Phase 2 pegsebrenatide trial begins dosing in progressive MS
Study will track brain volume, disability, and other disease measures
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GLP-1 receptor agonists are being explored beyond diabetes and weight loss, including in neurodegenerative diseases such as progressive MS. (Photo by iStock)
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A Phase 2 trial has begun testing pegsebrenatide, also known as NLY01, in progressive MS.
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The therapy is designed to activate GLP-1 receptors and modulate neuroinflammation.
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The study will track brain volume changes as a measure of neurodegeneration.
The first participant has been dosed in an investigator-initiated Phase 2 clinical trial testing Neuraly‘s experimental medication pegsebrenatide as a potential treatment for progressive forms of multiple sclerosis (MS).
Called TAG-MS (NCT07497399), the study is being led by Ellen Mowry, MD, at Johns Hopkins University in Maryland, with additional clinical sites expected to participate. The plan is to include about 120 adults with progressive MS who are clinically stable on MS therapy for at least one year, with no relapses or new brain MRI lesions during that time.
“We are excited to advance the clinical development of pegsebrenatide in collaboration with leading MS research centers,” Seulki Lee, CEO of Neuraly, said in a company press release.
Pegsebrenatide aims to target neuroinflammation in MS
MS is an autoimmune disease marked by mistaken immune attacks in the brain and spinal cord, leading to inflammation, damage to myelin — the protective coating around nerve fibers — and nerve cell injury. While relapsing forms of MS are marked by periods of worsening symptoms that alternate with periods of recovery and relative stability, progressive forms of MS tend to involve gradual disability worsening over time, usually with fewer or less distinct relapses.
Although several therapies can reduce inflammatory disease activity in relapsing MS, treatment options remain limited for progressive forms of the disease.
Pegsebrenatide, also known as NLY01, is designed to modulate neuroinflammatory pathways and protect neurons, with the goal of addressing processes thought to drive ongoing nerve damage and disability worsening in progressive MS.
The medication is designed to activate the glucagon-like peptide-1 (GLP-1) receptor. GLP-1 receptor agonists are best known to many people as medications used for diabetes or weight loss.
But pegsebrenatide was developed for neurodegenerative diseases, and is intended to modulate the activity of microglia and astrocytes — support cells in the brain and spinal cord that can become activated and fuel neuroinflammation. Such inflammation is thought to contribute to neurodegeneration, or the gradual damage and loss of nerve cells.
Preclinical research has suggested that NLY01 can reduce inflammatory immune activity and ease disease severity in a mouse model of MS.
The TAG-MS trial will now test whether pegsebrenatide can provide benefits for people with progressive MS.
Study will track brain volume changes over nearly two years
Participants will be randomly assigned to receive weekly subcutaneous, or under-the-skin, injections of pegsebrenatide or a placebo for 96 weeks, or nearly two years. Treatment will begin at a lower 5 mg dose for the first four weeks, then increase to 10 mg, with dose adjustments allowed if needed due to side effects.
The trial’s main goal is to measure changes in normalized brain parenchymal volume, an MRI-based measure of brain tissue volume. The loss of brain volume, or brain atrophy, reflects the loss of nerve tissue that occurs as the disease progresses, and slower rates of brain atrophy could suggest the therapy is helping to slow neurodegeneration.
Researchers will also assess changes in the volume of specific brain regions as secondary measures, as well as changes in the retina, the light-sensitive layer at the back of the eye. Such retinal changes may reflect nerve damage in MS. Other outcome measures include physician-rated disability assessments, patient-reported measures of physical function and quality of life, and safety outcomes.
“Pegsebrenatide represents a differentiated therapeutic strategy aimed at addressing the underlying neuroinflammatory processes that drive neurodegeneration,” Lee said. “We believe this program has the potential to expand the treatment paradigm for progressive MS and other neurodegenerative diseases.”
Pegsebrenatide has been studied in a Phase 2 trial for Parkinson’s disease, and Neuraly is also developing it for Alzheimer’s disease.
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