ANALYSIS LINKS INFLAMMATORY BIOMARKER TO NEUROMYELITIS OPTICA SPECTRUM DISORDER (NMOSD), REINFORCES EFFICACY OF UPLIZNA® (INEBILIZUMAB) IN REDUCING DISEASE-RELATED ATTACKS

ANALYSIS LINKS INFLAMMATORY BIOMARKER TO NEUROMYELITIS OPTICA SPECTRUM DISORDER (NMOSD), REINFORCES EFFICACY OF UPLIZNA^® (INEBILIZUMAB) IN REDUCING DISEASE-RELATED ATTACKS 

Data at ECTRIMS 2023 Demonstrate the Durable Efficacy of UPLIZNA in Reducing the Burden of Disease

THOUSAND OAKS, Calif. (Oct. 11, 2023) – Amgen (NASDAQ:AMGN) today announced the presentation of new analyses from the N-MOmentum clinical trial of UPLIZNA^®, offering clinically relevant insights on the peripheral presence of inflammatory biomarkers associated with NMOSD and reinforcing the effect of UPLIZNA in reducing disease-related attacks. These and other data, including long-term outcomes of UPLIZNA treatment, were presented this week during the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS 2023) in Milan, Italy. UPLIZNA is the first and only targeted CD19+ B-cell-depleting therapy approved in the United States, Europe and other geographies for the treatment of NMOSD in adults who are anti-aquaporin-4 immunoglobulin G seropositive (AQP4-IgG+).     

NMOSD is a chronic autoimmune disease characterised by recurrent acute attacks that can cause irreversible neurological damage and cumulative disability. Research has increasingly shown that tracking measurable biomarkers in the blood can provide clinically useful information about disease activity in a patient that can inform treatment plans. A presentation at ECTRIMS focuses on cytokines, small signaling proteins that are associated with inflammation throughout the body. While cytokine levels have been known to be elevated in various rheumatologic diseases, few studies have linked this important biomarker to disease activity in NMOSD.  

An analysis from the N-MOmentum study (NCT02200770) evaluated the relationship between cytokine levels and disease activity in NMOSD by evaluating protein markers from both treated and placebo group participants (n=211) at baseline and post treatment using immunoassay and biomarker panels, and correlating these levels to clinical endpoints over the course of the study. The analysis found significantly elevated levels in 18 of the 92 proteins measured at baseline, most notably IL-17a, which was elevated in approximately 60% of the participants, along with IL-6, IFN-y and CXCL10, which were elevated in approximately 20% of participants. Importantly, regardless of baseline cytokine levels, attack rates decreased among participants who received UPLIZNA throughout the open label period.  

“Peripheral cytokine levels provide important information about inflammatory reactions in the body. Tracking changes in cytokine levels for people with NMOSD shows potential clinical utility to understand the patho-immunology of disease,” said Bruce Cree, M.D., Ph.D., MAS, study author and professor of clinical neurology at the University of California San Francisco Weill Institute for Neurosciences. “These data show that UPLIZNA is effective in reducing disabling NMOSD attacks regardless of how inflammatory an individual’s baseline cytokine profile may be and underscore UPLIZNA’s effectiveness.”  

Long-term Outcomes Associated With UPLIZNA 

New findings from the N-MOmentum clinical trial presented at ECTRIMS reinforce the durable impact of UPLIZNA for people with NMOSD. Using data from the trial’s open-label extension period, this analysis compared the efficacy of UPLIZNA (n=208) to historical data from published NMOSD studies on outcomes with immunosuppressive therapies such as azathioprine (AZA/IST, n=132) and placebo (PBO, n=106). The analysis found that UPLIZNA significantly extended the time to onset of an NMOSD attack compared to reported data on AZA/IST or placebo (HR: 0.29 and 0.15, respectively). Further, UPLIZNA treatment provided a long-term attack-free survival benefit when compared to the relative timeframe reported with AZA/IST or PBO (77% for UPLIZNA treated participants vs. 36% for AZA/IST and 12% for PBO at 4 years). Notably, the time to attack for the PBO group in the trial’s randomized controlled period was similar to the historical group (HR=1.15), further validating the use of historical datasets for these types of analyses. 

“These data contribute to the growing body of evidence illustrating the significant and sustained impact of UPLIZNA for people with NMOSD, as evidenced by meaningful improvements in time to attack and attack-free survival,” said Kristina Patterson, M.D., Ph.D., senior medical director, neuroimmunology medical affairs, Amgen. “With continued long-term results reinforcing the favourable clinical profile of UPLIZNA, these data further support its ability to manage the effects of this challenging disease and reduce the risk of future attacks that could lead to irreversible disability.”  

About Neuromyelitis Optica Spectrum Disorder (NMOSD)

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.^1,2 Approximately 80% of all patients with NMOSD test positive for anti-AQP4 antibodies.3 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.⁴

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 CD19.⁵ 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.^4,6 Loss of vision, paralysis, loss of sensation, bladder and bowel dysfunction, nerve pain and respiratory failure can all be manifestations of the disease.⁷ Each NMOSD attack can lead to further cumulative damage and disability.^8,9 NMOSD occurs more commonly in women and may be more common in individuals of African and Asian descent.^10,11

About UPLIZNA

For information about UPLIZNA in Europe, please view the Summary of Product Characteristics.

About Amgen 
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.  

Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world's leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.  

Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average and is also part of the Nasdaq-100 index. In 2023, Amgen was named one of “America’s Greatest Workplaces” by Newsweek, one of “America’s Climate Leaders” by USA Today and one of the “World’s Best Companies” by TIME.

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References

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2. What is NMO? Accessed April 15, 2021. Guthyjacksonfoundation.org. 
   www.guthyjacksonfoundation.org/neuromyelitis-optica-nmo/ .
3. What We Know About NMO. Accessed Aug. 2, 2022. Sumairafoundation.org. 
   https://www.sumairafoundation.org/what-to-know-about-nmo/ 
4. Liu Y, et al. A tract-based diffusion study of cerebral white matter in neuromyelitis optica reveals widespread pathological alterations. Mult Scler. 2011;18(7):1013-1021.
5. Chihara N, et al. Interleukin 6 signaling promotes anti-aquaporin-4 autoantibody production from plasmablasts in neuromyelitis optica. PNAS. 2011;108(9):3701-3706.
6. Duan T, Smith AJ, Verkamn AS. Complement-independent bystander injury in AQP4-IgG seropositive neuromyelitis optica produced by antibody dependent cellular cytotoxicity. Acta Neuropathologica Comm. 2019;7(112).
7. Beekman J, et al. Neuromyelitis optica spectrum disorder: patient experience and quality of life. Neurol Neuroimmunol Neuroinflamm. 2019;6(4):e580.
8. Kimbrough DJ, et al. Treatment of neuromyelitis optica: review and recommendations. Mult Scler Relat Disord. 2012;1(4):180-187.
9. Baranello RJ, Avasarala, JR. Neuromyelitis optica spectrum disorders with and without aquaporin 4 antibody: Characterization, differential diagnosis, and recent advances. J Neuro Ther. 2015;1(1):9-14.
10. Wingerchuk DM. Neuromyelitis optica: effect of gender. J Neurol Sci. 2009;286(1-2):18-23.
11. Flanagan EP, et al. Epidemiology of aquaporin-4 autoimmunity and neuromyelitis optica spectrum. Ann Neurol. 2016;79(5):775-783.