Uplizna Safe, Effective in NMOSD Patients Given Rituximab, Data Show

Yedida Y Bogachkov PhD avatar

by Yedida Y Bogachkov PhD |

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Prior treatment with rituximab does not limit the effectiveness or safety of Uplizna (inebilizumab-cdon) in people with  neuromyelitis optica spectrum disorder (NMOSD), a further analysis of data from the N-MOmentum Phase 2/3 trial has found.

Uplizna’s efficacy in preventing NMOSD attacks and its safety profile were comparable in trial patients both with and without prior exposure to rituximab, frequently used off-label to treat NMOSD, the researchers found. Both therapies work by targeting B-cells, a type of immune cell.

“Physicians who are considering transitioning their patients from rituximab to Uplizna are eager for evidence that this can be done safely and effectively,” Kristina Patterson, MD, PhD, medical director, neuroimmunology at Horizon Therapeutics , said in a press release.

These findings were in the study “Inebilizumab for treatment of neuromyelitis optica spectrum disorder in patients with prior rituximab use from the N-MOmentum Study,” published in the journal Multiple Sclerosis and Related Disorders.

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European Committee Favors Uplizna’s Approval for Certain Adults With NMOSD

Uplizna was approved by the U.S. Food and Drug Administration (FDA) in June 2020 to treat adult patients who test positive for antibodies against aquaporin-4 protein (AQP4), the most common target of NMOSD-related antibodies. Its approval was supported by data from the N-MOmentum trial (NCT02200770), which tested Uplizna against placebo in 230 adults.

Trial results showed Uplizna to safely and sustainably reduce the frequency of attacks in NMOSD patients, whose episodes of inflammation can affect vision and muscle control.

Both rituximab and Uplizna have similar mechanisms of action, in which immune B-cells are targeted and eliminated depending on the proteins expressed on their surfaces. B-cell depletion reduces their antibody production to prevent NMOSD attacks.

Rituximab — which is not FDA approved to treat NMOSD, although off-label use has been common — targets CD-20 proteins on the surface of B-cells, whereas Uplizna targets CD-19 proteins.

“Because of their closely related mechanisms of action, consideration as to whether inebilizumab may be a suitable treatment option for patients with prior rituximab experience is important,” the researchers wrote.

Scientists at Horizon and institutes across the U.S. analyzed post-hoc data on 17 N-MOmentum patients who had prior rituximab use. Among other reasons, patients reported discontinuing rituximab due to ongoing disease activity despite treatment.

Among these 17 people, 13 were randomly assigned in the trial to Uplizna treatment, and the other four to a placebo.

Seven of the 13 Uplizna-treated patients had breakthrough attacks prior to enrollment in the study despite rituximab’s use — an annualized attack rate of 0.78 attacks per person-year. No NMOSD attacks were reported in these seven patients while they were on Uplizna.

“It is encouraging to see that in this analysis, none of the seven patients who experienced breakthrough attacks while previously being treated with rituximab went on to experience an attack while taking Uplizna,” said Eoin P. Flanagan, a neurologist with the Mayo Clinic and the study’s lead author.

“Although Uplizna and rituximab both target B cells, Uplizna targets a broader range of B cells, and may explain why patients in the study who had attacks while being treated with rituximab did not experience attacks with Uplizna,” Flanagan added.

One of the 13 Uplizna-group patients had an attack while on this therapy. Two NMOSD attacks were also reported in two other patients (one attack each), both assigned in the main trial to a placebo, during the study’s open-label extension in which all are given Uplizna.

These three attacks were myelitis, inflammation of the spinal cord, and were graded as mild, the study noted.

The overall annualized attack rate of those with prior exposure to rituximab was 0.08 attacks/person-year, which was similar to the annualized attack rate of participants with no prior rituximab use (0.10 attacks/person-year), the scientists reported.

Secondary outcomes — including changes from the study’s start (baseline) in expanded disability status scale scores (a measure of disability), number of active lesions on MRI, and number of NMOSD-related hospital stays — were similar in the two groups.

Uplizna had a generally similar safety profile in patients with and without prior rituximab use, with similar rates of treatment-related side effects and infusion-related reactions. Infections were reported in nearly all participants (94%) with prior rituximab use, emphasizing a need for clinical vigilance with these patients.

Overall, “this analysis may suggest that appropriate patients can successfully transition from rituximab to Uplizna, which is particularly important for physicians who have been hesitant to transition patients to a different medicine because they don’t want to trigger an attack,” Patterson said.

Further studies, however, are needed to “determine potential safety concerns of inebilizumab [Uplizna], including risk of infection, in rituximab-experienced patients,” the scientists added.