Fenebrutinib Achieves Primary End Point in Head-to-Head Trial, GB221 Begins First-in-Person Trial for SMA1, Air Pollution Linked to Increased AD Risk

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Welcome to the Neurology News Network. My name is Louie Pasculli. Here’s a look at this week’s top stories in neurology.

Beginning with phase 3 data, Genentech has reported that its pivotal phase 3 FENhance 1 study assessing investigational Bruton’s tyrosine kinase (BTK) inhibitor fenebrutinib against teriflunomide (Aubagio; Sanofi), an approved treatment for relapsing forms of multiple sclerosis (RMS), met its primary end point in reducing annualized relapse rate. All told, findings showed that treatment with fenebrutinib reduced the ARR by 51% compared with teriflunomide over at least 96 weeks, which was consistent with results from the previously completed FENhance 2 (NCT04586023) study, which showed a 59% reduction in ARR among patients with RMS. The company also reported that secondary end points in both FENhance studies displayed statistically significant reductions in brain lesions and that all progression end points showed favorable trends for fenebrutinib. Carrie Hersh, DO, MSc, FAAN, associate professor of neurology at Cleveland Clinic Lerner College of Medicine, told NeurologyLive®. “The positive phase 3 results of FENhance 1 are exciting and validating for the BTK inhibitor class, particularly given the long pursuit of therapies that can meaningfully impact both relapsing and progressive MS. Seeing consistent efficacy in a large program suggests fenebrutinib may represent a true advance rather than a signal limited to early-phase data. If approved, fenebrutinib could expand our therapeutic toolkit with an oral, higher efficacy option that targets B-cell biology and innate immune mechanisms in a novel way. The potential to address inflammatory activity while also impacting progression, especially in primary progressive MS, could meaningfully influence treatment sequencing and long-term disease management strategies.”

Taking a look at gene therapy news, a first-in-human clinical trial evaluating the investigational gene therapy GB221 for spinal muscular atrophy type 1 (SMA1) has begun dosing pediatric participants, according to a company announcement from Gemma Biotherapeutics (GEMMABio). The phase 1/2 CHARISMA clinical trial is designed to assess the safety, tolerability, and preliminary efficacy of a next-generation adeno-associated virus (AAV) gene therapy administered via intracisterna magna (ICM) injection in infants with SMA1. SMA1 is a severe form of SMA and typically presents within the first 6 months of life. CHARISMA is a first-in-human clinical study evaluating GB221 in infants aged 2 weeks to younger than 12 months, including both symptomatic and presymptomatic participants. The study will assess safety and tolerability as primary outcomes, with exploratory efficacy assessments including motor function and developmental milestones.

Concluding with environmental risks, Alzheimer Disease (AD) prevalence continues to rise and more attention is turned toward identifying modifiable environmental risk factors. In a new national cohort study, lead author Yanling Deng, MBBS, PhD, postdoctoral researcher at Emory University, and colleagues examined the association between air pollution exposure and AD risk. Published in PLOS Medicine, findings suggest that PM2.5 exposure is linked to increased AD risk, largely through direct pathways rather than through comorbid conditions. To gain more perspective on these new nationwide findings linking PM2.5 exposure to increased AD risk, NeurologyLive® recently spoke with AD expert R. Scott Turner, PhD, MD, the director of the memory disorders program at MedStar Georgetown University Hospital. In this Q&A, he underscored the importance of identifying modifiable environmental factors as AD prevalence is projected to rise. He also noted that PM2.5 may function as an independent risk factor through mechanisms such as inflammation, oxidative stress, and amyloid accumulation.

To read the full interview and to get more direct access to expert insight, head to NeurologyLive.com. Be sure to tune in next week to stay up to date on the latest in neurology. I’m Louie Pasculli and thanks for watching Neurology News network.