Minoryx gains FDA approval to initiate a Phase 3 clinical trial in patients with cerebral Adrenoleukodystrophy

US trial with leriglitazone to commence in mid-2023 providing an FDA-approved route to US market whilst EMA evaluates European Marketing Authorization Application (MAA)

Mataró, Barcelona, Spain, May 31, 2023 - Minoryx Therapeutics, a registration stage biotech company focused on the development of therapies for orphan central nervous system (CNS) disorders, today announces the US Food and Drug Administration (FDA) approval of its Phase 3 clinical trial (CALYX) of lead candidate leriglitazone, to treat adult male X-linked Adrenoleukodystrophy (X-ALD) patients with cerebral Adrenoleukodystrophy (cALD). More…

Minoryx presents topline results from Phase 2/3 study demonstrating significant clinical benefit for adrenomyeloneuropathy (AMN)

Largest prospective efficacy study conducted in the orphan disease AMN

  • Leriglitazone significantly reduces progression of cerebral lesions and myelopathy symptoms

  • Minoryx preparing for discussions with regulators for approval of leriglitazone for AMN patients

Mataró, Barcelona, Spain, January 26, 2021 - Minoryx Therapeutics, a Phase 3 clinical stage biotech company focused on the development of differentiating treatment options in orphan central nervous system (CNS) disorders, today announces topline results from its Phase 2/3 ADVANCE clinical trial. The study evaluated leriglitazone, a novel, selective PPARγ agonist, in male patients with adrenomyeloneuropathy (AMN), a neurodegenerative disease causing progressive spastic paraparesis and autonomic nervous system dysfunction. Additionally, AMN patients are at risk of developing progressive cerebral lesions, a devastating form of the disease leading to rapid severe disability and fatal if left untreated.

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ALD Newborn Screening Now in Texas!

It took a village to achieve’: Texas’ newborn screening lab now testing for ALD

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AUSTIN (Nexstar) — Newborn babies in Texas are now getting tested for adrenoleukodystrophy, commonly known as ALD. 

Texas joins 15 other states in testing for this condition in every baby born in the state. 

The rare genetic disorder occurs primarily in males and affects the nervous system, as well as the adrenal glands. It impacts around one in every 18,000 people. 

State health officials, legislators and parents toured the Texas Department of State Health Services’ newborn screening laboratory to celebrate the addition Thursday.

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Biomarker Identification, Safety, and Efficacy of High-Dose Antioxidants for Adrenomyeloneuropathy (AMN): a Phase II Pilot Study

Abstract

X-Adrenoleukodystrophy (X-ALD) and its adult-onset, most prevalent variant adrenomyeloneuropathy (AMN) are caused by mutations in the peroxisomal transporter of the very long-chain fatty acid ABCD1. AMN patients classically present spastic paraparesis that can progress over decades, and a satisfactory treatment is currently lacking. Oxidative stress is an early culprit in X-ALD pathogenesis. A combination of antioxidants halts the clinical progression and axonal damage in a murine model of AMN, providing a strong rationale for clinical translation. In this phase II pilot, open-label study, 13 subjects with AMN were administered a high dose of α-tocopherol, N-acetylcysteine, and α-lipoic acid in combination. The primary outcome was the validation of a set of biomarkers for monitoring the biological effects of this and future treatments. Functional clinical scales, the 6-minute walk test (6MWT), electrophysiological studies, and cerebral MRI served as secondary outcomes. Most biomarkers of oxidative damage and inflammation were normalized upon treatment, indicating an interlinked redox and inflammatory homeostasis. Two of the inflammatory markers, MCP1 and 15-HETE, were predictive of the response to treatment. We also observed a significant decrease in central motor conduction time, together with an improvement or stabilization of the 6MWT in 8/10 subjects. This study provides a series of biomarkers that are useful to monitor redox and pro-inflammatory target engagement in future trials, together with candidate biomarkers that may serve for patient stratification and disease progression, which merit replication in future clinical trials. Moreover, the clinical results suggest a positive signal for extending these studies to phase III randomized, placebo-controlled, longer-term trials with the actual identified dose. ClinicalTrials.gov Identifier: NCT01495260

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$100,000 Adrenomyeloneuropathy (AMN) Research Grant Awarded to Ali Fatemi, MD at The Kennedy Krieger Institute

The Stop ALD Foundation is excited to announce that the University of Pennsylvania's Orphan Disease Center has awarded a $100,000 research pilot grant to Dr. Ali Fatemi at The Kennedy Krieger Institute.

A significant hurdle for translating preclinical work into clinical trials for Adrenomyeloneuropathy (AMN) is the slowly progressive nature of AMN with extremely variable rates of progression. There is a critical need for surrogate biomarkers which can predict disease progression, or identify individuals who are rapid progressors. Effort is needed to be “clinical trial ready” so that therapeutic treatments can be tested for efficacy. 

