Phase 3 EMNERGIZE Trial Launches to Evaluate Empasiprubart in CIDP

Researchers recently detailed the design of the ongoing phase 3 EMNERGIZE trial, which is evaluating empasiprubart, an investigational complement C2 inhibitor, as a potential targeted treatment for adults with active chronic inflammatory demyelinating polyneuropathy (CIDP).¹

Presented at the 2026 Peripheral Nerve Society (PNS) Annual Meeting, held June 13-16 in Maastricht, Netherlands, the global, randomized, double-blind, placebo-controlled study (NCT07091630) is designed to assess the efficacy and safety of empasiprubart in approximately 160 adults with CIDP. Led by Simon Rinaldi, MRCP(Neuro), PhD, professor of neurology and honorary consultant neurologist at the University of Oxford, the trial began enrollment in September 2025 and is currently recruiting participants across multiple international sites.

For context, it is believed that complement activation may contribute to CIDP pathogenesis through immune-mediated nerve injury and macrophage-driven demyelination. Nerve biopsy studies have demonstrated complement deposition in affected nerves, providing a rationale for evaluating complement inhibition as a therapeutic strategy.²

The EMNERGIZE study will randomize participants in a 2:1 ratio to receive intravenous empasiprubart or placebo. During the double-blind portion of the trial, patients will receive doses on days 1 and 8 followed by administration every 4 weeks through week 24. Participants completing this phase will transition into a long-term extension period consisting of a 4-week blinded rollover phase followed by a 23-month open-label treatment period and a subsequent 15-month safety follow-up.¹

Eligible participants must meet 2021 European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) criteria for typical CIDP or selected CIDP variants, including motor, multifocal, focal, or distal forms of the disease. Investigators are enrolling patients with residual disability and evidence of active disease, including both treatment-naïve individuals and those willing to discontinue existing CIDP therapies before study entry.

The primary efficacy endpoint is the proportion of patients achieving at least a 1-point improvement from baseline on the adjusted Inflammatory Neuropathy Cause and Treatment (aINCAT) disability score at week 24. Key secondary endpoints include changes in Inflammatory Rasch-built Overall Disability Scale (I-RODS) scores, Medical Research Council Sum Score, dominant hand grip strength, Timed Up and Go performance, and time to a clinically meaningful improvement in aINCAT score.

CIDP is a chronic immune-mediated neuropathy characterized by progressive or relapsing weakness, sensory impairment, and functional disability resulting from peripheral nerve inflammation and demyelination. Although treatments such as intravenous immunoglobulin (IVIg), subcutaneous immunoglobulin (SCIg), corticosteroids, and plasma exchange remain standard therapies, many patients continue to experience residual disability, treatment burden, or disease activity despite available options.^3,4

The study enters an increasingly competitive CIDP treatment landscape. In 2024, the US Food and Drug Administration approved the FcRn blocker efgartigimod hyaluronidase-qvfc for adults with CIDP following positive results from the ADHERE trial, marking the first approved FcRn-targeted therapy for the disease.⁵ While FcRn blockade reduces circulating pathogenic IgG antibodies, empasiprubart targets a distinct immune pathway through complement inhibition.

Empasiprubart is a monoclonal antibody that targets complement component C2, thereby inhibiting activation of both the classical and lectin complement pathways. Unlike terminal complement inhibitors that act downstream in the cascade, C2 inhibition is intended to block upstream complement activation while preserving the alternative pathway, which may have implications for host immune defense. However, the clinical relevance of this approach in CIDP remains to be established.¹

Because EMNERGIZE is currently enrolling, no efficacy or safety data are yet available. As such, the trial primarily serves as an important test of whether complement inhibition can translate into meaningful clinical benefit for patients with CIDP. The results may also provide additional insight into the role of complement-mediated mechanisms in the disease's pathophysiology.

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REFERENCES
1. Rinaldi S, Brannagan T, Doneddu PE, et al. Empasiprubart Versus Placebo in Chronic Inflammatory Demyelinating Polyradiculoneuropathy: EMNERGIZEPhase 3 Study Design. Presented at: Peripheral Nerve Society (PNS) Annual Meeting; June 13-17, 2026; Maastricht, Netherlands.
2. Stettner M, Kieseier BC. Role of complement in immune-mediated neuropathies. J NeurolNeurosurg Psychiatry . 2023;94(2):112-119. Doi:10.1136/jnnp-2022-330277
3. Van den Bergh PYK, van Doorn PA, Hadden RDM, et al. European Academy of Neurology/Peripheral Nerve Society guideline on diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy. J PeripherNerv Syst . 2021;26(3):242-268. doi:10.1111/jns.12455
4. Mathey EK, Park SB, Hughes RAC, et al. Chronic inflammatory demyelinating polyradiculoneuropathy: from pathology to phenotype. J NeurolNeurosurg Psychiatry . 2015;86(9):973-985. https://jnnp.bmj.com/content/86/9/973
5. Howard JF Jr, Bril V, Burns TM, et al. Safety, efficacy, and tolerability of efgartigimod in chronic inflammatory demyelinating polyneuropathy (ADHERE). Lancet Neurol. 2024;23(10):1014-1026. Do: 10.1016/S1474-4422(24)00221-9