Ublituximab Outperforms Teriflunomide on ARRs, CNM-Au8 Fails HEALEY ALS Trial, Benefits of Aerobic Exercise in Multiple Sclerosis

Welcome to this special edition of Neurology News Network. I’m Marco Meglio.

Data from ULTIMATE I and II, a recent pair of phase 3 trials, showed that ublituximab, in investigational treatment developed by TG Therapeutics, resulted in lower annualized relapse rates (ARRs) and fewer brain lesions on MRI than teriflunomide for patients with relapsing multiple sclerosis (MS) over the duration of 96 weeks.The ARR was 0.08 with ublituximab and 0.19 with teriflunomide from the ULTIMATE I trial, while the ARR was 0.09 and 0.18 in the ULTIMATE II. Ublituximab produces B-cell depletion and enhances antibody-dependent cellular cytolysis, which could be beneficial treatment for patients with relapsing MS. The findings additionally showed a significantly lower risk of worsened disability with ublituximab treatment. Although, the investigational therapy was also associated with infusion-related reactions, which occurred in 47.7% of the participants in the ublituximab group. One of the limitations of conducting the trials is that no inferences were able to be made regarding the efficacy of ublituximab in comparison with other therapies for MS that are more potent than teriflunomide.

Topline findings from the pivotal HEALEY ALS trial, the first-ever platform trial for ALS, demonstrated that CNM-Au8 did not meet its primary and secondary end points; however, the therapy did show survival benefit on exploratory analyses.All told, over a 24-week period, treatment with the investigational gold nanocrystal suspension resulted in 2% slowing of disease progression, demonstrated by scores on ALS Functional Rating Scale Revised (ALSFRS-R) adjusted for mortality. Prespecified survival analyses showed significant survival benefit for those in the 30-mg CNM-Au8 group, which the company noted warrants continued development. No survival benefit was observed for the 60-mg CNM-Au8 group, the larger of the 2 doses assessed. The news comes less than a week after another ALS hopeful, Biohaven’s enzyme inhibitor verdiperstat, also failed to statistically differentiate itself from placebo in HEALEY ALS.

Data from the randomized, controlled Early Multiple Sclerosis Exercise, or EMSES, study suggest that early supervised aerobic exercise does positively affect the microstructural integrity of important motor-related tracts and nuclei in patients with multiple sclerosis. Notably, though, the supervised exercise regimen did not reduce relapse rates or global brain atrophy—the study’s primary outcome measures—but the investigators, including Ulrik Dalgas, PhD, MSc, associate professor of public health, Aarhus University, noted that “exercise is a promising nonpharmacological approach,” and to this point, the window of opportunity for intervention that is suspected to exist early in the disease course has been mostly uninvestigated. Particularly, they wrote, “Potential supplemental disease-modifying and neuroprotective treatment strategies are warranted in multiple sclerosis.” All told, the data from MRI findings showed that microstructural integrity was higher in 50% a priori defined motor-related tracts and nuclei in the exercise group (n = 84) compared with the population-based Danish MS Registry control group (n = 850) at 48 weeks.

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