Inebilizumab-Cdon Reduces Risk of IgG4-Related Disease Flares By 87% In Adult Patients

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Positive topline results from the MITIGATE phase 3 clinical trial (NCT04540497) demonstrate that inebilizumab-cdon (Uplizna; Viela Bio Inc) met its primary end point in patients with immunoglobulin G4-related disease (IgG4-RD). When studying the efficacy and safety of inebilizumab, the treatment was observed to reduce the risk of IgG4-RD flare by approximately 87%.¹

Inebilizumab is a monoclonal antibody and is currently indicated for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive. IgG4-RD is a chronic, systemic, immune-mediated, fibroinflammatory disease that can, generally, affect multiple organs in the body. Because it is a progressive disease that affects new organs over time—either consecutively or simultaneously—it is characterized by periods of remission as well as unpredictable disease flares. The disease can cause irreversible organ damage with or without the presence of symptoms. B cells are thought to drive the inflammatory and fibrotic processes that can contribute to disease activity, and inebilizumab is able to deplete B cells.^1,2

"IgG4-RD is a devastating, chronic, immune-mediated disease that has just begun to be fully understood over the last few decades," said principal investigator John Stone, MD, MPH, professor of medicine at Harvard Medical School and the Edward A Fox Chair in medicine at Massachusetts General Hospital, in a news release.¹

MITIGATE is a randomized, double-blind, placebo-controlled, parallel-group, multicenter phase 3 trial that is evaluating the efficacy and safety of inebilizumab when treating adult patients with IgG4-RD compared with placebo. According to the investigators, MITIGATE is the first randomized, double-blind, placebo-controlled trial of any treatment method to be conducted in patients with IgG4-RD.^1-3

The trial enrolled and randomly assigned 135 patients who received either 300 mg of inebilizumab or placebo, both of which were administered intravenously. Treatments were administered on days 1, 15, and week 26 following premedication, and patients were followed for a 52-week randomized control period. Additionally, the trial includes an optional 3-year open-label treatment period as well as a follow-up period after up to 2 years of inebilizumab to assess safety.^1,2

The primary end point was time to first treated and adjudicated flare due to IgG4-RD, which was defined as the time in days from day 1 to the date of the first treated IgG4-RD flare during the 52-week period. Secondary end points include annualized flare rate, flare-free and treatment-free complete remission, flare-free and corticosteroid-free complete remission, quality of life measures, and cumulative glucocorticoid use.^1-3

According to the findings, inebilizumab met its primary end point and showed a statistically significant reduction of about 87% in the risk of IgG4-RD flares compared with placebo during the placebo-controlled period (HR: 0.13, p < .0001). Additionally, the investigators noted that all key secondary end points—annualized flare rate, flare-free and treatment-free complete remission, as well as flare-free and corticosteroid-free complete remission—were met.¹

"MITIGATE is a landmark study with results that demonstrate an important advance in the treatment of patients with IgG4-RD, a devastating and rare disease that currently has no approved therapy," said Jay Bradner, MD, executive vice president of Research and Development and chief scientific officer at Amgen, in the news release. "We are grateful for the partnership with patients, clinicians and patient advocacy groups critical to a successful study, and we look forward to bringing this therapy to those living with IgG4-RD."¹

The authors noted that no new safety signals were observed during the trial, and the overall safety results of inebilizumab during the placebo-controlled period of the trial were consistent with the known safety profile. The most common adverse events reported by patients who were treated with inebilizumab in a previous trial for neuromyelitis optica spectrum disorder were infections, and included urinary tract infection and arthralgia. The investigators recommend that inebilizumab administration should be suspended for patients with an active infection and until it is resolved.¹

"These data mark a major milestone for the IgG4-RD community and provide substantial insight into not only how inebilizumab can help manage IgG4-RD, but also key insights into the nature of this condition," said Stone in the news release.¹

References

1. Amgen. Amgen Announces Positive Results For Phase 3 Registrational Trial Evaluating Uplizna (Inebilizumab-cdon) For Treatment of Immunoglobulin G4-Related Disease (IgG4-RD). News release. June 5, 2024. Accessed June 5, 2024. https://www.amgen.com/newsroom/press-releases/2024/06/amgen-announces-positive-results-for-phase-3-registrational-trial-evaluating-uplizna-inebilizumabcdon-for-treatment-of-immunoglobulin-g4related-disease-igg4rd

2. A Study of Inebilizumab Efficacy and Safety in IgG4-Related Disease. ClinicalTrials.gov identifier: NCT04540497. Updated May 7, 2024. Accessed June 5, 2024. https://clinicaltrials.gov/study/NCT04540497?cond=IgG4-Related%20Disease&intr=Inebilizumab&rank=1#study-overview

3. Perugino, C, Culver, EL, Khosroshahi, A, et al. Efficacy and Safety of Inebilizumab in IgG4-Related Disease: Protocol for a Randomized Controlled Trial. Rheumatol Ther. 2023;10(6):1795-1808. doi:10.1007/s40744-023-00593-7