This grant will fund assessment of existing Kennedy Krieger longitudinal magnetic transfer (MT) and diffuse tensor imaging (DTI) magnetic resonance imaging (MRI) of the brain and cervical spinal cord of AMN patients to look for significant changes over a 12-month period. In addition, standardized neuroimaging protocols will be implemented which can be executed at 4 main ALD Connect clinical trial centers. The identification and implementation of a multicenter imaging protocol for AMN is needed to allow the full implementation of the ALD Connect multicenter clinical trial network.

This work will serve as an important foundation for the broad research community, supporting a range of therapeutic approaches being studied by many dedicated researchers. 

This $100,000 grant was a result of the University of Pennsylvania Orphan Disease Center's annual Million Dollar Bike Ride. The Million Dollar Bike Ride focuses on raising money for rare disease research doubling the amount of money raised by its participants. The Stop ALD Foundation lead the ALD team and raised a total of $50,000, of which The Stop ALD Foundation contributed $40,000, amplifying donor money into important research areas. Dr. Fatemi’s grant will advance much-needed research.

Grant Awarded: $100,000

Project Title: Multicenter Cross Standardization of Magnetic Resonance Imaging Methods for Adrenoleukodystrophy/Adrenomyeloneuropathy.

Project Goal: Implement, cross standardize and validate MRI protocols necessary for clinical trials in Adrenomyeloneuropathy (AMN), the adult form of X-linked Adrenoleukodystrophy (ALD), for the ALD Connect Consortium.

Brief Background: Adrenomyeloneuropathy (AMN) is the adult variant of X-linked ALD and is a slowly progressive neurodegenerative disorder due to mutations in the peroxisomal AcylCoA transporter, ABCD1, with no current therapeutic options. However, over the last 10 years, at least 5 different biotechnology companies have developed a research and development program for AMN and encouraging results are emerging from preclinical studies. Furthermore, several neuroimaging methods have been studied in AMN and could serve as biomarkers. Yet, the conduction of clinical trials is hampered by rarity of the disorder and lack of standardized quantitative outcome measures. In an effort to overcome these issues, ALD Connect, a new consortium, was established a few years ago with the goal to cross-harmonize data collection. 

Importantly, MRI imaging protocols are not standardized between centers specialized in ALD for clinical trials, due to varying MRI scanner models and paradigms. In collaboration with Dr. Seth Smith, we have developed tools that will allow the harmonization of imaging protocols between the nation’s five main clinical sites.

Specific Aims:

  • Aim 1: Develop a standardized imaging protocol and MRI sequence for AMN trials which is executable by all included site MRI scanners and infrastructure.
  • Aim 2: Implement imaging protocols by performing on-location MRI brain scans of a single healthy control subject at each trial site. Assess equivalency of MRI scan data between sites at The Kennedy Krieger Institute, and implement necessary protocol changes at the trial sites. Establish a communication and review platform between AMN and imaging experts for the trial sites as a multi-center imaging network.

2017 Million Dollar Bike Ride Pilot Grant Program: Request for Applications

The 2017 Million Dollar Bike Ride Pilot Grant Program is now open!  The MDBR Pilot Grant Program provides a one-year grant to support research related to a rare disease represented in the 2017 Million Dollar Bike Ride. Thirty-three (33) total grant opportunities are listed below.

Eligibility: All individuals holding a faculty-level appointment at an academic institution or a senior scientific position at a non-profit institution or foundation are eligible to respond to this RFA.  

To Apply:  Please review the RFA guidelines here.  Interested applicants must first submit a Letter of Interest (LOI) which can be found here.  This LOI is due by Monday, September 18, 2017 by 8pm EST.   Full applications are accepted by invitation only after LOIs are approved. 

Research Focus Areas for Pilot Grants:

1) Adrenoleukodystrophy (ALD): One $101,164 pilot grant is available with a focus on a path towards treatment for Adrenomyeloneuropathy (AMN). Grants should focus on activities that lead towards a clinical trial.  Adrenoleukodystrophy (ALD) is an X-linked metabolic disorder, characterized by progressive neurologic deterioration due to demyelination of the cerebral white matter. The adult form, Adrenomyeloneuropathy (AMN), develops in young adulthood and in general, progresses more slowly than ALD. Beginning in their 20s and 30s, men and ~60% of women carriers exhibit neurological-based motor lesions in their extremities. These lesions progress over many years and are characterized by progressive spasticity, ataxia, incontinence, and sexual dysfunction that can also be accompanied by fatigue and depression. ALD/AMN can lead to severe disability. All current treatments are symptomatic and do not address the progressive nature of the disease. This grant is made possible by Team Stop ALD and the Stop ALD Foundation.

$100,000 AMN Research Grant Awarded to Dr. Florian Eichler, Massachusetts General Hospital

The Stop ALD Foundation is excited to announce that the University of Pennsylvania's Orphan Disease Center has awarded a one-year, $100,000 research pilot grant to Dr. Florian Eichler at Massachusetts General Hospital. Dr. Eichler and his team have already established an Adrenomyeloneuropathy (AMN) animal model proof of concept showing a gene therapy approach could provide benefit where no treatment is currently available. Today when young men with Adrenoleukodystrophy (ALD) begin showing adult-onset signs of AMN, they slowly lose their ability to walk. This pilot grant will help move Dr. Eichler's research program forward towards human studies. However, additional funds will still be necessary to initiate the study.

