Benzinga | Oct 13, 2021 01:38PM EDT

Horizon Therapeutics Reports Results From New Analysis Of UPLIZNA Phase 2/3 Trial Showing A Correlation Between Depth Of B-Cell Depletion, Improved Neuromyelitis Optica Spectrum Disorder Patient Outcomes

-- Findings presented at ECTRIMS 2021 suggest that deep, persistent B-cell depletion is linked to reduced disease activity --

Horizon Therapeutics plc (NASDAQ:HZNP) today announced results from a new analysis of the UPLIZNA pivotal Phase 2/3 N-MOmentum trial indicating a correlation between the depth of B-cell depletion and improved NMOSD patient outcomes. The data are being presented at the virtual 37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS 2021). UPLIZNA is the first and only FDA-approved anti-CD19 B-cell-depleting humanized monoclonal antibody for the treatment of adult patients with anti-aquaporin-4 (AQP4) antibody positive NMOSD.

"This analysis provides additional evidence that B cells play a central role in NMOSD, and that there is a link between the depth of B cell depletion in the blood and long-term clinical outcomes," said Jeffrey Bennett, M.D., Ph.D., University of Colorado and study author. "We found that B-cell levels at the end of the 28-week randomized, placebo-controlled period of the N-MOmentum trial were predictive of stable and deep B-cell depletion continuing through long-term exposure."

The N-MOmentum trial included a randomized-controlled period (RCP) of up to 28 weeks, followed by an optional open-label period (OLP) of at least two years. During the trial, B-cell counts were determined using high-resolution flow cytometry (captured as cells/?L). Disease activity was measured using annualized attack rate (AAR) and the number of new or enlarging T2 lesions in the brain or spine.

Key analysis findings include (P028):

* All participants had B-cell reductions at one week from first treatment.

* At Week 4 of the RCP, median (interquartile range [IQR]) B-cell counts were 2.5 (1.0--7.6) cells/?L in the inebilizumab group and 112.3 (96.3--176.9) cells/?L in the placebo group.

* At Week 156 of the OLP, median (IQR) B-cell count was 0.33 (< LLoQ--1.0) cells/?L with inebilizumab.

* UPLIZNA provided sustained B-cell depletion after 2.5 years and decreased NMOSD activity in treated patients, with a 97% reduction in AAR and a 73% reduction in new/enlarging lesions when compared to the placebo group.

* Participants with B-cell counts ? 4 cells/?L had persistently deeper B-cell depletion compared with those with B-cell counts > 4 cells/?L

* While all participants saw significant treatment effect, those whose B-cell counts were ? 4 cells/?L (n=139/200) at Week 28 had reduced rates of AAR (rate ratio 0.4) and new/enlarging lesions (0.36) versus those with B-cell counts > 4 cells/?L.

"These data contribute to our mechanistic understanding of NMOSD as a B-cell-mediated disease and provide greater evidence that UPLIZNA is working directly against those underlying disease mechanisms known to have the greatest impact on patient outcomes," said Quinn Dinh, M.D., vice president, international medical affairs and pipeline launch strategy for Horizon. "Our ongoing research efforts in this area aim to improve care for patients today while also preventing the damage of NMOSD over time."