Apitegromab Improves Quality of Life in SMA, ARB Therapy Leads to Lowered Epilepsy Risk, Donanemab Reduces Alzheimer-Related Plasma Biomarkers

Neurology News Network for the week ending October 28, 2022. [WATCH TIME: 4 minutes]

WATCH TIME: 4 minutes

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

Newly announced data from the phase 2 TOPAZ trial showed that apitegromab (SRK-015; Scholar Rock), an investigational candidate for the treatment of spinal muscular atrophy (SMA), helped improve quality of life in nonambulatory patients with types 2 and 3 SMA after 24 months of treatment. These findings, presented at the third International Scientific Congress on SMA in Barcelona, Spain, are relevant for informing the therapeutic hypotheses being evaluated in the phase 3 SAPPHIRE trial. The analysis assessed activities of daily living (ADL), fatigue, and muscle endurance by 3 tertiary end point measures. They included the Pediatric Evaluation of Disability Inventory-Computer Adaptive Test (PEDI-CAT), Patient Reported Outcome Measurement Information System (PROMIS), and Endurance Shuttle Box and Block Test. or nonambulatory type 2 patients, 24-month treatment with apitegromab resulted in stabilization or continuous improvements in ADL, as demonstrated by a mean change from baseline of 3 points in PEDI-CAT scores and a mean change of 5 points in PROMIS scores.

In a comparison study of antihypertensive medications, findings showed that angiotensin receptor blocker (ARB) therapy was significantly associated with a decreased risk of epilepsy in those with hypertension. A total of 168,612 patients with hypertension were included in propensity score matching, with 42,153 each on an antihypertensive drug of either ß-blockers, ARBs, angiotensin-converting enzyme inhibitors, or calcium channel blockers. Cox regression models were used to study the association between the incidence of epilepsy and ARBs compared with all other antihypertensive drug classes as a group. Because of the matched-pair study design, all 4 cohorts had the same age, sex, and comorbidity structure. A documented diagnosis of epilepsy within 5 years after the index date was lowest in those treated with ARBs and at its highest among those receiving ß-blockers and CCBs.

Recently published secondary findings from the phase 2 TRAILBLAZER-ALZ study showed that treatment with donanemab, an investigational therapy that targets a modified form of amyloid-ß called N3pG, resulted in significant reductions in plasma biomarkers pTau217 and glial fibrillary acidic protein (GFAP) compared with placebo.In a cohort of 272 men and women aged 60 to 85 years with early symptomatic AD, the mean plasma pTau217 levels decreased by 23% from baseline to week 76 after treatment with donanemab, whereas levels continued to rise by 6% in those on placebo. Similarly, mean plasma GFAP levels decreased by 12% from baseline while levels continued to rise by 15% for those on placebo. No significant between-group differences were observed for neurofilament light (NfL) levels. Participants in the study were randomly assigned 1:1 to receive intravenous donanemab or placebo every 4 weeks for up to 72 weeks. The first 3 doses of donanemab were given at 700 mg and then increased to 1400 mg.

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