MS Medications Added to WHO Essential List, Epigenome Therapy Shows Efficacy in AD, Phase 3 NEURO-TTransform Results Announced

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

The World Health Organization (WHO) published new editions of the Model Lists of Essential Medicines (EML) and Essential Medicines for Children (EMLc), which now include 3 new therapies for the treatment of multiple sclerosis. Launched in 1977 to promote better access to medicines in developing countries, the WHO Model Lists have become a global policy tool for decisions related to the selection and universal coverage of medicines within all health systems. In a meeting of the WHO Expert Committee on the Selection and Use of Essential Medicines, held April 24-28 at the WHO Headquarters in Geneva, the committee considered and reviewed 85 applications for medicines to be added. In total, the updated EML includes 24 new medicines for adults and 12 new medicines for children for the treatment of several conditions, including MS, cancer, infectious diseases, cardiovascular conditions, and more. In addition, the update adds new formulations of 19 medicines to the EML and 48 medicines to the EMLc.

In a recent study using an epigenome therapy strategy, the candidate demonstrated efficacy in editing of apolipoprotein (APOE) and APOE e4 expressions in human induced pluripotent stem cells (hiPSC) -derived neurons and the human isogenic APOEe4 organoids, ultimately reducing the levels of APOE-mRNA and the protein in both models.1 These findings provided in vitro and in vivo proof-of-concept of the therapy’s efficacy and suggests the candidate's ability to fine-tune APOE expression is translational toward the development of a therapeutic approaches to prevent or delay late-onset Alzheimer disease (AD). Using this therapy approach there were no detectable editing of the e3 allele in the isogeneic hiPSC-derived neurons, and organoids homozygous for the e3 allele. Adeno-associated- dCas9-KRAB-MeCP2 vector injected into the hippocampus of APOEe4 and APOEe3 mice, performed in vivo studies, demonstrated between a 50-70% decrease in the mRNA and protein. Researchers noted a similar effect using the lentivirus- CRISPR/Cas system to target ApoEe4 in the same allele-specific way.

Newly announced phase 3 findings from the NEURO-TTRansform study showed that treatment with eplontersen resulted in halted neuropathy progression and improved quality of life at 85 weeks in patients with hereditary transthyretin-mediated amyloid polyneuropathy (ATTRv-PN). Currently under review with the FDA, a decision on eplontersen as a potential therapy for ATTRv-PN is expected by December 22, 2023. NEURO-TTRansform was an open-label study where patients were randomly assigned 6:1 to eplontersen (n = 144) or inotersen (Tegsedi), AstraZeneca’s previously approved therapy for hATTR, for a 66-week double-blind period, followed by an open-label extension. The study also included a 60-patient external placebo control group. At week 85, investigators observed a mean reduction of 81.8% in serum TTR concentration relative to baseline for eplontersen-treated patients.

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