Diazepam Increased Time Between Cluster Intervals, Higher Dose Nusinersen Shows Extra Benefit, Lecanemab BLA Submitted

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Results from an exploratory analysis of a 12-month study demonstrated that treatment with diazepam nasal spray (Valtoco; Neurelis) significantly increased the time between interseizure cluster intervals (ISCIs), which may reflect a salutary effect of cluster treatment.From period 1 to period 4, the mean ISCIs for the 76-patient cohort increased significantly, from 12.2 days to 25.7 days (P <.01). Presented at the 2nd North American Epilepsy Congress, held virtually May 5-8, 2022, the study investigators concluded that these findings "raise the possibility that intermittent treatment alters the underlying biology of clusters, which should be evaluated in further studies."The phase 3 open-label, repeat-dose study included 163 patients with seizure clusters (SCs), aged 6 to 65 years, who received at least 1 dose of diazepam nasal spray. ISCIs were evaluated using 90-day periods for patients treated with at least 2 doses across period 1 and the following 3 periods. Of 151 patients with ISCI data, 120 had data in period 1 and another period, while 76 individuals had at least 1 ISCI in periods 1 to 4, or across the 1-year stretch.

Using data from the phase 2 CS3A (NCT01839656) and ENDEAR studies (NCT02193074), investigators found that treatment with nusinersen (Spinraza; Biogen) at doses higher than the approved 12-mg dose may lead to additional clinically meaningful improvement in patients with infantile-onset spinal muscular atrophy. Led by Richard Finkel, MD, director, Center for Experimental Neurotherapeutics, St. Jude Children’s Research Hospital, the mean percentage reductions from baseline in plasma phosphorylated neurofilament heavy chain (pNF-H) levels among those treated with 6-mg and 12-mg nusinersen loading doses in CS3A at day 85 were 25.0% and 62.7%, respectively. In those studies, patients received 3 loading doses, whereas in ENDEAR, a 12-mg nusinersen regimen with 4 loading doses resulted in the greatest decrease (71.4%) in plasma pNF-H levels at day 64. As expected, the lowest nusinersen cerebral spinal fluid (CSF) levels were observed in the CS3A group treated with the 6-mg, 3 loading dose regimen (1.1 ng/mL at day 85). In contrast, higher nusinersen CSF levels were seen in the CS3A group treated with 3, 12-mg loading doses (3.7 ng/mL at day 85), and the highest levels were observed in the ENDEAR group treated with the 12-mg, 4 loading dose regimen.

After beginning their process in September 2021, Eisai and Biogen have officially submitted a biologics license application (BLA) for lecanemab (BAN2401), an investigational agent for the treatment of mild cognitive impairment (MCI) because of Alzheimer disease (AD) and mild AD. The anti-amyloid-ß (Aß) protofibril antibody was submitted under the accelerated approval pathway, with an expected Prescription Drug User Fee Act (PDUFA) date still being determined.The application is supported by data from the phase 2b clinical trial, known as Study 201 (NCT01767311), which demonstrated a reduction in brain amyloid accompanied by a consistent reduction of decline across several clinical and biomarker end points in patients with MCI because of AD or Alzheimer dementia. Additionally, the agency agreed that the completed results of the phase 3 Clarity AD study (NCT03887455), an ongoing trial, can serve as a complementary study to verify the clinical benefit of lecanemab post accelerated approval.

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