ADDRESS-LC Study of Long COVID Initiated, Phase 4 Trial Testing IVIg Transition to Efgartigimod, Lack of Rebound Effect Seen in Ozanimod

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

According to a recent announcement, BioVie had its first patients dosed in a phase 2 study, dubbed ADDRESS-LC (NCT06847191) that tests the therapeutic potential of bezisterim, a blood brain barrier-permeable, insulin-sensitizer, as a treatment for neurological symptoms associated with Long COVID. The newly initiated study is a randomized, placebo-controlled trial consisting of 200 patients with Long COVID who have cognitive impairment sequelae and fatigue for at least 3 months. Funded by a grant from the Department of Defense, the study assigns patients to either bezisterim or placebo twice daily for 84 days, using change in performance on the Cogstate Cognition battery as the primary outcome measure. Initial data from the trial is expected to be released in the first half of 2026.

At the 2025 Peripheral Nerve Society (PNS) Annual Meeting, held May 17-20, in Edinburgh, Scotland, investigators presented the design of a phase 4, open-label trial testing the safety and efficacy of transitioning from intravenous immunoglobulin (IVIg) to efgartigimod (Vyvgart Hytrulo; argenx) in patients with chronic demyelinating inflammatory polyneuropathy (CIDP). Efgartigimod, originally approved for myasthenia gravis, became the first and only neonatal Fc receptor (FcRn) blocker approved for the treatment of CIDP in 2024. In the phase 3 ADHERE trial (NCT04281472)–the study used for its expanded indication–participants underwent a washout period during which they were required to show disease worsening before initiation of treatment with efgartigimod. Through this new trial, which began recruitment in Q4 2024, investigators will look to better understand how to safely transition from IVIg to efgartigimod without requiring disease worsening.

An analysis of DAYBREAK, a phase 3, single-arm, open-label extension study (NCT02576717) revealed that treatment with ozanimod (Zeposia; BMS) did not result in higher-than-expected disease activity indicative of a rebound effect in either women or men with relapsing multiple sclerosis (MS). While relapse rates were slightly higher among women, these findings were consistent with previously reported rates. Rebound effect, referring to clinical and/or radiological worsening of disease activity, is a well-documented concern with certain disease-modifying therapies for MS, particularly when they are discontinued or switched. Typically occurring within weeks to a few months after discontinuation, rebound effect may manifest as new or worsening relapses, increased gadolinium-enhancing lesions on MRI, and sometimes severe disability progression.

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