Analysis: Uplizna Provides Long-term NMOSD Attack Prevention
Uplizna (inebilizumab-cdon) safely prevented autoimmune attacks in 83% of people with neuromyelitis optica spectrum disorder (NMOSD) who received the treatment for four or more years, data from the N-MOmentum Phase 2/3 clinical trial show.
Among those who experienced relapses, most did so during the first year of treatment. Beyond one year, 92% remained attack-free with no new safety concerns.
“This long-term study is important because NMOSD is a chronic disease that requires lifelong management. Physicians need to understand the implications of prolonged treatment,” Bruce Cree, MD, PhD, principal investigator of N-MOmentum, said in a press release. Cree is a professor at the University of California San Francisco Weill Institute for Neurosciences.
Findings from the study, “Long-term efficacy and safety of inebilizumab in neuromyelitis optica spectrum disorder: Analysis of aquaporin-4–immunoglobulin G–seropositive participants taking inebilizumab for ⩾4 years in the N-MOmentum trial,” were published in the Multiple Sclerosis Journal.
Uplizna is a treatment that depletes antibody-producing B-cells, which contribute to altered immune (autoimmune) attacks against neuron-supporting cells in people with NMOSD, causing inflammation in the optic nerve and spinal cord.
The therapy is approved for adults who test positive for antibodies against aquaporin-4 water channel (AQP4), the most common target of NMOSD-related antibodies, and aims to lower the risk of relapse among patients by lowering antibody production.
Uplizna’s approval was based on positive safety and efficacy data from the N-MOmentum trial (NCT02200770), in which participants received 300 mg of Uplizna (174 patients) or a placebo (56 patients) via into-the-vein infusion on days 1 and 15, and then were followed for about 6.5 months.
After this period, 201 participants entered an ongoing open-label extension (OLE) study and continued receiving 300 mg Uplizna every 6.5 months to evaluate its long-term impact.
The recent analysis focused on the efficacy and safety of Uplizna treatment in 75 patients who have been receiving the therapy for four or more years, in N-MOmentum and the OLE. The findings were reported by researchers at the Cleveland Clinic and the University of Cincinnati in Ohio, in collaboration with scientists at Horizon Therapeutics, the company that markets the therapy.
Most of these patients were women (93%) and younger than 65 (99%), and 10 patients had been given a placebo initially during N-MOmentum. Over the two years prior to Uplizna treatment, the annualized attack rate (AAR) among these patients was 1.8 attacks per person-year.
In this group, a total of 18 attacks occurred in 13 patients after the first dose, which equaled an AAR of 0.052 attacks per person-year. Overall, most of these attacks (67%) occurred within the first year of treatment. Of the five attacks that were considered major in severity, all but one occurred during the first year of treatment.
Over four or more years of Uplizna treatment, 62 (83%) patients did not experience an attack. Beyond one year of therapy, 69 (92%) were attack-free during follow-up. Three patients had their first attacks after one year.
Statistical analysis demonstrated the attack-free probability was 87% after one year and remained stable during the follow-up years.
As designed, Uplizna depleted B-cells over four or more years, regardless of whether patients initially had received Uplizna or placebo in the N-MOmentum study.
Participants’ disability, as measured by the Expanded Disability Status Scale (EDSS), also remained stable for four years or more and the median EDSS change from pre-treatment throughout follow-up was 0.5 or less.
“It is highly encouraging to see that most patients in this study were attack-free after the first year of Uplizna treatment,” said Cree. “The data demonstrate that long-term Uplizna use is associated with a reduced risk of NMOSD attacks — possibly due to the depth and extent of B-cell depletion with repeated doses.”
Regarding safety, 93% of participants reported treatment-emergent adverse effects (TEAEs), with 39% experiencing one or more TEAEs considered related to Uplizna. Two participants (3%) had a serious TEAE related to treatment, and four (5%) temporarily stopped treatment after one or more TEAE. No discontinuations or deaths were reported.
Of the 866 total Uplizna infusions, a total of 27 (3%) infusion-related adverse events were reported, with dose interruptions due to these reactions occurring in three participants.
Infections were reported in 59 patients (79%), and were mostly mild or moderate, but the infection rate or severity did not increase over four or more years of treatment. Pneumonia was the only serious infection occurring in two participants, and life-threatening pneumonia and urinary tract infection were reported in one individual.
“These results from the N-MOmentum study continue to support use of [Uplizna] for treatment of neuromyelitis optica spectrum disorder,” the researchers concluded. “Furthermore, the findings suggest that efficacy of [Uplizna] may be enhanced after the first year of treatment, warranting additional long-term investigation.”
“NMOSD is a complex and often unpredictable B-cell-mediated disease that presents significant challenges to both patients and physicians,” said Kristina Patterson, MD, PhD, medical director at Horizon. “With recent treatment advancements, the NMOSD community now has more options than ever before — including Uplizna, which is engineered for broad, deep and durable B-cell depletion.”
“We are fully committed to increasing our understanding of this disease so we can continue to improve patient care,” Patterson added.