Phase 3 LIGHTHOUSE Study Initiated, Trend Toward ASMs With Lower Teratogenic Risk, Rituximab Effects on NMOSD, MOGAD


Neurology News Network for the week ending October 15, 2022. [WATCH TIME: 3 minutes]

WATCH TIME: 3 minutes

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

Dosing for the large-scale, phase 3 LIGHTHOUSE study evaluating the safety and efficacy of BIIB122 (Biogen/Denali Therapeutics), an investigational agent for patients with Parkinson disease (PD) with a confirmed pathogenic mutation in the LRRK2 gene, has commenced.BIIB122, a small molecule inhibitor of LRRK2 discovered and initially developed by Denali, will be assessed in a cohort of 400 individuals with genetically mutated PD. In the multicenter, double-blind study, individuals will be randomly assigned to either 225-mg BIIB122 tablets, orally once daily, for up to 180 weeks, or matching placebo. The primary outcome measures include the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Parts II and III, which evaluates experiences of daily living and motor signs of PD, respectively. Mutations in the LRRK2 gene represent 1 of the most common genetic causes of PD, explaining an estimated 4% to 5% of familial and 1% to 2% of sporadic PD cases.

In a Japan-based cohort study of pregnant outpatient women with epilepsy who visited hospitals between 2016 and 2020, findings showed a temporal trend toward antiseizure medications (ASMs) with lower teratogenic risk, such as levetiracetam and lamotrigine, whereas prescriptions for valproic acid remained relatively unchanged.Over the 5-year stretch, the numbers of pregnant women with epilepsy were 404, 421, 368, 378, and 386. The data showed that the proportions of levetiracetam and lamotrigine prescriptions significantly increased from 19.1% to 30.8% and from 12.1% to 18.4%, respectively, during that time period. In contrast, there was no temporal change in the proportion of valproic acid prescriptions, which was 12.4% in 2016 and 10.1% in 2020. Previous literature has shown that valproic acid is associated with a variety of major and minor malformations, including a 20-fold increase in neural tube defects, cleft lip and palate, cardiovascular abnormalities, developmental delay, endocrinology disorders, limb defects, and autism.

A recent retrospective observational study from Johns Hopkins resulted in rituximab treatment being significantly associated with a reduced relapse rate for patients with neuromyelitis optica spectrum disorder (NMOSD) and MOGAD. Previous data on using rituximab in long-term, such as with the effectiveness and safety of the treatment, were limited.Relapses on rituximab occurred in 28% of NMOSD patients (n = 31) and 61% of MOGAD patients (n = 14). Seventy-seven percent of NMOSD treatment failures happened in the setting of delayed/missed rituximab doses and/or peripheral B cell reconstitution (24 relapses) or within the initial 6-months after starting rituximab (13 relapses). Whereas the patients with MOGAD had a treatment failure rate of 54%, a smaller proportion.

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