RARE Daily

Horizon Reports New Analysis of MRI Findings of Uplinza in People with NMOSD

July 6, 2023

Rare Daily Staff

Horizon Therapeutics reported the presentation of a new analysis of MRI data from the phase 3 clinical trial of Uplinza showing a reduction in the formation of subclinical transverse myelitis lesions in people with NMOSD.

The analysis was presented at the 9th Congress of the European Academy of Neurology in Budapest.

NMOSD is a unifying term for neuromyelitis optica (NMO) and related syndromes. NMOSD is a rare, severe, relapsing, neuroinflammatory autoimmune disease that attacks the optic nerve, spinal cord, brain, and brain stem., Approximately 80 percent of all patients with NMOSD test positive for anti-AQP4 antibodies. AQP4-IgG binds primarily to astrocytes in the central nervous system and triggers an escalating immune response that results in lesion formation and astrocyte death.

Anti-AQP4 autoantibodies are produced by plasmablasts and some plasma cells. These B-cell populations are central to NMOSD disease pathogenesis, and a large proportion of these cells express CD19. Depletion of these CD19+ B cells is thought to remove an important contributor to inflammation, lesion formation and astrocyte damage. Clinically, this damage presents as an NMOSD attack, which can involve the optic nerve, spinal cord, and brain. Loss of vision, paralysis, loss of sensation, bladder and bowel dysfunction, nerve pain and respiratory failure can all be manifestations of the disease. Each NMOSD attack can lead to further cumulative damage and disability. NMOSD occurs more commonly in women and may be more common in individuals of African and Asian descent.

Uplinza is the first and only targeted CD19+ B-cell-depleting therapy approved by the U.S. Food and Drug Administration, the European Commission and the Brazilian Health Regulatory Agency for the treatment of NMOSD in adults who are anti-aquaporin-4 immunoglobulin G seropositive (AQP4-IgG+). The N-MOmentum pivotal trial is also the largest phase 3 clinical trial in NMOSD and the only phase 3 trial that collected MRI data, which were also incorporated into its attack adjudication criteria. Results from this post-hoc analysis demonstrate that Uplinza effectively reduced the formation of subclinical MRI lesions, while also showing an association between subclinical spinal cord lesions and future attacks.

During the trial, MRI imaging was conducted on the spinal cord, optic nerve and brain/brainstem to quantify the frequency, prognosis and response to treatment with Uplinza of subclinical lesions. This was taken at the time of screening, at the end of the 28-week randomized controlled period (RCP), at the time of any attack and annually during the open-label portion (OLP) of the trial. Of the 134 pivotal trial participants with full neuroaxis MRI and no new NMOSD symptoms at the end of the 28-week RCP, 20 (15 percent) were found to have asymptomatic MRI lesions on the spinal cord. These lesions were shorter than attack-associated lesions, and importantly were less frequent among those receiving UPLIZNA.

Subsequent MRI findings showed that the formation of these lesions decreased as treatment with Uplinza continued. Interestingly, these findings showed that subclinical lesions were associated with domain-specific attacks in the following year.

“Attack prevention is a priority in managing NMOSD, as just one attack can lead to life-altering vision loss and mobility challenges,” said Kristina Patterson, senior medical director, neuroimmunology medical affairs, Horizon. “We are pleased to see that the long-term phase 3 pivotal trial data show that Uplinza effectively reduced subclinical MRI findings and NMOSD attacks while continuing to offer new learnings that help advance our understanding of the disease and improve patient care.”

Photo: Kristina Patterson, senior medical director, neuroimmunology medical affairs, Horizon


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