AMX0035's Potential in Tauopathies, Alkermes Initiates Phase 2 Study of ALKS 2680, EryDex Falls Short in Phase 3 ATTeST Trial

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

Newly published exploratory data from the phase 2 PEGASUS study of patients with early-stage Alzheimer disease (AD) showed that treatment with AMX0035 (Relyvrio), a previously approved drug for ALS, resulted in changes to multiple pathological pathways related to neurodegeneration, including reduced levels of phosphorylated tau 181 (p-tau) and total tau. Overall, these data further support the therapy’s potential to treat neurodegenerative diseases associated with tau dysfunction and tau aggregation, such as progressive supranuclear palsy (PSP).PEGASUS was a previously completed trial comprised of 95 participants with early-stage AD who were randomly assigned to AMX0035 (n = 51) or placebo (n = 44), for a 24-week period. Between the 2 groups, there were no differences in clinical efficacy outcomes on the primary end point of change in GST (between-group difference, 0.07; 95% CI, –0.08 to 0.21; P = .36); however, investigators concluded this was likely due to the small sample size and relatively short treatment duration.

According to a recent announcement, Alkermes has initiated a new phase 2 study, dubbed Vibrance-2 (NCT06555783) that will assess the therapeutic potential of ALKS 2680, an investigational, selective orexin 2 receptor (OX2R) agonist, as a treatment for patients with narcolepsy type 2 (NT2). This is the second phase 2 study in its development program, behind Vibrance-1, which includes those with narcolepsy type 1 (NT1). Vibrance-2, a double-blind, dose-range-finding, placebo-controlled study, will evaluate the efficacy and safety of 3 doses of ALKS 2680 (10 mg, 14 mg, or 18 mg) in comparison with placebo over an 8-week treatment period. The trial is expected to include 80 participants with a diagnosis of NT2, defined as narcolepsy without cataplexy, who will receive once-daily treatment. All patients who complete the double-blind portion of the study will have a chance to opt into an open-label safety extension, where additional monitoring will continue.

Newly announced data from the phase 3 ATTeST study (NCT02770807) revealed that EryDex (Quince Therapeutics) did not meet its primary end point of change in the modified International Cooperative Ataxia Rating Scale (mICARS) among pediatric patients with ataxia telangiectasia (A-T) after 6 months of treatment. Despite failing to meet the primary end point, the company noted that studies will continue to assess EryDex in patients aged between 6 and 9 years, based on subgroup analysis results from this trial. Published in The Lancet Neurology, the modified intention-to-treat (mITT) population in this trial comprised of 164 participants (low-dose group, n = 56; high-dose group, n = 54; placebo group, n = 54). Investigators reported no differences identified in regard to change in mICARS score from baseline to 6 months in the low-dose group (least squares mean difference, -1.37; 95% CI, -2.932 to 0.190) or the high-dose group (-1.40; -2.957 to 0.152; P = .0765) compared with the placebo group.

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