News #AANAM – Ibudilast Slows Brain Atrophy in PPMS But Not SPMS Patients, Phase 2b Trial Shows #AANAM – Ibudilast Slows Brain Atrophy in PPMS But Not SPMS Patients, Phase 2b Trial Shows by Jose Marques Lopes, PhD | April 4, 2019 Share this article: Share article via email Copy article link Treatment with oral ibudilast slows brain shrinkage in patients with primary progressive multiple sclerosis (PPMS), but not in those with secondary progressive MS (SPMS), according to results of a Phase 2b clinical trial. According to the findings, this could be partially due to faster disease progression in untreated controls with PPMS. The study, “Response to Treatment According to Progressive Disease Type: Analysis from a Phase II Progressive MS Trial of Ibudilast,” will be presented at the 2019 American Academy of Neurology (AAN) Annual Meeting, taking place May 4–10 in Philadelphia. Andrew Goodman, MD, an investigator in the study and a professor at the University of Rochester School of Medicine and Dentistry, will discuss the data May 6 in the Platform Presentation 007: Session S12 Progressive Multiple Sclerosis. Although PPMS and SPMS have been increasingly regarded as having more similarities than differences, whether they differ in response to treatment is still unclear. To address this, scientists evaluated the impact of ibudilast on brain atrophy in these two types of progressive disease, as part of the SPRINT-MS (NCT01982942) trial. This 96-week, randomized, and double-blind study compared treatment with MediciNova’s investigational therapy with a placebo in 255 adults (ages 21–65) — 134 with PPMS and 121 with SPMS. Participants took up to 100 mg of ibudilast in oral capsules per day. Previously reported results from SPRINT-MS showed a 48% slowing in brain atrophy progression relative to placebo, as assessed by a measure called brain parenchymal fraction. This translates to a decrease of approximately 2.5 milliliters in brain tissue loss. A subsequent, or post-hoc, analysis has now revealed that ibudilast significantly slowed brain atrophy in patients with PPMS, but not in those with SPMS. According to the investigators, this may have been driven at least partially by the results in people on placebo, as controls with PPMS showed faster atrophy progression than controls with SPMS. When analyzing PPMS and SPMS patients together, treatment with ibudilast showed a trend toward slowed brain atrophy even after accounting for differences in age, T2 lesion volume — which refers to the total amount of lesions, both old and new — and retinal nerve fiber layer thickness. “The overall treatment effect of ibudilast on progression of brain atrophy in progressive MS appears to be driven by patients with PPMS, which may in part be because of their faster atrophy progression rates in untreated patients,” the researchers wrote. Ibudilast is a small molecule therapy that acts on several sites in the brain, preventing immune cells called macrophages from migrating, among other effects. As a result, ibudilast suppresses the production of pro-inflammatory molecules called cytokines, and promotes the generation of growth factors. According to a press release, MediciNova will give two other presentations at the AAN meeting regarding SPRINT-MS results. Both will be part of Poster Session 3: MS Clinical Trials and Therapeutic Research on May 7. The study, “Effect of Ibudilast on Neurofilament-light Chain in Progressive MS: Analysis from a Phase 2 Trial,” will be presented by Robert Fox, MD, a principal investigator in the trial and vice chair for research at the Mellen Center for Multiple Sclerosis at Cleveland Clinic. Fox will present findings of ibudilast’s effect on a biomarker of nerve cell damage, called neurofilament light, in the serum and cerebrospinal fluid — the liquid surrounding the brain and spinal cord. The other study, “Effect of ibudilast on macular measures in progressive MS: OCT analysis from a phase 2 trial” will be presented by Robert Bermel, MD, medical director of the Mellen Center for Multiple Sclerosis. He will present results showing that ibudilast reduces volume loss in the eye’s macula, and decreases thinning of the ganglion cell/inner plexiform layer, also in the macula. Print This Page About the Author Jose Marques Lopes, PhD José holds a PhD in neuroscience from the University of Porto, Portugal. After postdocs at Weill Connell Medicine and Western University, where he studied the processes driving hypertension and Alzheimer’s disease, he moved on in 2016 to a career in science writing and communication. José is the author of several peer-reviewed papers and a book chapter and has presented his research in numerous international meetings. Tags AAN 2019, AANAM, brain atrophy, Ibudilast, MediciNova, PPMS, SPMS, SPRINT-MS
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