This $100,000 grant was a result of the Penn Orphan Disease Center's annual Million Dollar Bike Ride. The Million Dollar Bike ride focuses on raising money for rare disease research doubling money raised. The Stop ALD Foundation lead the ALD Team and raised a total of $50,000 of which The Stop ALD Foundation contributed $40,000, amplifying donor money into important research areas. Dr. Eichler's grant will advance much-needed research into a promising treatment for Adrenomyeloneuropathy (AMN). This $100,000 pilot grant is just the beginning and we encourage other donors and foundations to fund this important AMN research further to help it move towards a clinical trial.

$100,000 ALD/AMN Research Grant. Application Due Sept 23, 2016

2016 Million Dollar Bike Ride Grants

The 2016 Million Dollar Bike Ride Pilot Grant Program is now open!  The MDBR Pilot Grant Program provides a one-year grant to support research related ALD/AMN. 

Eligibility: All individuals holding a faculty-level appointment at an academic institution or a senior scientific position at a non-profit institution or foundation are eligible to respond to this RFA.  

To Apply: Please be sure to read the MDBR RFA Guidelines before applying.  Submit your Letter of Interest (LOI) via the link below no later than Friday, September 23, 2016 by 8pm EST. Full application is by invitation only, after review of LOIs. 

LOI Submission Form: LOI Submission Form  Due 9/23/16 by 8pm EST. 

Research Focus Areas for Pilot Grant:

Adrenoleukodystrophy (ALD): One $100,000 pilot grant is available with a focus on a path towards treatment for Adrenomyeloneuropathy (AMN). Adrenoleukodystrophy (ALD) is an x-linked metabolic disorder, characterized by progressive neurologic deterioration due to demyelination of the cerebral white matter. The adult form, Adrenomyeloneuropathy (AMN), develops in young adulthood and in general, progresses more slowly than ALD. Beginning in their 20s and 30s, men and ~60% of women carriers exhibit neurological-based motor lesions in their extremities. These lesions progress over many years and are characterized by progressive spasticity, ataxia, incontinence, and sexual dysfunction that can also be accompanied by fatigue and depression. ALD/AMN can lead to severe disability. All current treatments are symptomatic and do not address the progressive nature of the disease. This grant is made possible by Team Stop ALD and the Stop ALD Foundation.

Secretary of Health and Human Services accepts the recommendation to expand the Recommended Uniform Screening Panel to include X-ALD and MPS I

Secretary of Health and Human Services Sylvia Mathews Burwell, accepted the recommendation to expand the Recommended Uniform Screening Panel (RUSP) to include the addition of X-linked Adrenoleukodystrophy (X-ALD) and Mucopolysaccharidosis type 1 (MPS I). The Affordable Care Act requires that most health plans cover evidence-based preventative care and screenings provided for in the comprehensive guidelines supported by Health Resources and Service Administration (HRSA).

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RFA for $50,000 for AMN research

The 2015 Million Dollar Bike Ride Pilot Grant Program is now open.  Please first review the RFA guidelines before submitting your pre-application using the webform below.  All pre-application submissions are due Monday, September 14, 2015 by 5:00 pm (EST).  If your pre-application is approved, you will be notified with an invitation to submit a full-application, due October 19, 2015.

For questions regarding this pilot grant program, please contact Samantha Charleston at scharle@mail.med.upenn.edu, or (215) 573-6822.

Click here to view the 2015 MDBR Pilot Grant RFA Guidelines: 2015 MDBR Pilot Grant RFA Guidelines

Click here to submit your pre-application: 

Research Focus Areas for Pilot Grants:

Adrenoleukodystrophy (ALD): Adrenoleukodystrophy, or ALD, is an x-linked metabolic disorder, characterized by progressive neurologic deterioration due to demyelination of the cerebral white matter. The adult form, known as Adrenomyeloneuropathy (AMN) develops in young adulthood, and in general, they progress more slowly. Beginning in their 20s and 30s, these young men exhibit neurological based motor lesions in their extremities. These lesions progress over many years and are inevitably accompanied by moderate to severe handicap. In approximately one third of these patients the central nervous system also becomes involved.

One $50,000 pilot grant is available with a focus on treatments for Adrenomyeloneuropathy (AMN), the adult form of the disease. We are interested in proposals that would provide a path towards a treatment, including advancing the understanding of what can be used as endpoints when conducting an AMN trial. This grant is made possible by Team Stop ALD and the Stop ALD Foundation.

Governor Signs Righter Legislation for Newborn Screening

Legislation requiring the Illinois Department of Public Health to provide all newborns with screening tests for the presence of adrenoleukodystrophy (ALD) under a new law sponsored by State Sen. Dale Righter (R-Mattoon) was signed Wednesday by Gov. Bruce Rauner.

“Screening for ALD at such an early stage will help save lives,” Righter said. “All too often, those with ALD are diagnosed too late for treatment to work. It’s a terrible disease, but this law helps us get out in front of it and save our children.”  More...