Uplizna cuts NMOSD relapse risk, even after using immunosuppressants
New analysis backs approved therapy as both first-line, long-term choice
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Use of the approved therapy Uplizna (inebilizumab) reduces the risk of relapse and worsening disability in people with neuromyelitis optica spectrum disorder (NMOSD), regardless of whether patients had previously received conventional immunosuppressive treatments.
These are the findings of a post-hoc analysis of data from the Phase 2/3 N-MOmentum clinical trial (NCT02200770), whose top-line results had supported approval of the infusion therapy for NMOSD. Post-hoc analyses are those specified and performed after a trial is complete; in this case, N-MOmentum wrapped up in 2020.
The new analysis showed Uplizna lowered the risk of relapse for people with NMOSD by more than 70% compared with immunosuppressants (ISTs). Estimates also showed that patients using the therapy instead of ISTs were likely, by an even greater percentage, to remain attack-free at four years.
“These results generally support [Uplizna] treatment for patients with NMOSD regardless of previous first-line treatment with ISTs [immunosuppressants],” the researchers wrote.
The findings were published as a brief communication, titled “Efficacy of Inebilizumab in N-MOmentum Trial Participants With or Without Prior Immunosuppressants,” in the journal Annals of Clinical and Translational Neurology. The study was funded by Amgen, which markets Uplizna in North America and Europe. Three of the 10 study authors work for the company.
NMOSD is an autoimmune disease characterized by inflammation and damage to the optic nerves, which carry visual signals between the eyes and the brain, and the spinal cord. Most patients have self-reactive antibodies that target aquaporin-4 (AQP4), a water-channel protein present in neuron-supporting cells.
Conventional, oral immunosuppressive therapies, including azathioprine, mycophenolate mofetil, and methotrexate, have historically been used off-label for the treatment of NMOSD. However, approved antibody-based therapies, such as Uplizna, appear to have more favorable safety and efficacy profiles, according to the researchers.
Researchers go back to trial data supporting Uplizna’s approval
Uplizna is designed to kill B-cells, the immune cells that produce antibodies, by binding to and blocking CD19, a protein found at the surface of B-cells.
Its regulatory approvals were supported mainly by data from the 5.5-year N-Momentum trial, which tested Uplizna against a placebo in more than 200 adults with NMOSD.
Participants had a history of relapses, or periods when inflammatory attacks caused new or worsening symptoms. All were randomly assigned to receive Uplizna or a placebo on days 1 and 15 and followed for six months. After completing the placebo-controlled part of the trial, patients could enter an open-label extension in which all received the therapy every six months for up to three years.
The trial results showed that Uplizna significantly reduced the risk of relapses and disability worsening in NMOSD patients with anti-AQP4 antibodies.
Now, an international team of scientists noted that “many participants in N-MOmentum had a history of IST use, which could potentially impact the efficacy and safety of [Uplizna].”
That led the team to go back and take another look, conducting an analysis of trial data.
Altogether, their review covered 202 participants with anti-AQP4 antibodies, with a mean age of approximately 43. More than 90% were women, and 96, or nearly half, had been previously treated with conventional ISTs. These individuals were dubbed the IST group. Conventional immunosuppressants used by these patients included azathioprine, mycophenolate mofetil, and methotrexate.
The 106 participants who had not received such therapies were labeled the non-IST group.
Analysis shows approved therapy bests immunosuppressant use
The new results showed that, during the trial’s placebo-controlled part, Uplizna was associated with a significantly lower risk of relapse relative to the placebo, by 79% in the IST group and 77% in the non-IST group.
The therapy was also linked to a lower proportion of participants experiencing hospitalizations, regardless of prior IST history. A significantly lower proportion of Uplizna-treated patients experienced worsening disability, as assessed by the Expanded Disability Status Scale (EDSS), both in the IST group (19% vs. 44%) and in the non-IST group (14% vs. 28%).
Long-term data showed that regardless of IST history, Uplizna was associated with a high probability of patients remaining attack-free for 5.5 years or longer. The treatment also resulted in a reduction of the EDSS score, reflecting less disability, in both groups.
To compare the long-term efficacy of Uplizna with that of conventional immunosuppressants or a placebo, the researchers conducted indirect comparisons using data from N-MOmentum and previously published studies that assessed the effectiveness of azathioprine and other conventional ISTs.
The team found that Uplizna was significantly associated with a lower risk of relapse, by 71% relative to conventional ISTs and by 85% relative to the placebo. Models also estimated that, at four years, patients treated with Uplizna were more likely to remain free from relapses (77%) than those given conventional ISTs (36%) and those on a placebo (12%).
“Based on modeling data, [Uplizna] had greater long-term efficacy than historical immunosuppressants,” the researchers wrote.
This analysis demonstrates … that [Uplizna] has sustained long-term efficacy in reducing the risk of NMOSD attack regardless of prior … treatment.
Uplizna was generally well tolerated in participants with and without prior IST use. The most common adverse events during the N-Momentum’s extension portion were infections, affecting more than 72% of participants, and infusion-related reactions, experienced by about 12%. Overall, adverse events were more frequent in participants who had not received previous ISTs than among those who had.
“This analysis demonstrates that the efficacy of [Uplizna] is not influenced by prior IST use and that [Uplizna] has sustained long-term efficacy in reducing the risk of NMOSD attack regardless of prior … treatment,” the researchers wrote.
