2 Trial of Leriglitazone in CALD

First Patient Dosed in NEXUS Phase 2 Trial of Leriglitazone in CALD

A Phase 2 trial evaluating leriglitazoneMinoryx Therapeutics‘ investigational oral therapy for boys with cerebral adrenoleukodystrophy (CALD), has dosed its first patient at Hospital Sant Joan de Déu in Spain, the company announced.

The NEXUS trial (EudraCT number 2019-000654-59) is enrolling up to 13 boys, ages 2–12, with early stage lesions evident on brain MRIs. Other recruitment sites include the University Medical Center Hamburg-Eppendörf and the University Hospital Göttingen, both in Germany, and the Bicêtre Hospital in France.

The European Medicines Agency (EMA) approved the company’s Pediatric Investigational Plan (PIP) for leriglitazone, meaning that positive results from NEXUS could support a request for its approval to treat children in Europe.

But the company plans to delay filing a full pediatric plan until it completes an ongoing Phase 2/3 trial of leriglitazone in men with adult-onset adrenoleukodystrophy (ALD), also called adrenomyeloneuropathy (AMN). Top-line results from this trial, at sites across Europe and the U.S., are expected by year’s end and may support a request that leriglitazone be approved for adults with AMN.

“This EMA approval of the PIP, based on the NEXUS trial, marks an important milestone for the company. It highlights the importance of making alternative safe and effective treatments available for children with early cALD,” María Pascual, chief regulatory officer of Minoryx, said in a press release.

“It not only provides a clear path for faster registration of leriglitazone in childhood cerebral ALD but also paves the way for submission of the MAA [marketing authorization application] in Europe for leriglitazone in adrenomyeloneuropathy, following successful completion of the ongoing Phase 2/3 ADVANCE trial,” Pascual added.

CALD is the most common and devastating form of ALD, with symptoms manifesting between the ages of 4 and 10. Adult AMN is usually less severe and progresses more slowly.

Leriglitazone, also known as MIN-102, is an oral PPAR gamma agonist that has the ability to cross the protective blood-brain barrier and enter the central nervous system (brain and spinal cord). Once there, it aims to prevent processes associated with ALD, including inflammation and oxidative stress, protecting nerve cells from damage.

In adults with AMN, the therapy is being investigated in the ADVANCE Phase 2/3 trial (NCT03231878); NEXUS is in children with CALD.

ADVANCE includes 116 male AMN patients, ages 18 to 65, randomly receiving leriglitazone or a placebo for two years. The trial’s main goal is to assess how the therapy impacts the AMN progression based on a motor function test, and patient-reported outcomes.

After completing the study, participants may opt to enter an open-label extension trial in which all will be given  the active treatment.

NEXUS is an open-label trial designed with input from both the U.S. Food and Drug Administration (FDA) and EMA, along with clinical experts and patient groups, to study leriglitazone in boys with CALD.

Participants must have with early evidence of brain lesions on MRI scans (with or without inflammation), but no signs of adrenal insufficiency.

As an open-label study, all enrolled are receiving leriglitazone. The trial’s main goal is to determine if the therapy can halt disease progression when given prior to a blood stem cell transplant, the current standard of care treatment for these patients. Secondary objectives include changes in neurological function, changes in brain inflammation, and overall survival.

“We are pleased that the first patient has been enrolled in the NEXUS trial and expect to report results in 2021, with the potential for preliminary results as soon as this year,” said Marc Martinell, CEO of Minoryx.

“With newborn screening currently being implemented, it is now possible to diagnose patients with early stage cALD,” said Patricia Musolino, the study’s principal investigator and a professor at Harvard Medical School. “There is an urgent need for alternative treatments that are less invasive than the current standard of care, which is based on hematopoietic stem cell transplantation.

“We look forward to further supporting the company and to bringing this much needed innovation to pediatric patients suffering from this devastating disease.”

Leriglitazone was designated an orphan drug by the FDA and EMA, and recently received the fast track status by the FDA for the treatment of ALD.

Orphan drug designation in Europe grants Minoryx a 10-year period of market exclusivity should the treatment be approved, and the company may be eligible for an additional two years after successful completion of the pediatric plan.

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